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Traditional Chinese medicine is a resource for drug discovery against 2019 novel coronavirus (SARS-CoV-2)
Chang-quan Ling
Journal of Integrative Medicine    2020, 18 (2): 87-88.   DOI: 10.1016/j.joim.2020.02.004
Accepted: 13 February 2020
Online available: 14 February 2020

Abstract1419)   HTML    PDF      
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Effectiveness and safety of acupuncture for treating functional constipation: An overview of systematic reviews
Jun-peng Yao, Li-ping Chen, Xian-jun Xiao, Ting-hui Hou, Si-yuan Zhou, Ming-min Xu, Kai Wang, Yu-jun Hou, Lin Zhang, Ying Li
Journal of Integrative Medicine    2022, 20 (1): 13-25.   DOI: 10.1016/j.joim.2021.11.001
Online available: 16 November 2021

Abstract1254)   HTML    PDF      

Background

Functional constipation (FC) is one of the most prevalent functional gastrointestinal disorders. Dissatisfaction with medications prescribed to treat FC may lead patients to seek alternative treatments. Numerous systematic reviews (SRs) examining the use of acupuncture to treat FC have reported inconsistent results, and the quality of these studies has not been fully evaluated.

Objective

In this overview, we evaluated and summarized clinical evidence on the effectiveness and safety of acupuncture for treating FC and evaluated the quality and bias of the SRs we reviewed.

Search strategy

The search strategy was structured by medical subject headings and search terms such as “acupuncture therapy” and “functional constipation.” Electronic searches were conducted in eight databases from their inception to September 2020.

Inclusion criteria

SRs that investigated the effectiveness and safety of acupuncture for managing FC were included.

Data extraction and analysis

Two authors independently extracted information and appraised the methodology, reporting accuracy, quality of evidence, and risk of bias using the following critical appraisal tools: (1) A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2); (2) Risk of Bias in Systematic Reviews (ROBIS); (3) Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A); and (4) the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). A κ index was used to score the level of agreement between the 2 reviewers.

Results

Thirteen SRs that examined the clinical utility of acupuncture for treating FC were identified. Using the AMSTAR 2 tool, we rated 92.3% (12/13) of the SRs as “critically low” confidence and one study as “low” confidence. Using the ROBIS criteria, 38.5% (5/13) of the SRs were considered to have “low risk” of bias. Based on PRISMA-A, 76.9% (10/13) of the SRs had over 70% compliance with reporting standards. The inter-rater agreement was good for AMSTAR 2, ROBIS, and PRISMA-A. Using the GRADE tool, we classified 22.5% (9/40) of the measured outcomes as “moderate” quality, 57.5% (23/40) as “low” quality, and 20.0% (8/40) as “very low” quality. The inter-rater agreement was moderate when using GRADE. Descriptive analyses indicated that acupuncture was more efficacious than sham acupuncture for improving weekly complete spontaneous bowel movements (CSBMs) and for raising the Bristol Stool Form Scale (BSFS) score. Acupuncture appeared to be superior to anti-constipation drugs for improving weekly spontaneous bowel movements, the total effective rate, and the Patient Assessment of Constipation Quality of Life score. Although ten SRs mentioned the occurrence of adverse events, serious adverse events were not associated with acupuncture treatment.

Conclusion

Acupuncture may be more efficacious than sham acupuncture for improving CSBMs and BSFS scores and may be superior to anti-constipation drugs for improving bowel movement frequency, as well as quality of life. Limitations to current studies and inconsistent evidence suggest a need for more rigorous and methodologically sound SRs to draw definitive conclusions.

Systematic review registration

PROSPERO CRD42020189173.

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In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus
Deng-hai Zhang, Kun-lun Wu, Xue Zhang, Sheng-qiong Deng, Bin Peng
Journal of Integrative Medicine    2020, 18 (2): 152-158.   DOI: 10.1016/j.joim.2020.02.005
Accepted: 13 February 2020
Online available: 14 February 2020

Abstract851)   HTML    PDF      

Objective:

In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus (2019-nCoV), an ongoing novel coronavirus that causes pneumonia.

Methods

There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database. Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV interaction. In the second step we searched Chinese herbal databases to identify treatments containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb.

Results

Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these 26 treatments were related to regulating viral infection, immune/inflammation reactions and hypoxia response.

Conclusion

Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.

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Active constituents and mechanisms of Respiratory Detox Shot, a traditional Chinese medicine prescription, for COVID-19 control and prevention: network-molecular docking-LC-MSE analysis
Zi-jia Zhang, Wen-yong Wu, Jin-jun Hou, Lin-lin Zhang, Fei-fei Li, Lei Gao, Xing-dong Wu, Jing-ying Shi, Rong Zhang, Hua-li Long, Min Lei, Wan-ying Wu, De-an Guo, Kai-xian Chen, Lewis A. Hofmann, Zhonghua Ci
Journal of Integrative Medicine    2020, 18 (3): 229-241.   DOI: 10.1016/j.joim.2020.03.004
Accepted: 17 March 2020
Online available: 20 March 2020

Abstract837)   HTML    PDF      

Objective 

The Lung-toxin Dispelling Formula No.1 (referred to as Respiratory Detox Shot, RDS) was established based on the theory of traditional Chinese medicine (TCM) medicinal properties and the classical prescription of TCM. It has demonstrated therapeutic benefits in both disease control and prevention in the effort to contain corona virus disease 2019 (COVID-19). However, the material basis and action mechanism of RDS are still unclear. The goal of the study is to clarify the material foundation and action mechanism of RDS.

Methods 

To achieve in-depth analyses of RDS from a holistic perspective, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, cluster analysis, and the hub genes involved in the disease pathways were identified, and their corresponding compounds were further applied to molecular docking for in vitro biological validation. The presence of the validated compounds was also measured to demonstrate the material basis of RDS. In our network pharmacology study, a total of 26 bioinformatic software and databases were accessed, and 6 networks covering the entire Zang-fu viscera were constructed to achieve comprehensive analysis and visualization of the intricate connections among the compounds-targets-disease pathway-meridians of RDS.

Results 

For all 1071 compounds of 9 ingredients of RDS from established TCM databases, 157 compounds passed drug-likeness screening and led to 339 predicted targets in the compound-target network. 42 hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-compound-disease network. Twelve disease pathways attributed to Lung-Large intestine meridian, with 6 and 5 to Kidney-Urinary bladder and Stomach-Spleen meridians, respectively. 118 candidate compounds showed a high binding affinity with SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) by molecular docking using computational pattern recognition. The in vitro activity of 22 compounds was validated by the 3CLpro inhibition assay. Finally, using the technique of liquid chromatography mass spectrometry in data-independent analysis mode, 7 out of 22 compounds were confirmed and validated in RDS aqueous decoction with reference standards in both non-targeted and targeted approaches.

Conclusion 

Our results unveiled that RDS acts primarily in the Lung-Large intestine, Kidney-Urinary bladder, and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all 9 ingredients. Integrated with the context of TCM meridian theory, multiple components and targets of RDS demonstrate the action dual effects of health-strengthening and pathogen-eliminating in one prescription to achieve systemic therapeutic effects for early COVID-19 control and prevention.

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Chinese herbal medicine for COVID-19: Current evidence with systematic review and meta-analysis
Arthur Yin Fan, Sherman Gu, Sarah Faggert Alemi, Research Group for Evidence-based Chinese Medicine
Journal of Integrative Medicine    2020, 18 (5): 385-394.   DOI: 10.1016/j.joim.2020.07.008
Accepted: 28 June 2020
Online available: 06 July 2020

Abstract664)   HTML    PDF      

Background
There is currently no drug or therapy that cures COVID-19, a highly contagious and life-threatening disease.
Objective
This systematic review and meta-analysis summarized contemporary studies that report the use of Chinese herbal medicine (CHM) to treat COVID-19.
Search strategy: Six electronic databases (PubMed/MEDLINE, Cochrane Library, ScienceDirect, Google Scholar, Wanfang Data and China National Knowledge Infrastructure) were searched from their beginning to May 15, 2020 with the following search terms: traditional Chinese medicine, Chinese medicine, Chinese herbal medicine, COVID-19, new coronavirus pneumonia, SARS-CoV-2, and randomized controlled trial.
Inclusion criteria: Randomized controlled trials (RCTs) from peer-reviewed journals and non-reviewed publications were included. Further, included RCTs had a control group that was given standard care (SC; such as conventional Western medicine treatments or routine medical care), and a treatment group that was given SC plus CHM.
Data extraction and analysis: Two evaluators screened and collected literature independently; information on participants, study design, interventions, follow-up and adverse events were extracted, and risk of bias was assessed. The primary outcomes included scores that represented changes in symptoms and signs over the course of treatment. Secondary outcomes included the level of inflammatory markers, improvement of pneumonia confirmed by computed tomography (CT), and adverse events. Dichotomous data were expressed as risk ratio or hazard ratio with 95% confidence interval (CI); where time-to-event analysis was used, outcomes were expressed as odds ratio with 95% CI. Continuous data were expressed as difference in means (MD) with 95% CI, and standardized mean difference (SMD) was used when different outcome scales were pooled.
Results
Seven original studies, comprising a total of 732 adults, were included in this meta-analysis. Compared to SC alone, CHM plus SC had a superior effect on the change of symptom and sign score (–1.30 by SMD, 95% CI [–2.43, –0.16]; 3 studies; n = 261, P = 0.03), on inflammatory marker C-reactive protein (CRP, mg/L; –11.82 by MD, 95% CI [–17.95, –5.69]; 5 studies; n = 325, P = 0.0002), on number of patients with improved lung CT scans (1.34 by risk ratio, 95% CI [1.19, 1.51]; 4 studies; n = 489, P < 0.00001). No significant adverse events were recorded in the included RCTs.


Conclusion
Current evidence shows that CHM, as an adjunct treatment with standard care, helps to improve treatment outcomes in COVID-19 cases.

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Diagnosis and treatment of novel coronavirus infectious pneumonia based on the theory of traditional Chinese medicine
Shi-xin Wang, Yan Wang, Yu-bao Lu, Jie-yun Li, Yu-jun Song, Munkhtuya Nyamgerelt, Xue-xi Wang
Journal of Integrative Medicine    2020, 18 (4): 275-283.   DOI: 10.1016/j.joim.2020.04.001
Accepted: 20 March 2020
Online available: 20 March 2020

Abstract641)   HTML    PDF      
Since the outbreak of coronavirus disease-19 (COVID-19) in Wuhan in December 2019, it has rapidly spread to the whole country and the world, causing serious harm to the health of people and a huge social burden. However, currently, there are no clinically available drugs, except for vaccines against COVID-19 that are being evaluated. Traditional Chinese medicine (TCM) is capable of performing syndrome differentiation and treatment according to the clinical manifestations of patients, and has a better ability of epidemic prevention and control. Therefore, we comprehensively analyzed the etiology and pathogenesis of COVID-19 based on the theory of TCM, and discussed its syndrome differentiation, treatment, and prevention measures to provide strategies and reference for the prevention and treatment of COVID-19 with TCM.
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Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by reducing expression of androgen receptor and 5α-reductase in a rat model
Tian Fang, Ze-sheng Xue, Jia-xuan Li, Jia-kuan Liu, Di Wu, Mei-qian Li, Yu-ting Song, Shi-feng Yun, Jun Yan
Journal of Integrative Medicine    2021, 19 (3): 258-264.   DOI: 10.1016/j.joim.2020.12.002
Online available: 10 December 2020

Abstract586)   HTML    PDF      
Objective
Herbal medicine is an important therapeutic option for benign prostatic hyperplasia (BPH), a common disease in older men that can seriously affect their quality of life. Currently, it is crucial to develop agents with strong efficacy and few side effects. Herein we investigated the effects of the extract of Rauwolfia vomitoria, a shrub grown in West Africa, on BPH.
Methods
Rats with testosterone-induced BPH were treated with R. vomitoria. Prostates were histologically analyzed by hematoxylin and eosin staining. Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting. Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction. The sperm count and body weight of rats were also measured.
Results
The oral administration of R. vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats, supported by the decreased thickness of the prostate epithelial layer and increased lumen size. Similar effects were observed in the BPH rats treated with the reference drug, finasteride. R. vomitoria extract significantly reduced the testosterone-induced proliferation markers, including proliferating cell nuclear antigen and cyclin D1, in the prostate glands of BPH rats; it also reduced levels of androgen receptor, its associated protein steroid 5α-reductase 1 and its downstream target genes (FK506-binding protein 5 and matrix metalloproteinase 2). Notably, compared with the finasteride group, R. vomitoria extract did not significantly reduce sperm count. 
Conclusion
R. vomitoria suppresses testosterone-induced BPH development. Due to its milder side effects, R. vomitoria could be a promising therapeutic agent for BPH.
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Using weighted blankets in an inpatient mental health hospital to decrease anxiety
Annette L. Becklund, Lisa Rapp-McCall, Jessica Nudo
Journal of Integrative Medicine    2021, 19 (2): 129-134.   DOI: 10.1016/j.joim.2020.11.004
Accepted: 13 October 2020
Online available: 28 November 2020

Abstract424)   HTML    PDF      
Objective
Patients who are involuntarily committed to a psychiatric facility often experience anxiety or increased anxiety in response to being placed in the institutional environment. The weighted blanket introduced a proactive treatment option. The purpose of this study was to evaluate patients' anxiety symptoms before and after weighted blanket, compared to a group that did not use a weighted blanket to control anxiety.

Methods
This study was conducted in an inpatient mental health facility from June 10, 2019, through November 7, 2019, with psychiatric patients who were not actively psychotic. Participants were offered the choice of weighted or unweighted blankets for a 20-minute intervention. The treatment group was comprised of individuals who had opted to use a 14-pound weighted blanket, 20-pound weighted blanket or 5-pound weighted lap pad. Participants in the comparison group had selected an un-weighted blanket. Before application of the blankets, pulse rate was measured using a pulse oximeter, and anxiety was measured using the Spielberger State-Trait Anxiety Inventory shortened form (STAI: Y-6). Both measures were taken again after the intervention. A two-way mixed analysis of variance (ANOVA) was run to examine the interaction effects between time (pre/post) and group (comparison/weighted blanket). Simple main effects were then further examined for the comparison/weighted blanket groups using a repeated measures ANOVA. Within the weighted blanket group, additional two-way mixed ANOVA was run to determine if gender or blanket weight made a statistically significant difference.

Results
There was a statistically significant difference (P < 0.05) among those who used weighted blankets (n = 61) and those who did not (n = 61) based on the pre/post data for both the STAI: Y-6 inventory and the patients’ pulse rates. The results of two-way ANOVA indicated a significant interaction effect between intervention time and group (P < 0.001). Repeated measures ANOVA indicated a change between pre/post for the weighted blanket group only, and showed significant reductions in both the STAI: Y-6 (P < 0.001) and pulse rates (P = 0.040). Within the weighted blanket group, additional two-way mixed ANOVA showed that neither gender nor blanket weight had significant difference for either the STAI: Y-6 or the pulse measures.

Conclusion
The use of weighted blankets is a safe and potentially effective way to help individuals in a psychiatric facility manage anxiety. This study found a statistically significant drop in anxiety for adults at an inpatient facility, as shown by the STAI: Y-6 scores and drop in pulse rates among patients using weighted blankets. This study suggests a possible alternative to medications, seclusion and physical restraints, which are not patient- centered or trauma-supported.
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Effects of Tanreqing Capsule on the negative conversion time of nucleic acid in patients with COVID-19: A retrospective cohort study
Xing Zhang, YanXue, Xuan Chen, Jia-min, Wu, Zi-jian Su, Meng Sun, Lu-jiong Liu, Yi-bao Zhang, Yi-le Zhang, Gui-hua Xu, Miao-yan Shi, Xiu-ming Song, Yun-fei Lu, Xiao-rong Chen, Wei Zhang, Qi Chen
Journal of Integrative Medicine    2021, 19 (1): 36-41.   DOI: 10.1016/j.joim.2020.10.002
Accepted: 07 August 2020
Online available: 09 October 2020

Abstract379)   HTML    PDF      
Objective
Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019 (COVID-19). Tanreqing Capsule (TRQC) was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center. This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19.

Methods
A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19; patients were treated with TRQC in one designated hospital. The treatment and control groups consisted of 25 and 57 cases, respectively. The treatment group was given TRQC orally three times a day, three pills each time, in addition to conventional Western medicine treatments which were also administered to the control group. The clinical efficacy indicators, such as the negative conversion time of pharyngeal swab nucleic acid, the negative conversion time of fecal nucleic acid, the duration of negative conversion of pharyngeal-fecal nucleic acid, and the improvement in the level of immune indicators such as T-cell subsets (CD3, CD4 and CD45) were monitored.

Results
COVID-19 patients in the treatment group, compared to the control group, had a shorter negative conversion time of fecal nucleic acid (4 vs. 9 days, P = 0.047) and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid (0 vs. 2 days, P = 0.042). The level of CD3+ T cells increased in the treatment group compared to the control group ([317.09 ± 274.39] vs. [175.02 ± 239.95] counts/μL, P = 0.030). No statistically significant differences were detected in the median improvement in levels of CD4+ T cells (173 vs. 107 counts/μL, P = 0.208) and CD45+ T cells (366 vs. 141 counts/μL, P = 0.117) between the treatment and control groups.

Conclusion
Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group, illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19. The underlying mechanism may be related to the improved levels of the immune indicator CD3+ T cells.
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Searching for the emotional roots of breast cancer: A cross-disciplinary analysis integrating psychology, Chinese medicine, and oncology biomarkers
Ofer Baranovitch, Meirav Wolff-Bar, Meora Feinmesser, Chen Sade-Zaltz, Ilan Tsarfaty, Victoria Neiman
Journal of Integrative Medicine    2022, 20 (1): 57-64.   DOI: 10.1016/j.joim.2021.11.005
Online available: 22 November 2021

Abstract359)   HTML    PDF      

Objective

We employed a multidisciplinary approach incorporating theoretical ideas, clinical experience, psychology, physiology, traditional Chinese medicine (CM), modern practice of CM, and oncology to explore the effect of patients’ repression of negative emotions and traumatic events on breast cancer (BC) pathogenesis.

Methods

BC female patients, older than 18 years of age, with available pathology reports who were treated at Rabin Medical Center were recruited. All participants completed questionnaires regarding medical history, behavioral tendencies, negative emotions, trauma, symptoms, and pathology (from a CM perspective). Data on tumor characteristics were collected from the pathology reports. The associations were examined using hierarchical binary logistic regressions. 

Results

A total of 155 BC patients were enrolled. The median age was 52 years, with a range of 26–79; 95% were mothers; 28% had estrogen receptor (ER)-negative BC, 52% had progesterone receptor (PR)-negative BC, 48% had human epidermal growth factor receptor 2-negative BC, and antigen Ki-67 ≥ 20% was reported for 52% of tumors. Statistically significant associations were found between the emotional markers (sense of motherhood failure, and lack of self-fulfillment), avoidance behavior, and physical symptoms that are related to emotional repression based on CM. Significant associations were also found between variables associated with physical symptoms of emotional repression, which involves the production and accumulation of non-substantial phlegm (i.e., “high-lipid Qi-like microscopic phlegm”), avoidance behavior which unconsciously uses “high-lipid Qi-like microscopic phlegm” in order to achieve emotional repression, and tumor parameters including tumor grade, PR status, and Ki-67. Patients with higher levels of “high-lipid Qi-like microscopic phlegm” were more likely to have tumors with worse prognosis (PR-negative, higher grade, and higher Ki-67). 

Conclusion

We demonstrated a relationship between emotional parameters, behavioral tendencies, CM parameters, and oncologic parameters in BC. Additional research is warranted to explore these associations and their relevance to clinical practice. 

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An overview of the anti-SARS-CoV-2 properties of Artemisia annua, its antiviral action, protein-associated mechanisms, and repurposing for COVID-19 treatment
Andréa D. Fuzimoto
Journal of Integrative Medicine    2021, 19 (5): 375-388.   DOI: 10.1016/j.joim.2021.07.003
Online available: 30 September 2021

Abstract317)   HTML    PDF      
Artemisia annua and its phytocompounds have a rich history in the research and treatment of malaria, rheumatoid arthritis, systemic lupus erythematosus, and other diseases. Currently, the World Health Organization recommends artemisinin-based combination therapy as the first-line treatment for multi-drug-resistant malaria. Due to the various research articles on the use of antimalarial drugs to treat coronaviruses, a question is raised: do A. annua and its compounds provide anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) properties. PubMed/MEDLINE, Scopus, and Google Scholar were searched for peer-reviewed articles that investigated the antiviral effects and mechanisms of A. annua and its phytochemicals against SARS-CoVs. Particularly, articles that studied the herb’s role in inhibiting the coronavirus-host proteins were favored. Nineteen studies were retrieved. From these, fourteen in silico molecular docking studies demonstrated potential inhibitory properties of artemisinins against coronavirus-host proteins, including 3CLPRO, S protein, N protein, E protein, cathepsin-L, helicase protein, nsp3, nsp10, nsp14, nsp15, and GRP78 receptor. Collectively, A. annua constituents may impede the SARS-CoV-2 attachment, membrane fusion, and internalization into the host cells, and hinder the viral replication and transcription process. This is the first comprehensive overview of the application of compounds from A. annua against SARS-CoV-2/coronavirus disease 2019 (COVID-19) describing all target proteins. A. annua’s biological properties, the signaling pathways implicated in the COVID-19, and the advantages and disadvantages for repurposing of A. annuacompounds are discussed. The combination of A. annua’s biological properties, action on different signaling pathways and target proteins, and a multi-drug combined-therapy approach may synergistically inhibit SARS-CoV-2 and assist in the COVID-19 treatment. Also, A. annua may modulate the host immune response to better fight the infection. 
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Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial
Jie Wu, Shu-wei Duan, Hong-tao Yang, Yue-yi Deng, Wei Li, Ya-ni He, Zhao-hui Ni, Yong-li Zhan, Shan Lin, Zhi-yong Guo, Jun Zhu, Jing-ai Fang, Xu-sheng Liu, Li-hua Wang, Rong Wang, Nian-song Wang, Xiao-hong Cheng, Li-qun He, Ping Luo, Shi-ren Sun s, Ji-feng Sun, Ai-ping Yin, Geng-ru Jiang, Hong-yu Chen, Wen-hu Liu, Hong-li Lin, Meng Liang, Lu Ma, Ming Chen, Li-qun Song, Jian Chen, Qing Zhu, Chang-ying Xing, Yun Li, Ji-ning Gao, Rong-shan Li, Ying Li, Hao Zhang, Ying Lu, Qiao-ling Zhou, Jun-zhou Fu, Qiang He, Guang-yan Cai, Xiang-mei Chen
Journal of Integrative Medicine    2021, 19 (2): 111-119.   DOI: 10.1016/j.joim.2021.01.009
Accepted: 16 December 2020
Online available: 30 January 2021

Abstract309)   HTML    PDF      
Background
Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.

Objective
This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.

Design, setting, participants and intervention
This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18–70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5–3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg.

Main outcome measures
The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.

Results
A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (= 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.

Conclusion
SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.

Trial registration number
NCT02063100 on ClinicalTrials.gov.
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Traditional chinese medicine targeting cancer stem cells as an alternative treatment for hepatocellular carcinoma
Kai-yue Tang, Shi-lin Du, Qian-lei Wang, Yi-fan Zhang, Hai-yan Song
Journal of Integrative Medicine    2020, 18 (3): 196-202.   DOI: 10.1016/j.joim.2020.02.002
Online available: 11 February 2020

Abstract280)   HTML    PDF      
Hepatocellular carcinoma (HCC) is a prevalent and highly malignant cancer throughout the world. Effective treatment of this disease is impeded by the high rate of metastasis, recurrence, and chemoresistance. Recent studies have revealed the close relationship between the malignant phenotype of HCC and cancer stem cells (CSCs). Therefore, CSC-targeted therapy is considered a promising strategy to eradicate HCC. Traditional Chinese medicine (TCM) can be effective in preventing recurrence and metastasis of some advanced HCC. A growing amount of literature has discovered that extracts or compounds derived from TCM exert an anti-CSC effect. This review introduces some formulas and chemical compounds derived from TCMs that have been reported to inhibit CSCs of HCC; these TCM-related drugs may help to provide an alternative approach to help manage cancers, especially for HCC which has a great potential of metastasis, recurrence, and chemoresistance.
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Caulerpa okamurae extract attenuates inflammatory interaction, regulates glucose metabolism and increases insulin sensitivity in 3T3-L1 adipocytes and RAW 264.7 macrophages
Bikash Manandhar, Hyun Jung Kim, Dong Young Rhyu
Journal of Integrative Medicine    2020, 18 (3): 253-264.   DOI: 10.1016/j.joim.2020.02.001
Accepted: 23 December 2019
Online available: 26 February 2020

Abstract241)   HTML    PDF      

Objective

To examine whether Caulerpa okamurae ethanolic extract (COE) could inhibit obesity-mediated inflammation, improve glucose metabolism and increases insulin sensitivity, using in vitro cell models of RAW 264.7 macrophages and 3T3-L1 adipocytes. 


Methods

We cocultured 3T3-L1 adipocytes in direct contact with lipopolysaccharide-stimulated RAW 264.7 macrophages and induced insulin resistance in 3T3-L1 adipocytes with tumor necrosis factor-α (TNF-α) in the presence or absence of 250 μg/mL of COE. We investigated various markers of inflammation, glucose regulation and insulin sensitivity in these models using Griess reagent to measure nitric oxide (NO) production, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose to measure glucose uptake, Western blot analysis to quantify protein expression and reverse transcriptase-polymerase chain reaction to evaluate mRNA expression.


Results

We found that COE (250 μg/mL) significantly inhibited the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages by downregulating NO production, nitric oxide synthase 2 expression and nuclear translocation of nuclear factor-κB. COE also showed similar anti-inflammatory activity in coculture, along with decreased TNF-α, interleukin-6 and monocyte chemoattractant protein mRNA expression. In addition, COE also improved glucose uptake in coculture by upregulating glucose transporter-4 (GLUT-4) and adiponectin and reducing serine phosphorylation of insulin receptor substrate-1 (IRS1). In the TNF-α-induced insulin resistance model of 3T3-L1 adipocytes, COE significantly improved both basal and insulin-stimulated glucose uptake, accompanied by phosphorylation of IRS1 at tyrosine 632, phospho-5' adenosine monophosphate-activated protein kinase α and glycogen synthase kinase-3β (Ser9) as well as upregulation of GLUT-4.


Conclusion

Together, these findings suggest that COE has potential to treat or prevent obesity-induced metabolic disorders.

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Removing barriers to healthcare through an intercultural healthcare system: Focus group evidence
Prince Peprah, Williams Agyemang-Duah, Abdul Wahid Arimiyaw, Anthony Kwame Morgan, Stephen Uwumbordo Nachibi
Journal of Integrative Medicine    2021, 19 (1): 29-35.   DOI: 10.1016/j.joim.2020.08.008
Accepted: 18 August 2020
Online available: 18 November 2020

Abstract229)   HTML    PDF      
Objective
Barriers to healthcare in Ghana are multifaceted. Many people, including patients and providers, face them at different levels. To address these barriers, there is a need to explore the role of an intercultural healthcare system. This paper explores and provides the first evidence on ways through which an intercultural healthcare system can reduce the sociocultural and economic barriers to healthcare in Ghana.

Methods
Focus group discussions with 35 participants comprising 17 healthcare users, 11 formal healthcare providers and 7 alternative healthcare providers were conducted to gather data. Thematic analyses were performed on the transcribed data and presented based on a posteriori inductive reduction approach.

Results
Findings reveal that an intercultural healthcare system in Ghana can help reduce barriers to healthcare, especially cultural, social and economic barriers, by fostering an enhanced relationship between culture and healthcare, promoting affordable healthcare and promoting effective communication between healthcare providers and users. Weak institutional support, lack of strong political will and commitment, lack of training to meet standards of practice, poor registration and regulatory measures, inadequate general acceptance by biomedical providers and a perceived negative perception of the intercultural healthcare policy inhibit implementation of an intercultural healthcare system in Ghana.

Conclusion
The support for intercultural healthcare system and the agreement on its perceived ability to reduce social, cultural and economic healthcare barriers for service users offer an opportunity for policy makers to demonstrate a stronger political will and improved political commitment for effective education and training, enforcement of regulatory measures, improved alternative medical literacy through the inclusion of intercultural healthcare medical school curricula across the country, and ensure increased community engagement.
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Analgesic and anti-inflammatory properties of hydroalcoholic extracts of Malva sylvestris, Carum carvi or Medicago sativa, and their combination in a rat model
Masoud Seddighfar, Sayid Mahdi Mirghazanfari, Masoumeh Dadpay
Journal of Integrative Medicine    2020, 18 (2): 181-188.   DOI: 10.1016/j.joim.2020.02.003
Online available: 07 February 2020

Abstract222)   HTML    PDF      
Objective
The aim of this study was to evaluate the analgesic and anti-inflammatory effects of the hydroalcoholic extracts of Malva sylvestris flowers or Carum carvi and Medicago sativa seeds, alone and in combination, which have been used in traditional Iranian medicine.

Methods
Male Wistar rats were divided into 6 treatment groups: distilled water, sodium salicylate (SS), M. sylvestris extract (600 mg/kg), C. carvi extract (600 mg/kg), M. sativa extract (300 mg/kg) and combined extract (including 300 mg/kg M. sylvestris and C. carvi extracts, and 150 mg/kg M. sativa extract). The formalin pain model was used to evaluate the antinociceptive effects of the treatments. For anti-inflammatory effect, acute (one hour after injection) and chronic (during a week after injection) paw inflammation was measured after subcutaneous injection of 2.5% formalin in the hindpaw. Finally, tissue samples from all groups were prepared for histopathological studies.

Results
The combined extract significantly inhibited the nociception in the acute phase of the formalin test (P < 0.001). In the chronic phase, all the extracts and SS had significant analgesic effect (P < 0.001). Analgesic activity of the combined extract was significantly stronger than SS (P < 0.01). In the acute inflammation model, M. sylvestris, C. carvi and the combined drug had significant inhibitory effects against paw edema (P < 0.05). All extracts, individually and in combination, significantly alleviated chronic paw inflammation (P < 0.01). The combined extract had much more anti-inflammatory activity than SS (P < 0.05). Histopathological results indicated improvement and reduction of inflammatory factors in the treatment groups.

Conclusion
M. sylvestris, C. carvi and M. sativa have analgesic and anti-inflammatory properties. Potentially, each of these extracts or a mixture of them might be a valuable alternative drug to control pain and inflammation.
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Extract of Naotaifang, a compound Chinese herbal medicine, protects neuron ferroptosis induced by acute cerebral ischemia in rats
Bin Lan, Jin-wen Ge, Shao-wu Cheng, Xi-long Zheng, Jun Liao, Chao He, Zheng-qing Rao, Guo-zuo Wang
Journal of Integrative Medicine    2020, 18 (4): 344-350.   DOI: 10.1016/j.joim.2020.01.008
Online available: 04 February 2020

Abstract218)   HTML    PDF      
Objective
Our previous research showed that Naotaifang (a compound traditional Chinese herbal medicine) extract (NTE) has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia. In this study, we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4 (GPX4) and iron metabolism.

Methods
We established an acute brain injury model of middle cerebral artery occlusion (MCAO) in rats, in which we could observe the accumulation of iron in neurons, as detected by Perl’s staining. Using assay kits, we measured expression levels of ferroptosis biomarkers, such as iron, glutathione (GSH), reactive oxygen species (ROS) and malonaldehyde (MDA); further the expression levels of transferrin receptor 1 (TFR1), divalent metal transporter 1 (DMT1), solute carrier family 7 member 11 (SLC7A11) and GPX4 were determined using immunohistochemical analysis, real-time quantitative polymerase chain reaction and Western blot assays.

Results
We found that treatment with NTE reduced the expression levels of TFR1 and DMT1, reduced ROS, MDA and iron accumulation and reduced neurobehavioral scores, relative to untreated MCAO rats. Treatment with NTE increased the expression levels of SLC7A11, GPX4 and GSH, and the number of Nissl bodies in the MCAO rats.

Conclusion
Taken together, our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7A11/GPX4 pathways.
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Perioperative transcutaneous electrical acupoint stimulation for improving postoperative gastrointestinal function: A randomized controlled trial
Wen-jing Li, Chao Gao, Li-xin An, Yu-wei Ji, Fu-shan Xue, Yi Du
Journal of Integrative Medicine    2021, 19 (3): 211-218.   DOI: 10.1016/j.joim.2021.01.005
Accepted: 16 November 2020
Online available: 13 January 2021

Abstract210)   HTML    PDF      

Background 

Postoperative gastrointestinal dysfunction (PGD) is one of the most common complications in patients undergoing major abdominal surgery. Acupuncture has been used widely in gastrointestinal diseases due to its effectiveness and minimally invasive nature.


Objective

This study evaluated the efficacy of using transcutaneous electrical acupoint stimulation (TEAS) during the surgery and postoperative recovery in patients with gastric and colorectal surgery for improving postoperative gastrointestinal function.


Design, setting, participants and interventions

A total of 280 patients undergoing abdominal surgery were stratified by type of surgery (i.e., gastric or colorectal surgery) and randomly allocated into the TEAS group (group T) or the sham group (group S). Patients in group T received TEAS at LI4, PC6, ST36 and ST37. Patients in group S received pseudo-TEAS at sham acupoints. The stimulation was given from 30 min before anesthesia until the end of surgery. The same treatment was performed at 9 am on the 1st, 2nd and 3rd days after surgery, until the recovery of flatus in patients.


Main outcome measures

The primary outcome was the time to the first bowel motion, as detected by auscultation. The secondary outcomes included the first flatus and ambulation time, changes of perioperative substance P (SP), incidence of PGD, postoperative pain, postoperative nausea and vomiting (PONV) and some economic indicators.


Results

The time to first bowel motion, first flatus and first ambulation in group T was much shorter than that in group S (P < 0.01). In patients undergoing colorectal surgery, the concentration of SP was lower in group T than in group S on the third day after the operation (P < 0.05). The average incidence of PGD in all patients was 25%, and the frequency of PGD was significantly lower in group T than in in group S (18.6% vs. 31.4%, respectively; P < 0.05). TEAS treatment (odds ratio = 0.498; 95% confidence interval: 0.232–0.786) and type of surgery were relevant factors for the development of PGD. Postoperative pain score and PONV occurrence were significantly lower in group T (P < 0.01). Postoperative hospitalization days and the resulting cost to patients were greatly reduced in the TEAS group (P < 0.01).


Conclusion

Perioperative TEAS was able to promote the recovery of postoperative gastrointestinal function, reduce the incidence of PGD and PONV. The concentration of SP was decreased by TEAS treatment, which indicates that the brain-gut axis may play a role in how TEAS regulates gastrointestinal function.


Trial registration

Chinese Clinical Trial Registry, ChiCTR1900023263.

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Anti-hemorrhoidal activity of Lian-Zhi-San, a traditional Chinese medicine, in an experimental hemorrhoidal model in rats
Hua Zhang, Xiang-yang Yao, Dan-feng Zhang, Qi-le Guo, Jun-jun Yang, Bao-guo Zhu, Dong-xiao Shen, Ke-feng Ruan, Yuan Wang, Jun-liang Peng
Journal of Integrative Medicine    2021, 19 (1): 42-49.   DOI: 10.1016/j.joim.2020.09.006
Online available: 22 January 2021

Abstract209)           

Objective

Hemorrhoidal disease (HD) is the most common proctological disease, with an estimated prevalence rate of 4.4%, and a peak in individuals between 45 and 65 years of age. This study was done to evaluate whether Lian-Zhi-San (LZS), a clinically used anti-hemorrhoidal ointment could alleviate the inflammatory injury, with its associated changes of inflammatory cytokines and morphology of anorectal tissues, in an experimental model of HD in rats.

Methods

HD was induced by croton oil preparation (COP) applied to the anorectal region. Rats were then treated with cotton swabs soaked in LZS ointment, water or white vaseline, twice a day for 7 d. At the end of the experiment, HD was evaluated by measuring hemorrhoidal and biochemical parameters along with histopathological observations. 

Results

In this study, COP induced a significant increase in the macroscopic severity score, anorectal coefficient and Evans blue extravasation, compared to normal rats. Additionally, it greatly enhanced the expression and secretion levels of some important inflammation-related cytokines along with marked histological damage, compared to normal rats. Rats treated with LZS ointment experienced significantly ameliorated Evans blue extravasation (P < 0.05), decreased macroscopic severity score (0.86 ± 0.14 vs. 1.65 ± 0.16) and the anorectal coefficient (P < 0.01); its use also attenuated tissue damage and inhibited the expression and secretion levels of inflammation-related cytokines (interleukin [IL]-1β, IL-6 and tumor necrosis factor-α).

Conclusion

This study validates a preliminary understanding of the use of LZS ointment to treat inflammatory factors and tissue damage in an experimental model of HD in rats.

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Chinese herbal medicines for prevention and treatment of colorectal cancer: from molecular mechanisms to potential clinical applications
Mu-yan Kong, Le-yan Li, Yan-mei Lou, Hong-yu Chi, Jin-jun Wu
Journal of Integrative Medicine    2020, 18 (5): 369-384.   DOI: 10.1016/j.joim.2020.07.005
Accepted: 29 June 2020
Online available: 30 July 2020

Abstract205)   HTML    PDF      
Worldwide, colorectal cancer (CRC) is one of the most common malignant tumors, leading to immense social and economic burdens. Currently, the main treatments for CRC include surgery, chemotherapy, radiotherapy and immunotherapy. Despite advances in the diagnosis and treatment of CRC, the prognosis for CRC patients remains poor. Furthermore, the occurrence of side effects and toxicities severely limits the clinical use of these therapies. Therefore, alternative medications with high efficacy but few side effects are needed. An increasing number of modern pharmacological studies and clinical trials have supported the effectiveness of Chinese herbal medicines (CHMs) for the prevention and treatment of CRC. CHMs may be able to effectively reduce the risk of CRC, alleviate the adverse reactions caused by chemotherapy, and prolong the survival time of patients with advanced CRC. Studies of molecular mechanisms have provided deeper insight into the roles of molecules from CHMs in treating CRC. This paper summarizes the current understanding of the use of CHMs for the prevention and treatment of CRC, the main molecular mechanisms involved in these processes, the role of CHMs in modulating chemotherapy-induced adverse reactions, and CHM’s potential role in epigenetic regulation of CRC. The current study provides beneficial information on the use of CHMs for the prevention and treatment of CRC in the clinic, and suggests novel directions for new drug discovery against CRC.
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Lavender and dodder combined herbal syrup versus citalopram in major depressive disorder with anxious distress: A double-blind randomized trial
Toktam Sadat Firoozeei, Majid Barekatain, Mehrdad Karimi, Arman Zargaran, Shahin Akhondzadeh, Hossein Rezaeizadeh
Journal of Integrative Medicine    2020, 18 (5): 409-415.   DOI: 10.1016/j.joim.2020.06.002
Accepted: 15 May 2020
Online available: 15 June 2020

Abstract198)   HTML    PDF      
Background
Major depressive disorder (MDD) accompanied by anxious distress is a chronic and disabling disorder. Its conventional drug therapies often have low patient compliance due to drug-related side effects. In Persian medicine, lavender-dodder syrup is one formula often recommended for such disorders.

Objective
This study compares the effects of lavender-dodder syrup to the standard drug, citalopram, for treating MDD with anxious distress.

Design, setting, participants and intervention
This six-week, double-blind, randomized, clinical trial was carried out in a psychiatric outpatient clinic. During the six-week intervention period, patients in citalopram group received citalopram tablets 20 mg/d plus 5 mL placebo syrup every 12 h; patients in group B received placebo tablets once daily plus 5 mL of lavender-dodder herbal syrup every 12 h.

Main outcome measures
Primary outcome measures, depression and anxiety, were evaluated using the Hamilton Depression/Anxiety Rating Scales, and were scored at the beginning of the study and at weeks three and six. Secondary outcome measures including response to treatment and remission rates were also compared between the two groups.

Results
Fifty-six participants with MDD and anxious distress were randomly assigned to two groups. Mean depression scores significantly decreased in citalopram and herbal groups at weeks three and six (time effect: P < 0.001), although the observed changes were not significantly different between the groups (intervention effect: P = 0.61). Mean anxiety scores were not significantly different between the two groups at week three (P = 0.75). However, at the end of week six, the observed decrease was significantly higher in the herbal syrup group than the citalopram group (intervention effect: P = 0.007).

Conclusion
The herbal syrup is an effective and tolerable supplement for treating MDD with anxious distress.
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Effects of a Plantago ovata-based herbal compound in prevention and treatment of oral mucositis in patients with breast cancer receiving chemotherapy: A double-blind, randomized, controlled crossover trial
Fatemeh Sadat Hasheminas, Seyed Mehdi Hashemi, Azizallah Dehghan, Fariba Sharififar, Mohammad Setayesh, Pegah Sasanpour, Mojtaba Tasbandi, Mahboobeh Raeiszadeh
Journal of Integrative Medicine    2020, 18 (3): 214-221.   DOI: 10.1016/j.joim.2020.02.008
Accepted: 18 January 2020
Online available: 05 March 2020

Abstract198)   HTML    PDF      
Background
Oral mucositis (OM) is one of the most common complications of mucotoxic cancer therapy. Mucositis induces clinically significant pain, increases the risk of infections and affects the patients’ quality of life.

Objective
This study investigated the effects of an herbal preparation from Plantago ovata hydrocolloid in the prevention and treatment of OM, in breast cancer patients undergoing chemotherapy with a regimen including adriamycin.

Design, setting, participants, and interventions
This research was a double-blind, randomized, controlled crossover trial. The herbal compound consisted of a mixture of 500 mg of P. ovate husk in 30 mL water plus three drops of vinegar per dose, which was used as a mouthwash. Phytochemical and physicochemical tests of the compound were also performed. Twenty-eight patients who developed mucositis during the chemotherapy screening cycle were randomized to the herbal compound (n = 14) and placebo (n = 14) groups. They received herbal compound or placebo three times per day during their next chemotherapy cycle (cycle 1 of treatment). Patients were crossed over during cycle 2 of treatment and received the alternative therapy. An oral care protocol was prescribed to all patients in cycles 1 and 2 of the treatment.

Main outcome measures
The patients were visited at baseline, the end of the first and second weeks of the screening cycle, and the end of the first and second weeks of each of two treatment cycles. The degree of mucositis was used as the main treatment outcome. Other indexes, such as the severity of pain, xerostomia grade and the quality of life were also measured.

Results
Compared with the placebo, the herbal compound significantly reduced the degree of mucositis, the severity of pain and the xerostomia grade; it also improved the patients’ quality of life (P < 0.05). Comparison between the screening cycle and placebo treatment group showed that the oral care protocol had a significant effect in the reduction of OM (P < 0.05).

Conclusion
The oral care protocol and the herbal compound based on P. ovata are effective ways for preventing and treating OM in patients undergoing mucotoxic cancer therapy.

Trial registration: Iranian registry of clinical trials IRCT20180923041093N1.
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Phenolic constituents and anticancer properties of Morus alba (white mulberry) leaves
Eric Wei Chiang Chan, Siu Kuin Wong, Joseph Tangah, Tomomi Inoue, Hung Tuck Chan
Journal of Integrative Medicine    2020, 18 (3): 189-195.   DOI: 10.1016/j.joim.2020.02.006
Accepted: 14 January 2020
Online available: 20 February 2020

Abstract194)   HTML    PDF      
Flavonoids are by far the most dominant class of phenolic compounds isolated from Morus alba leaves (MAL). Other classes of compounds are benzofurans, phenolic acids, alkaloids, coumarins, chalcones and stilbenes. Major flavonoids are kuwanons, moracinflavans, moragrols and morkotins. Other major compounds include moracins (benzofurans), caffeoylquinic acids (phenolic acids) and morachalcones (chalcones). Research on the anticancer properties of MAL entailed in vitro and in vivo cytotoxicity of extracts or isolated compounds. Flavonoids, benzofurans, chalcones and alkaloids are classes of compounds from MAL that have been found to be cytotoxic towards human cancer cell lines. Further studies on the phytochemistry and anticancer of MAL are suggested. Sources of information were PubMed, PubMed Central, ScienceDirect, Google, Google Scholar, J-Stage, PubChem and China National Knowledge Infrastructure.
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Alleviative effects of Cannabis flower on migraine and headache
Sarah S. Stith, Jegason P. Diviant, Franco Brockelman, Keenan Keeling, Branden Hall, Storri Lucern, Jacob M. Vigil
Journal of Integrative Medicine    2020, 18 (5): 416-424.   DOI: 10.1016/j.joim.2020.07.004
Online available: 29 July 2020

Abstract192)   HTML    PDF      
Objective: Few studies to date have measured the real-time effects of consumption of common and commercially available Cannabisproducts for the treatment of headache and migraine under naturalistic conditions. This study examines, for the first time, the effectiveness of using dried Cannabis flower, the most widely used type of Cannabis product in the United States, in actual time for treatment of headache- and migraine-related pain and the associations between different product characteristics and changes in symptom intensity following Cannabis use.
Methods: Between 06/10/2016 and 02/12/2019, 699 people used the Releaf Application to record real-time details of their Cannabisuse, including product characteristics and symptom intensity levels prior to and following self-administration; data included 1910 session-level attempts to treat headache- (1328 sessions) or migraine-related pain (582 sessions). Changes in headache- or migraine-related pain intensity were measured on a 0-10 scale prior to, and immediately, following Cannabis consumption.
Results: Ninety-four percent of users experienced symptom relief within a two-hour observation window. The average symptom intensity reduction was 3.3 points on a 0-10 scale (standard deviation = 2.28, Cohen’s d = 1.58), with males experiencing greater relief than females (P < 0.001) and a trend that younger users (< 35 years) experience greater relief than older users (P = 0.08). Mixed effects regression models showed that, among the known (i.e., labeled) product characteristics, tetrahydrocannabinol levels 10% and higher are the strongest independent predictors of symptom relief, and this effect is particularly prominent in headache rather than migraine sufferers (P < 0.05), females (P < 0.05) and younger users (P < 0.001). Females and younger users also appear to gain greater symptom relief from flower labeled as “C. indica” rather than “C. sativa” or other hybrid strains. 
Conclusion: These results suggest that whole dried Cannabis flower may be an effective medication for treatment of migraine- and headache-related pain, but the effectiveness differs according to characteristics of the Cannabis plant, the combustion methods, and the age and gender of the patient. 
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Fuzheng Huayu recipe, a traditional Chinese compound herbal medicine, attenuates renal interstitial fibrosis via targeting the miR-21/PTEN/AKT axis
Qing-lan Wang, Yan-yan Tao, Hong-dong Xie, Cheng-hai Liu, Ping Liu
Journal of Integrative Medicine    2020, 18 (6): 505-513.   DOI: 10.1016/j.joim.2020.08.006
Accepted: 01 July 2020
Online available: 28 August 2020

Abstract191)   HTML    PDF      
Objective

MicroRNAs (miRNAs) may be viable targets for treating renal interstitial fibrosis (RIF). Fuzheng Huayu recipe (FZHY), a traditional Chinese compound herbal medicine, is often used in China to treat fibrosis. This study sought to assess the mechanisms through which FZHY influences miRNAs to treat RIF.

Methods

RIF was induced in rats by mercury chloride and treated with FZHY. Hydroxyproline content, Masson’s staining and type I collagen expression were used to evaluate renal collagen deposition. Renal miRNA profiles were evaluated using a miRNA microarray. Those miRNAs that were differentially expressed following FZHY treatment were identified and subjected to bioinformatic analyses. The miR-21 target gene phosphatase and tensin homolog (PTEN) expression and AKT phosphorylation in kidney tissues were assessed via Western blotting. In addition, HK-2 human proximal tubule epithelial cells were treated using angiotensin II (Ang-II) to induce epithelial-to-mesenchymal transition (EMT), followed by FZHY exposure. miR-21 and PTEN expressions were evaluated via quantitative reverse transcription-polymerase chain reaction (qRT-PCR), while E-cadherin and α-smooth muscle actin (α-SMA) expressions were assessed by immunofluorescent staining and qRT-PCR. Western blotting was used to assess PTEN and AKT phosphorylation.

Results

FZHY significantly decreased kidney collagen deposition, hydroxyproline content and type I collagen level. The miRNA microarray identified 20 miRNAs that were differentially expressed in response to FZHY treatment. Subsequent bioinformatic analyses found that miR-21 was the key fibrosis-related miRNA regulated by FZHY. FZHY also decreased PTEN expression and AKT phosphorylation in fibrotic kidneys. Results from in vitro tests also suggested that FZHY promoted E-cadherin upregulation and inhibited α-SMA expression in Ang-II-treated HK-2 cells, effectively reversing Ang-II-mediated EMT. We also determined that FZHY reduced miR-21 expression, increased PTEN expression and decreased AKT phosphorylation in these cells.

Conclusion

miR-21 is the key fibrosis-related miRNA regulated by FZHY. The ability of FZHY to modulate miR-21/PTEN/AKT signaling may be a viable approach for treating RIF.
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Modified Zhibai Dihuang pill, a traditional Chinese medicine formula, on steroid withdrawal in systemic lupus erythematosus: A systematic review and meta-analysis
Liang Dai, Ka Kei Chan, Jian-chun Mao, Yu Tian, Jun-hua Gu, Jun Zhou, Linda L.D. Zhong
Journal of Integrative Medicine    2020, 18 (6): 478-491.   DOI: 10.1016/j.joim.2020.08.007
Accepted: 04 August 2020
Online available: 26 August 2020

Abstract189)   HTML    PDF      
Background
Zhibai Dihuang pill (ZBDH), a Chinese herbal formula, has been widely used as an adjunctive therapy to help reduce a patient's steroid dose while maintaining low disease activity in systemic lupus erythematosus (SLE).

Objective
This systematic review evaluates the therapeutic effect of modified ZBDH in reducing steroid use in patients with SLE.

Search strategy
A systematic literature search was carried out using seven databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese VIP Information and Wanfang Database, from their inception to June 1st, 2019. The search terms included “systemic lupus erythematosus,” “Chinese medicine” and “clinical trial,” and their synonyms. Subject headings matching the above terms were also used.

Inclusion criteria
This meta-analysis included randomized controlled trials that evaluated the reduction of steroid dose in patients with SLE. Traditional Chinese medicine (TCM) formulas in experimental group should be prescribed based on ZBDH and used as adjunctive therapy and the comparator should contain steroids.

Data extraction and analysis
Two authors independently conducted database searches, study selection, data extraction and quality assessment. The extracted information contained study design, sample size, recruitment mode, diagnostic criteria, inclusion and exclusion criteria, participant characteristics, TCM patterns, TCM formulas and treatment outcomes. The primary outcome was the change of steroid dose. Secondary outcomes included SLE Disease Activity Index (SLEDAI), biomarkers of disease activity and clinical response rate. STATA 15.0 was used to analyze the pooled effects reported as weighted mean difference (WMD) or odds ratio, with a 95% confidence interval (CI).

Results
In total, 20 trials involving 1470 SLE patients were included. The pooled result showed that modified ZBDH taken in combination with standard care led to a larger reduction in steroid dose, compared to standard care alone (WMD: 3.79; 95% CI: 2.58–5.01; P < 0.001). Favorable outcomes were also seen in secondary outcome criteria, such as SLEDAI and complement 3. The modified ZBDH treatments were well tolerated without increasing adverse effects.

Conclusion
The systematic review provided preliminary evidence supporting the use of ZBDH as a co-therapy to aid steroid dose reduction in patients with SLE. However, more rigorous studies should be conducted to validate these findings, and explore the mechanisms of ZBDH’s relevant bioactive constituents.
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Evaluation of anticancer effects of a pharmaceutically viable extract of a traditional polyherbal mixture against non-small-cell lung cancer cells
Varuni Colamba Pathiranage, Ira Thabrew, Sameera R. Samarakoon, Kamani H. Tennekoon, Umapriyatharshini Rajagopalan, Meran K. Ediriweera
Journal of Integrative Medicine    2020, 18 (3): 242-252.  
Accepted: 20 August 2019
Online available: 26 February 2020

Abstract184)   HTML    PDF      
Objective:
The present work tested organic solvents to prepare an extract with anticancer properties from a polyherbal mixture containing Nigella sativa (seeds), Hemidesmus indicus (roots) and Smilax glabra (rhizomes). We evaluate anticancer effects in non-small-cell lung cancer cells (NCI-H292), and discuss optimization for pharmaceutical use in the context of efficacy, yield and toxicity.
Methods:
Using different organic solvents, six extracts were prepared from the polyherbal mixture. Based on the cytotoxic effects of these extracts on NCI-H292 cells and normal lung cells (MRC-5), as evaluated by the sulphorhodamine B assay, the total ethyl acetate (T-EA) extract was selected for further analysis. The possible anticancer mechanisms were assessed by evaluating the extract’s effects on apoptosis (through fluorescent microscopic analysis, DNA fragmentation analysis, caspase 3/7 assay and analysis of expression levels of apoptosis-related genes p53, Bax, survivin, Hsp70 and Hsp90), colony formation and antioxidant activity.
Results:
The extract had cytotoxic effects against NCI-H292 cells in a time- and dose-dependent manner. Significant antioxidant activity and inhibition of colony formation were also observed. The expression level of caspase 3/7 significantly (P ? 0.001) increased in NCI-H292 cells treated with 50 μg/mL of the extract. The same dosage led to a significant increase in expression levels of Bax and p53 (P ? 0.05 and P ? 0.01 respectively), accompanied by a significant decrease (P ? 0.0001) in survivin, Hsp 70 and Hsp 90.
Conclusion:
T-EA extract of the above polyherbal mixture has cytotoxicity against NCI-H292 cells via induction of apoptosis, antioxidant effects and inhibition of colony formation
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Integration of network and experimental pharmacology to decipher the antidiabetic action of Duranta repens L.
Pukar Khanal, Basanagouda M. Patil
Journal of Integrative Medicine    2021, 19 (1): 66-77.   DOI: 10.1016/j.joim.2020.10.003
Accepted: 28 August 2020
Online available: 07 October 2020

Abstract176)   HTML    PDF      
Objective
Duranta repens is reported to contain a wide array of secondary metabolites, including α-amylase and α-glucosidase inhibitors, and it has potent antioxidant activity. The present study evaluated the network pharmacology of D. repens (whole plant) with targets related to diabetes mellitus and assessed its outcome by evaluating the effects of the hydroalcoholic extract of D. repens in streptozotocin-nicotinamide-induced diabetes mellitus.

Methods
Phytoconstituents of D. repens were retrieved from an open-source database and published literature, and their targets were predicted for diabetes mellitus using BindingDB and the therapeutic target database. Protein-protein interaction was predicted using STRING, and pathways involved in diabetes mellitus were identified using the Kyoto Encyclopedia of Genes and Genomes pathway browser. Druglikeness, ADMET profile (absorption, distribution, metabolism, excretion and toxicity) and cytotoxicity of compounds modulating proteins involved in diabetes were predicted using MolSoft, admetSAR2.0 and CLC-Pred, respectively. The interaction network among phytoconstituents, proteins and pathways was constructed using Cytoscape, and the docking study was performed using autodock4.0. The hydroalcoholic extract of D. repens was evaluated using streptozotocin-nicotinamide-induced diabetes mellitus animal model for 28 d, followed by an oral glucose tolerance test. At the end of the study, biochemical parameters like glycogen content, hepatic enzymes, antioxidant biomarkers and lipid profiles were quantified. Further, the liver and pancreas were collected for a histopathology study.

Results
Thirty-six different secondary metabolites from D. repens were identified to regulate thirty-one targets involved in diabetes mellitus, in which protein-tyrosine phosphatase 1B (PTP1B) was primarily targeted. Enrichment analysis of modulated proteins identified 12 different pathways in diabetic pathogenesis in which the phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway was chiefly regulated. The docking study found that durantanin I possessed the highest binding affinity (–8.9 kcal/mol) with PTP1B. Similarly, ADMET profiling showed that the majority of bioactive constituents from D. repens had higher human intestinal absorptivity and minimal cytotoxicity to normal cell lines, than tumor cell lines. Further, an in vivo animal study reflected the efficacy of the hydroalcoholic extract of D. repens to lower the elevated blood glucose level by stimulating insulin secretion, maintaining pancreatic β cell mass, regulating glycolysis/gluconeogenesis and upregulating the glucose uptake in skeletal muscles.

Conclusion
The present study reflected the probable network interaction of bioactive constituents from D. repens, their targets and modulated pathways, which identified the prime regulation of the PI3K-Akt signaling pathway and PTP1B protein. Modulation of PTP1B protein and PI3K-Akt signaling pathway could contribute to enhancing glucose uptake, insulin production and glycolysis and decreasing gluconeogenesis in diabetes, which was evaluated via the experimental study.

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Effects of co-administration of Ganoderma terpenoid extract with chloroquine on inflammatory markers and antioxidant status in Plasmodium berghei-infected mice
Olarewaju M. Oluba, Oghenerobor B. Akpor, Feyikemi D. Adebiyi, Sunday J. Josiah, Olayinka O. Alabi, Ayoola O. Shoyombo, Augustine O. Olusola
Journal of Integrative Medicine    2020, 18 (6): 522-529.   DOI: 10.1016/j.joim.2020.08.002
Accepted: 20 July 2020
Online available: 21 August 2020

Abstract173)   HTML    PDF      
Objective

To understand the protective effects of Ganoderma terpenoid extract (GTE) against Plasmodium berghei-malarial infection in mice, the present study was carried out to evaluate the effects of GTE in combination with chloroquine disulphate (CQ) on erythrocyte-selected inflammatory markers and antioxidant defense status in P. berghei-infected mice. 

Methods

P. berghei-infected mice were divided into six groups: infected control (IC) group, administered 1 mL Tween 20; GTE100 and GTE250 groups, administered 100 and 250 mg/kg GTE, respectively; GT100 + CQ and GT250 + CQ groups, co-administered 100 and 250 mg/kg GTE plus 30 mg/kg CQ, respectively; and CQ group, administered 30 mg/kg CQ. A separate group of non-infected mice were given 1 mL Tween 20, and served as a normal control group (NC). Extract and drug were dissolved in Tween 20 and administered orally once daily for 12 consecutive days. At the end of the treatment period, mice were anesthetized with chloroform and sacrificed by cervical dislocation. Plasma was prepared from blood obtained from each mouse. Parameters evaluated at the end of the treatment period include parasitemia, red blood cell count, hematocrit, malondialdehyde (MDA), glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10). 

Results

Infected mice treated with a combination of GTE and CQ (GT100 + CQ and GT250 + CQ groups) showed significantly reduced parasitemia levels (P < 0.05) compared to those administered GTE alone as well as IC. Significant improvement in body weight (P < 0.05) was also observed in infected mice treated with a combination of GTE and CQ (GT100 + CQ and GT250 + CQ groups), compared to mice receiving GTE alone (GTE100 and GTE250 groups). Plasma MDA and TNF-α concentrations were significantly lowered, and IL-10 concentration was significantly increased in GT100 + CQ and GT250 + CQ groups, relative to the IC group (P < 0.05). GSH concentration and SOD, CAT and GPx activities were significantly higher in GT100 + CQ and GT250 + CQ groups compared to the GTE100, GTE250, IC and NC groups (P < 0.05). 

Conclusion

Data generated in this study showed that GTE enhanced the anti-plasmodial action of CQ in mice through its anti-inflammatory and antioxidant activities.

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Traditional Chinese medicine in the treatment of idiopathic pulmonary fibrosis based on syndrome differentiation: Study protocol of exploratory trial
Xue-qing Yu, Shu-guang Yang, Yang Xie, Jian-sheng Li
Journal of Integrative Medicine    2020, 18 (2): 163-168.   DOI: 10.1016/j.joim.2019.12.005
Online available: 27 December 2019

Abstract170)   HTML    PDF      

Background

Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and is often a kind of heavy financial burden to patients. Currently, few treatments are available for IPF. Clinical practice of traditional Chinese medicine (TCM), using a syndrome differentiation approach, offers some treatment success in IPF. However, there is insufficient evidence-based study of the role of TCM in IPF management to make strong conclusions. This study evaluates the efficacy and safety of TCM, using a syndrome differentiation approach, in the treatment of IPF. 


Methods and design

A multicenter, exploratory, randomized, double-blind and placebo-controlled trial is planned. A total of 80 patients will be enrolled in the study, which will include 26 weeks of treatment. Participants will be randomly assigned into TCM group or control group in a 1:1 ratio. The TCM group are designed to be given TCM granules based on syndrome differentiation. Formulae include Bu-Fei Yi-Qi granule for lung qi deficiency, Bu-Fei Yi-Shen granule for lung-kidney qi deficiency and Yang-Yin Qing-Re granule for yin deficiency and inter heat. The control group will be given a corresponding TCM granule placebo. The efficacy and safety of interventions will be evaluated by the outcome variables, including frequencies of acute exacerbations, pulmonary function, clinical symptoms, dyspnea, health-related quality of life (HRQoL), 6-minute walk distance and safety indicators. 


Discussion

It is hypothesized that TCM will decrease the frequency of adverse events, improve pulmonary function and HRQoL, based on our clinical experience. This trial is the first study of TCM treatment in IPF that is based on syndrome differentiation and will evaluate efficacy and safety of TCM in IPF. 


Trial registration

This study was registered on www.Chictr.org.cn: ChiCTR-IIR-17013532. Register date: November 24, 2017.

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Evaluation of antioxidant capacity and reproductive toxicity of aqueous extract of Thai Mucuna pruriens seeds
Sitthichai Iamsaard, Supatcharee Arun, Jaturon Burawat, Supataechasit Yannasithinon, Saranya Tongpan, Sudtida Bunsueb, Natthapol Lapyuneyong, Pannawat Choowong-in, Nareelak Tangsrisakda, Chadaporn Chaimontri, Wannisa Sukhorum
Journal of Integrative Medicine    2020, 18 (3): 265-273.   DOI: 10.1016/j.joim.2020.03.003
Accepted: 04 February 2020
Online available: 23 March 2020

Abstract163)   HTML    PDF      
Objective
In traditional medicine, the seeds of Thai Mucuna pruriens (T-MP) are used to treat male dysuria and are believed to enhance fertility. However, information pertaining to the toxicity of T-MP and its interaction with other properties is limited. This study was thus conducted to evaluate the antioxidant capacity and subacute toxicity of T-MP in the reproductive system.

Methods
Total phenolic content and antioxidant capacity of T-MP seed extract were determined using total phenolic content, 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays. Male and female adult rats were treated orally with T-MP at a dosage of 150 or 300 mg/kg body weight for 14 consecutive days. Sex hormones and functional parameters in the liver and kidney were evaluated. Histopathology of all tissue was conducted using Masson’s trichrome staining. Sperm parameters, including concentration, morphology, acrosome reaction status and DNA damage, were also examined. Expression of tyrosine phosphorylated protein (TyrPho), androgen receptor and A-kinase-anchoring protein 4 (AKAP4) were investigated using the Western blot technique.

Results
T-MP seed extract contained phenolic compounds and exhibited high antioxidant capacity with no toxicity at the tested doses. It did not affect liver or kidney function parameters in the male rats, but increased estradiol, aspartate aminotransferase and alanine aminotransferase levels in the females. Additionally, it decreased serum progesterone and alkaline phosphatase levels in female rats. Serum and intratesticular testosterone levels were significantly lower in male rats that received a high dosage of T-MP. Histopathological changes were not observed in any tissue treated with T-MP. T-MP also significantly increased sperm concentration (but did not affect sperm parameters), and enhanced testicular TyrPho protein and androgen receptor and expression of AKAP4 in sperms.

Conclusion
T-MP seed extract exhibited antioxidant capacity and was not harmful to reproductive tissues. It also had a phytoestrogenic effect on females and increased the expression of testicular and sperm markers of male fertility.
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Traditional Chinese medicine is a useful and promising alternative strategy for treatment of Sjogren's syndrome: A review
Shu-jun Wei, Qing-man He, Qing Zhang, Kang-hua Fu, Ruo-lan Li, Wei Peng, Yong-xiang Gao
Journal of Integrative Medicine    2021, 19 (3): 191-202.   DOI: 10.1016/j.joim.2021.01.008
Accepted: 11 November 2020
Online available: 14 January 2021

Abstract162)   HTML    PDF      
Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease involving exocrine glands. Current studies have found that the occurrence of the disease is closely related to genetic, environmental and neuroendocrine factors, as well as abnormal activation of T and B lymphocytes. The etiology and pathogenesis of pSS is complex, and there is a lack of specific targeted drugs. Traditional Chinese medicines (TCMs) have been comprehensively investigated for their treatment effects on pSS. Through a systematic review of the literature, we summarized the TCMs used to treat pSS, and find that there are four major ways that TCMs are used, including upregulation of aquaporin proteins, suppression of cell apoptosis, suppression of the abnormal activation of B lymphocytes and suppression of the abnormal activation of T lymphocytes (balancing T helper type [Th]1/Th2 & Th17/Treg and suppressing follicular helper T [Tfh] cells). However, there are not enough data about the active constituents, quality control, pharmacokinetics, toxicity and modern preparations of these TCMs; therefore, more investigations are needed. This paper highlights the importance of TCMs for treating pSS and provides guidance for future investigations.
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Effects of traditional Chinese exercises and general aerobic exercises on older adults with sleep disorders: A systematic review and meta-analysis
Yang-hao-tian Wu, Wen-bo He, Yin-yan Gao, Xue-mei Han
Journal of Integrative Medicine    2021, 19 (6): 493-502.   DOI: 10.1016/j.joim.2021.09.007
Online available: 09 October 2021

Abstract159)           

Background

Sleep disorders are common in older adults and have a negative influence on their physical and mental health. General aerobic exercises (GAEs) have long been used in the treatment of sleep disorders as a non-pharmacological measure. However, there is no consensus on the efficacy of traditional Chinese exercises (TCEs) for treating sleep disorders in older adults and the difference between TCEs and GAEs.

Objective

This study assessed the effects of TCEs and GAEs on the sleep quality of older adults and the differences between these two interventions.

Search strategy

PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, China Science Journal Database and Wanfang Data were searched from their inception to August 2020. 

Inclusion criteria

Randomized controlled trials (RCTs) that evaluated the effects of TCEs and GAEs on older adults with sleep disorders were included. 

Data extraction and analysis

Data were extracted by two researchers working independently. The risk bias of included studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 and the quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. The Pittsburgh Sleep Quality Index (PSQI) was used to estimate sleep quality. Meta-analyses were performed to assess the total PSQI score of the exercise intervention as the primary outcome, and the scores of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction were assessed as secondary outcomes. Subgroup, sensitivity, and meta-regression analyses were conducted to assess the contribution of covariables to heterogeneity.

Results

A total of 22 RCTs (including 1747 participants) were included in the meta-analysis. The results indicated that TCEs (weighted mean difference [WMD] = –2.14, 95% confidence interval [CI] [–2.82, –1.46], P < 0.001; heterogeneity: P < 0.001, I2 = 82%; 15 studies, n = 1063) and GAEs (WMD = –2.88, 95% CI [–5.22, –0.55], P  < 0.001; heterogeneity: P  < 0.001, I2 = 98%; 5 studies, n = 500) significantly improved total sleep quality, having favorable effects on subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction. Subgroup analysis showed that TCEs demonstrated superiority after 12 weeks (WMD = –2.77, 95% CI [–4.26, –1.28], P  < 0.001; heterogeneity: P  < 0.001, I2 = 85%; 5 studies, n = 420) and Qigong had a greater intervention effect for improving the sleep quality of older adults than Tai Chi (WMD = –3.37, 95% CI [–4.38, –2.35], P  < 0.001; heterogeneity: P  = 0.04, I2 = 63%; 4 studies, n = 321). Meta-regression revealed that the year of publication, sample size, mean age of participants, and percentage of females in the primary studies did not account for the overall heterogeneity.

Conclusion

Current evidence shows that both TCEs and GAEs, as complementary and non-pharmacological approaches, help to improve the sleep quality in older adults with potentially clinical implications; however, there was not enough evidence to conclude the difference between them. More rigorous and high-quality RCTs are needed to arrive at reliable conclusions.

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Knowledge about, attitude and acceptance towards, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China: A cross-sectional survey
Jing Hong, Xiao-wan Xu, Jing Yang, Jing Zheng, Shu-mei Dai, Ju Zhou, Qing-mei Zhang, Yi Ruan, Chang-quan Ling
Journal of Integrative Medicine    2022, 20 (1): 34-44.   DOI: 10.1016/j.joim.2021.10.004
Accepted: 11 October 2021
Online available: 26 October 2021

Abstract154)   HTML    PDF      
Objective
The coronavirus disease 2019 (COVID-19) pandemic has had a serious impact on health all over the world. Cancer patient, whose immunity is often compromised, faces a huge challenge. Currently, some COVID-19 vaccines are being developed and applied on general population; however, whether cancer patients should take COVID-19 vaccine remains unknown. Our study aimed to explore the knowledge, attitude, acceptance, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China.

Methods
A cross-sectional study was conducted in Eastern China from June 17th to September 3rd, 2021. Patients were selected using a convenience sampling method. A self-report questionnaire was developed to assess knowledge about the COVID-19 vaccine, attitude towards the vaccine and acceptance of the vaccine; following a review of similar studies previously published in the scientific literature, multivariate logistic regression analysis was used to determine the predictors associated with COVID-19 vaccine acceptance.

Results
A total of 2158 cancer patients were enrolled in this study. The rate of vaccine hesitancy was 24.05% (519/2158); further, among the participants of vaccine acceptance, 767 had taken COVID-19 vaccine (35.54%), and 872 were willing to get vaccinated (40.01%). A total of 24 variables including demographic characteristics, clinical status of cancer, impact of COVID-19 pandemic on study participants, patients’ knowledge about the COVID-19 vaccine, and attitude towards the vaccine, had significant differences between the “vaccine hesitancy” population and “vaccine acceptance” population. Multivariate logistic regression analysis indicated that parameters including alcohol consumption (odds ratio [OR] = 1.849; 95% confidence interval [CI]: 1.375–2.488; P-Ref < 0.001 vs non-drinkers), income impacted by COVID-19 pandemic (OR = 1.930, 2.037 and 2.688 for mild, moderate, and severe impact, respectively; all P-Ref < 0.01 vs no impact), knowledge of how the vaccine was developed (OR = 1.616; 95% CI: 1.126–2.318; P-Ref = 0.009 vs unknown), believing in the safety of the vaccine (OR = 1.502; 95% CI: 1.024–2.203; P-Ref = 0.038 vs denying the safety of vaccine), willingness to pay for the vaccine (OR = 3.042; 95% CI: 2.376–3.894; P-Ref < 0.001 vs unwilling), and willingness to recommend families and friends to get vaccinated (OR = 2.744; 95% CI: 1.759–4.280; P-Ref < 0.001 vs do not recommend) were contributors to vaccine acceptance. While such as being retired (OR = 0.586; 95% CI: 0.438–0.784; P-Ref < 0.001 vs unemployed), undergoing multiple therapies of cancer (OR = 0.408; 95% CI: 0.221–0.753; P-Ref = 0.004 vs no ongoing treatment), and worrying that the vaccine might deteriorate the prognosis of cancer (OR = 0.393; 95% CI: 0.307–0.504; P-Ref < 0.001 vs might not) were contributors to vaccine hesitancy.

Conclusion
This study provided preliminary estimates of the rates of vaccine acceptance and vaccine hesitancy among cancer patients in Eastern China. The intention to receive the COVID-19 vaccine was impacted by factors such as patient occupation, alcohol consumption, and some parts of knowledge about and attitude towards COVID-19 vaccine. It is recommended to develop individualized vaccination plans that meet the healthcare needs of cancer patients.
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Are the release characteristics of Erzhi pills in line with traditional Chinese medicine theory? A quantitative study
Jie-yu Zuo, Chulhun Park, Michael Doschak, Raimar Löbenberg
Journal of Integrative Medicine    2021, 19 (1): 50-55.   DOI: 10.1016/j.joim.2020.10.004
Online available: 22 January 2021

Abstract153)   HTML    PDF      

Objective

Traditional Chinese medicine (TCM) has been widely used throughout China to prevent and cure diseases for thousands of years, and now it is a part of the integrative medicine field that is available in Western societies. To ensure the safety and quality of the herbal medicines that are a major part of the TCM tradition, they must be held to modern pharmaceutical standards. Erzhi pill (EZP) is a Chinese Pharmacopeia-listed herbal preparation that is used in the long-term clinical management of post-menopausal symptoms, osteoporosis and menstrual disorders. Until now, whether the drug release mechanism of EZP is in line with its intended TCM usage has not been studied.

Methods

The release of specnuezhenide from three EZPs (self-made, Leiyunshang and Renhe) in simulated gastric fluid (SGF), acetate buffer (pH 4.5 buffer) and simulated intestinal fluid (SIF) was investigated in a dissolution test. The water uptake capacity and erosion extent of the three EZPs were investigated using swelling and erosion studies. The drug release mechanism was further assessed through statistical model fitting, using DDSolver software.

Results

The release of specnuezhenide from all three EZPs in SGF was less than 50% within a 4 h period. However, over 70% of the specnuezhenide was released from each EZP in both pH 4.5 buffer and SIF in the same time. Analysis of the swelling and erosion behaviors and the drug release mechanism of the three EZPs confirmed that the release rate from EZP followed a sustained release profile, which was an interactive combination of swelling and erosion. 

Conclusion

This study showed that the release pattern from the pills was in line with the intended TCM use of EZP. TCM had not only theoretically considered sustained release from the pills, but also formulated them to achieve this release pattern. When establishing quality control standards for pills, the theoretical TCM usage and the actual release patterns need to be considered.


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Aamar-e-Advia (shelf-lives) of drugs in Unani system of medicine: A conceptual review
Ameena Yasmeen, Ghulamuddin Sofi, Kaleemullah Khan
Journal of Integrative Medicine    2020, 18 (2): 114-124.   DOI: 10.1016/j.joim.2020.01.003
Online available: 16 January 2020

Abstract152)   HTML    PDF      
In an era of globalization and increased global demand for herbal medicines, it is essential to ensure the quality and consistency of drugs. Changes in the quality of an herbal product over time should be detectable. The assessments of chemical quality and therapeutic efficacy of herbal drugs are necessary to establish their shelf-lives. Thus, stability testing is needed to establish standards for herbal products. Unani medicine has its own conceptual framework for studying health and disease. The mode of treatment includes Ilaj bit Tadbeer (regimental therapy), Ilaj bil Ghiza (dietotherapy), Ilaj bil Dawa (pharmacotherapy) and Ilaj bil Yad/Jarahat (surgery) as a final option. Ilaj bil Dawa is the most used mode of treatment. The drugs include either crude drugs prepared from plant, animal and mineral sources, called Mufrad(single) drugs or various formulations prepared from these crude drugs, called Murakkab (compound) drugs. To date, stability studies have been carried out on compound drugs, whereas only a few single drugs had had their stability tested. These studies are needed to understand how the quality of an herbal drug varies over the time when it is prepared and consumed. This may also help to standardize procedures for manufacturing compound formulations ab initio. The present study reviews the concept of Aamar-e-Advia (shelf-lives) described in the literature of the Unani system of medicine. Further, various factors that are considered important to assess the shelf-life of Unani drugs are discussed in the context of contemporary protocols for shelf-life assessment.
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Can acupuncture therapy reduce preoperative anxiety? A systematic review and meta-analysis
Qiu-yu Tong, Ran Liu, Kun Zhang, Yuan Gao, Guang-wei Cui, Wei-dong Shen
Journal of Integrative Medicine    2021, 19 (1): 20-28.   DOI: 10.1016/j.joim.2020.10.007
Accepted: 24 July 2020
Online available: 18 November 2020

Abstract152)   HTML    PDF      
Background
Acupuncture therapy has shown promise for effectively relieving preoperative anxiety. Nevertheless, previous findings from randomized controlled trials (RCTs) are inconsistent and must be examined in detail.

Objective
This study systematically evaluates the efficacy and safety of acupuncture therapy for preoperative anxiety as well as the quality of evidence supporting this application.

Search strategy
The China National Knowledge Infrastructure Database, Wanfang Data Journal Database, Chinese Biomedical Literature Database, Chongqing VIP, Embase, PubMed and Cochrane Library Databases were queried from their inception to 19, February 2020, using keywords such as “acupuncture therapy,” “preoperative” and “anxioty.” Manual searches expanded the search breadth and included conference abstracts and other reference lists.

Inclusion criteria
RCTs were included in the current study if they contained a comparison between a group of anxiety patients that received acupuncture therapy and a control group that received sham acupuncture.

Data extraction and analysis
Literature was reviewed, and various articles were selected using the NoteExpress 3.2.0 software. Two researchers independently screened and extracted data and evaluated the risk of bias in the included studies. The RevMan 5.3 software was used for data aggregation and the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) assessment was used to evaluate the quality of the study outcomes.

Results
Twelve studies were included in the review, containing a total of 916 patients. Meta-analysis showed that, compared with the control group, patients who received acupuncture therapy had reduced State-Trait Anxiety Inventory Scale (STAI-S) score (mean difference [MD] = –9.07, 95% confidence interval [CI] [–13.19 to –4.96], P < 0.0001) and Visual Analogue Scale (VAS) score (MD = –1.37, 95% CI [–2.29 to –0.45], P = 0.003). However, for the Hamilton Anxiety Scale (HAMA) score, there was no difference between the two groups (MD = –3.98, 95% CI [–12.89 to 4.92], P = 0.38). Further, the GRADE assessment demonstrated that the STAI-S was of moderate quality, the VAS of low quality and the HAMA of very low quality.

Conclusion
Acupuncture therapy may be able to decrease anxiety in preoperative patients, but the results need to be further verified due to the small sample sizes and the low quality of evidence to date.
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Controversial conclusions from two randomized controlled trials for acupuncture's effects on polycystic ovary syndrome or in vitro fertilization support
Sherman Gu, Arthur Yin Fan
Journal of Integrative Medicine    2020, 18 (2): 89-91.   DOI: 10.1016/j.joim.2020.01.007
Online available: 04 February 2020

Abstract151)   HTML    PDF      
Two reports of trials investigating the potential effect of acupuncture in increasing live birth rate (LBR) in women with polycystic ovary syndrome (PCOS) or those undergoing in vitro fertilization (IVF) were published by Journal of American Medical Association in 2017 and 2018 respectively. The trial investigators did not recommend acupuncture for the women with PCOS or IVF based on their findings. This paper raises the concern that the findings that acupuncture did not increase LBR for women with PCOS or undergoing IVF may be the result of methodological flaws in the studies and unintended bias such as use of an invalid control intervention and underestimation of the true acupuncture effect. Therefore, their findings may not be a valid reflection of acupuncture’s effect in improving LBR in women with these clinical conditions.
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Effects of mild moxibustion on intestinal microbiome and NLRP3 inflammasome in rats with 5-fluorouracil-induced intestinal mucositis
Bing-rong Li, Shi-yun Shao, Long Yuan, Ru Jia, Jian Sun, Qing Ji, Hua Sui, Li-hong Zhou, Yi Zhang, Hui Liu, Qi Li, Yan Wang, Bi-meng Zhang
Journal of Integrative Medicine    2021, 19 (2): 144-157.   DOI: 10.1016/j.joim.2020.12.004
Online available: 13 December 2020

Abstract148)   HTML    PDF      
Objective
The present study investigated how mild moxibustion treatment affects the intestinal microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis (IM) induced with 5-fluorouracil (5-Fu).
Methods
Forty male Sprague-Dawley rats were randomly divided into control, chemotherapy, moxibustion and probiotics groups. The IM rat model was established by intraperitoneal injection of 5-Fu. Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days. Tissue morphology, serum levels of inflammatory factors and the expression levels of tight junction proteins, caspase-1, gasdermin D and NLRP3 were evaluated in colon tissue, through hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay, Western blotting, quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence. Gut microbiome profiling was conducted through 16S rRNA amplicon sequencing.
Results
Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins, reduced cell apoptosis and the expression levels of caspase-1, gasdermin D and NLRP3; they also decreased the serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IL-18, while increasing serum levels of IL-10. Moxibustion and probiotic treatments also corrected the reduction in α-diversity and β-diversity in IM rats, greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapy-treated rats to levels observed in healthy animals. We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors. Finally, moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors.
Conclusion
Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation. Moreover, moxibustion modulates the gut microbiota, likely via decreasing the expression levels of the NLRP3 inflammasome.
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Mindfulness interventions during pregnancy: A narrative review
Leandro Lucena, Cristina Frange, Ana Claudia Amorim Pinto, Monica Levy Andersen, Sergio Tufik, Helena Hachul
Journal of Integrative Medicine    2020, 18 (6): 470-477.   DOI: 10.1016/j.joim.2020.07.007
Accepted: 10 June 2020
Online available: 31 July 2020

Abstract145)   HTML    PDF      
Pregnancy is a period of major transformations in a woman’s life; increased stress, and mood and sleep disorders are frequent. This review evaluates mindfulness interventions during pregnancy and their ability to help manage stress, anxiety, depression, emotional regulation, level of mindfulness and sleep quality. A search of English language scientific literature relevant to mindfulness interventions for pregnant women was conducted using PubMed, Scopus and Web of Science, without restriction on publication date. Inclusion criteria were randomized clinical trials with pregnant women, using mindfulness as an intervention for at least three weeks, in one of our main areas of interest, and using only validated scales to measure outcomes. Two hundred and thirty studies were identified in our searches of research databases, and thirteen were included in our analysis. We found a large diversity of mindfulness programs, heterogeneity among the instruments used to evaluate outcomes, and inconsistency in the gestational periods used in the studies. Mindfulness interventions were beneficial for stress, anxiety and depression. Mindfulness was also effective when applied in pregnant women with a history of depression or experiencing depression. Considering emotional regulation and the level of mindfulness, there were signs of improvement, but more studies are needed. None of the studies evaluated sleep quality. Our review provides information about current mindfulness programs, an overview of the effects of mindfulness interventions, a description of the measurements used so far, and recommendations for developing high-quality mindfulness protocols for pregnant women.
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Letter to the editor regarding "Galen's place in Avicenna's The Canon of Medicine: Respect, confirmation and criticism"
Mostafa Araj-Khodaei, Javad Ghazi Sha'rbaf, Somaiyeh Taheri-Targhi, Reza Mohammadinasab
Journal of Integrative Medicine    2020, 18 (3): 274-274.   DOI: 10.1016/j.joim.2020.03.002
Accepted: 18 March 2020
Online available: 19 March 2020

Abstract145)   HTML    PDF      
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Therapeutic effects of herbal formula Huangqisan on metabolic disorders via SREBF1, SCD1 and AMPK signaling pathway
Ya-lei Liu, Zhen-yu Zhou, Min Gao, Guang Ji, Cheng Huang, Sheng-jie Fan
Journal of Integrative Medicine    2021, 19 (2): 167-176.   DOI: 10.1016/j.joim.2020.11.002
Accepted: 08 May 2020
Online available: 20 November 2020

Abstract142)   HTML    PDF      
Objective
Metabolic syndrome is a complex medical condition that has become an alarming epidemic, but an effective therapy for this disease is still lacking. The use of the herbal formula Huangqisan (HQS) to treat diabetes is documented in the Chinese medical literature as early as 1117 A.D.; however, its therapeutic effects and underlying mechanisms remain elusive.

Methods
To investigate the beneficial effects of HQS on metabolic disorders, high-fat diet-induced obesity (DIO), leptin receptor dysfunction (db/db) and low-density lipoprotein receptor-knockout (LDLR-/-) mice were used. Obese mice were treated with either HQS or vehicle. Blood, liver tissue, white fat tissue and brown adipose tissue were harvested at the end of the treatment. Metabolic disease-related parameters were evaluated to test HQS’s effects against diabetes, obesity and hyperlipidemia. Aortic arches from LDLR-/- mice were analyzed to investigate the effects of HQS on atherosclerosis. RNA-sequence, quantitative real-time polymerase chain reaction and Western blot were performed to investigate the mechanisms of HQS against metabolic disorder.

Results
HQS lowered body weight, fasting blood glucose and serum lipid levels and improved glucose tolerance and insulin sensitivity in DIO mice and db/db mice (P < 0.05). HQS also blocked atherosclerotic plaque formation in LDLR-/- mice. HQS suppressed de novo lipid synthesis by reducing the expression of messenger RNA for sterol regulatory element-binding factor 1, stearyl coenzyme A desaturase 1 and fatty acid synthase, and enhancing adenosine 5'-monophosphate-activated protein kinase signaling in both in vivo and in vitro experiments, indicating potential mechanisms for HQS’s activity against diabetes.

Conclusion
HQS is effective for reversing metabolic disorder and has the potential to be used as therapy for metabolic syndrome.
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Effects of Zataria oxymel on obesity, insulin resistance and lipid profile: A randomized, controlled, triple-blind trial
Jafar Abolghasemi, Mohammad Ali Farboodniay Jahromi, Mohammad Hossein Sharifi, Zohreh Mazloom, Leila Hosseini, Nasrindokht Zamani, Majid Nimrouzi
Journal of Integrative Medicine    2020, 18 (5): 401-408.   DOI: 10.1016/j.joim.2020.06.003
Accepted: 27 November 2019
Online available: 15 June 2020

Abstract140)   HTML    PDF      

Background

Obesity is a major public health problem and its occurrence is markedly increasing in developed and developing countries. However, few studies have investigated the use of natural products to treat obesity. The effects of taking a combination of oxymel and Zataria multiflora Boiss. (ZM), herein referred to as Zataria oxymel (ZO), on obesity, lipid profile and insulin resistance have not yet been studied.


Objective

This study evaluates the effects of oxymel and ZO on obesity, lipid profile and insulin resistance.


Design, setting, participants and interventions
In this randomized, controlled, triple-blind trial, overweight patients were randomly divided into three groups and received doses of study compounds twice per day for twelve weeks. Group A received 0.75 g ZM in 10 mL oxymel in each treatment; group B received 1.5 g ZM in 10 mL of oxymel in each treatment and group C (control) only received 10 mL of oxymel in each treatment.

Main outcome measures
Anthropometric parameters, including body mass index (BMI), waist circumference and hip circumference, were measured at the time of registration. Blood tests were carried out at the beginning and once again at end of the study. Blood parameters included fasting blood sugar (FBS), insulin levels, serum lipid profile (total cholesterol, triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol) and liver enzymes (aspartate transaminase and alanine transaminase). Serum creatinine was also measured at the beginning of the project and in monthly intervals for three months. The homeostasis model assessment index was calculated as fasting insulin (μIU/mL) × FBS (mg/dL)/405.

Results
The results showed that patients receiving ZO experienced significant reduction in waist circumference in groups A, B and C, respectively (P < 0.001) but no significant change in BMI. Group A also experienced reduction in hip circumference (P = 0.01). Groups B and C had reduction in the homeostatic model assessment of insulin resistance (P = 0.05 and P = 0.01, respectively), with no significant reduction in FBS. No effect on lipid profile, liver enzymes or serum creatinine was observed in the three groups.

Conclusion
In this study, treatment with ZO and oxymel reduced insulin resistance, and waist and hip circumferences in overweight patients. Nonetheless, the traditional Persian use of ZO as a beverage to improve the anthropometric indices in overweight individuals still requires further research with a larger sample size.
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Consensus views on competencies and teaching methods for an interprofessional curriculum on complementary and integrative medicine: A Delphi study
Angelika Homberg, Katja Krug, Nadja Klafke, Katharina Glassen, Cornelia Mahler, Svetla Loukanova
Journal of Integrative Medicine    2021, 19 (3): 282-290.   DOI: 10.1016/j.joim.2021.03.001
Accepted: 03 February 2021
Online available: 11 March 2021

Abstract138)   HTML    PDF      
Objective
A collaborative team is necessary to help patients achieve their healthcare goals using complementary medicine. At present, healthcare professionals do not feel sufficiently qualified to provide this service. This study sought to identify competencies and teaching methods for interprofessional training on complementary and integrative medicine at medical schools.

Methods
Sixty-five German-speaking experts with various professional backgrounds were invited to take part in a three-round Delphi study. In the first round, predefined competencies were assessed on a seven-point Likert scale, and participants were invited to propose additional competencies that would be evaluated in the subsequent rounds. The competencies were ranked based on the participant assessments and were assigned to four relevance groups. In the second and third rounds, suitable teaching methods were identified using free-text fields and multiple-choice questions. In a final workshop, participants synthesized the outcomes of the previous sessions and derived key competencies that would be a benefit to undergraduate interprofessional training in complementary and integrative medicine at medical schools.

Results
The three rounds plus final worksop were attended by 50, 40, 36 and 11 experts. The competencies that these experts determined to be highly relevant to teaching complementary and integrative medicine emphasized, in particular, the respectful treatment of patients and the importance of taking a medical history. From these highly relevant competencies, three key targets were agreed upon in the final workshop: students are able to 1) classify and assess complementary medical terms and methods; 2) work collaboratively and integrate patients into the interprofessional team; 3) involve patients and their relatives respectfully and empathetically in all healthcare processes. To achieve these competency goals, the following teaching methods were highlighted: students discuss therapy options based on authentic patient cases with each other and practice empathic patient communication incorporating complementary medicine. Further, the theoretical background of complementary medicines could be provided as online-training, to use the class sessions for hands-on exercises and interprofessional exchange and discussion.

Conclusion
Despite the heterogeneous panel of experts, a consensus was reached on the competency orientation and teaching approaches. The results can promote the implementation of interprofessional training for complementary medicine in undergraduate education.
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Calcarea carbonica treatment rescues lipopolysaccharide-induced inflammatory response in human mononuclear cells via downregulation of inducible cyclooxygenase pathway
Swatantra Kumar, Vimal K Maurya, Debadatta Nayak, Anil Khurana, Raj K Manchanda, Srinivasulu Gadugu, Madan LB Bhatt, Shailendra K Saxena
Journal of Integrative Medicine    2020, 18 (5): 441-449.   DOI: 10.1016/j.joim.2020.06.001
Accepted: 03 June 2020
Online available: 03 June 2020

Abstract135)   HTML    PDF      

Objective

Prolonged use of nonsteroidal anti-inflammatory drugs is associated with severe side effects and toxicity. Therefore, we studied the anti-inflammatory role of Calcarea carbonica which had minimal toxicity at the low doses. 


Methods

THP-1 human mononuclear cells were treated with C. carbonica to evaluate the 50% cytotoxicity concentration (CC50) and 50% effective concentration (EC50). Cell survival was evaluated in lipopolysaccharide-stimulated C. carbonica-treated cells. Nitric oxide (NO) and tumor necrosis factor-α (TNF-α) were measured to evaluate the anti-inflammatory activity of C. carbonica. Cyclooxygenase-2 (COX-2) protein expression was determined by Western blotting analysis, and the interaction of C. carbonica with the COX-2 protein was evaluated using molecular docking simulation. 


Results

The CC50 and EC50 of C. carbonica were found to be 43.26 and 11.99 μg/mL, respectively. The cell survival assay showed a 1.192-fold (P = 0.0129), 1.443-fold (P = 0.0009) and 1.605-fold (P = 0.0004) increase in cell survival at 24, 48 and 72 h after initiating C. carbonica treatment, respectively. C. carbonica-treated cells showed a reduction in NO levels by 2.355 folds (P = 0.0001), 2.181 folds (P = 0.0001) and 2.071 folds (P = 0.0001) at 24, 48 and 72 h, respectively. The treated cells also showed a reduction in TNF-α levels by 1.395 folds (P = 0.0013), 1.541 folds (P = 0.0005) and 1.550 folds (P = 0.0005) at 24, 48 and 72 h, respectively. In addition, a 1.193-fold reduction (P = 0.0126) in COX-2 protein expression was found in C. carbonica-treated cells. The simulated molecular docking showed interaction of C. carbonica with the phenylalanine 367 residue present in COX-2’s active site. 


Conclusion

C. carbonica exhibited anti-inflammatory properties in lipopolysaccharide-stimulated cells by significantly reducing NO production and TNF-α level through downregulation of the COX-2 protein. This effect is probably mediated through interaction of C. carbonica with the phenylalanine 367 residue present in COX-2’s active site.

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Treatment of pulmonary fibrosis in one convalescent patient with corona virus disease 2019 by oral traditional Chinese medicine decoction: A case report
Na Zhi, Qian Mo, Shuo Yang, Yuan-xing Qin, Hao Chen, Zeng-guang Wu, Cai-hong Lan, Jun Zhang, Yin-long Li
Journal of Integrative Medicine    2021, 19 (2): 185-190.   DOI: 10.1016/j.joim.2020.11.005
Accepted: 30 September 2020
Online available: 18 November 2020

Abstract134)   HTML    PDF      
After one-month of oral treatment with traditional Chinese medicine decoction, without using other drugs, the lung inflammatory exudate, pulmonary fibrosis and quality of life of a 61-year-old female patient with corona virus disease 2019 (COVID-19) were significantly improved. No recurrence or deterioration of the patient’s condition was found within seven weeks of treatment and follow-up, and no adverse events occurred, indicating that oral Chinese medicine decoction was able to improve the pulmonary inflammation and fibrosis in a patient recovering from COVID-19, but further research is still needed.
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Carpobrotus edulis (L.) N.E.Br. extract as a skin preserving agent: from traditional medicine to scientific validation
Miriam Bazzicalupo, Laura Cornara, Bruno Burlando, Alberta Cascini, Marcella Denaro, Antonella Smeriglio, Domenico Trombetta
Journal of Integrative Medicine    2021, 19 (6): 526-536.   DOI: 10.1016/j.joim.2021.09.002
Online available: 30 September 2021

Abstract132)   HTML    PDF      

Objective

Carpobrotus edulis (L.) N.E.Br. is a succulent perennial plant native to South Africa and grows invasively in the Mediterranean basin. It is commonly used for the treatment of various diseases, including skin wound healing and regeneration, for which experimental validation is lacking. We therefore evaluated the skin healing properties of C. edulis by testing an C. edulis aqueous leaf extract (CAE) on cell cultures and in enzymatic assays.

Methods

Micro-morphological analysis of leaves was carried out using scanning electron microscopy and epifluorescence microscopy. Phytochemical features and antioxidant activity of CAE were evaluated by reversed-phase liquid chromatography coupled with diode array detection and electrospray ion trap mass spectrometry (RP-LC-DAD-ESI-MS), and in vitro cell-free assays. Biological activities were evaluated using keratinocytes and fibroblasts, as well as elastase, collagenase, and hyaluronidase.

Results

CAE showed high carbohydrates (28.59% ± 0.68%), total phenols ([101.9 ± 6.0] g gallic acid equivalents/kg dry extract [DE]), and flavonoids ([545.9 ± 26.0] g rutin equivalents/kg DE). RP-LC-DAD-ESI-MS revealed the predominant presence of hydroxycinnamic acids (51.96%), followed by tannins (14.82%) and flavonols (11.32%). The extract was not cytotoxic, had a strong and dose-dependent antioxidant activity, and inhibited collagenase (> 90% at 500 μg/mL) and hyaluronidase (100% at 1000 μg/mL). In cell culture experiments, CAE increased wound closure and collagen production, which was consistent with its high polyphenol content. 

Conclusion

Our data support the use of the C. edulis for skin care and the treatment of skin problems. Moreover, use of C. edulis for skin care purposes could be an eco-friendly solution to reduce its invasiveness in the environment.

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Use of complementary and alternative medicine in general population during COVID-19 outbreak: A survey in Iran
Mahlagha Dehghan, Alireza Ghanbari, Fatemeh Ghaedi Heidari, Parvin Mangalian, Mohammad Ali Zakerid
Journal of Integrative Medicine    2022, 20 (1): 45-51.   DOI: 10.1016/j.joim.2021.11.004
Accepted: 13 July 2021
Online available: 16 November 2021

Abstract132)   HTML    PDF      
Objective
Some epidemic diseases such as coronavirus disease 2019 (COVID-19) have caused many physical, psychological, and social challenges, despite the existence of treatment strategies. Many people are looking for complementary and alternative medicine (CAM) to prevent such diseases. The present study was performed to determine how some types of CAM were being used during the COVID-19 epidemic in Iran.

Methods
The present study had a cross-sectional descriptive correlational design. All Iranian residents above 17 years old were eligible to participate in the study. A total of 782 participants completed a demographic information questionnaire, a questionnaire about their use of CAMs and a questionnaire about their satisfaction with the CAMs they used. Web-based sampling was conducted from 20 April 2020 to 20 August 2020.

Results
Of the participants, 84% used at least one type of CAM during the COVID-19 outbreak. The most used CAMs were dietary supplements (61.3%), prayer (57.9%), and herbal medicines (48.8%). The majority of the participants (50%–66%) have used CAMs to prevent the transmission of COVID-19 or to reduce anxiety caused by the COVID-19 pandemic. CAM use was associated with sex, having children, place of residence, COVID-19 status, and source of gathering information about CAM (P < 0.05). All 32 participants who had been infected with COVID-19 used at least one type of CAM for treatment or alleviation of the disease symptoms.

Conclusion
During the COVID-19 outbreak, some types of CAM, particularly nutritional supplements, medicinal herbs, and prayer, were commonly used to prevent COVID-19 and reduce pandemic-related anxiety.
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Comparable effects of Jiedu granules and sorafenib for advanced hepatocellular carcinoma: A prospective multicenter cohort study
He-tong Zhao, Yong-bin Meng, Xiao-feng Zhai, Bin-bin Cheng, Sha-sha Yu, Man Yao, Hui-xia Yin, Xu-ying Wan, Yun-ke Yang, Hui Liu, Feng Shen, Chang-quan Ling
Journal of Integrative Medicine    2020, 18 (4): 319-325.   DOI: 10.1016.j.joim.2020.05.003
Accepted: 15 April 2020
Online available: 15 May 2020

Abstract131)   HTML    PDF      

Objective

The drug sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma (HCC). Chinese herbal medicine has also been used to manage advanced HCC. The present work evaluates the effectiveness and safety of Jiedu (JD) granules, a compound of traditional Chinese herbal medicines, side-by-side with sorafenib for the treatment of advance HCC.

Methods

Patients with advanced HCC were enrolled in this study during December 2014 and March 2018. Study patients were elected to receive treatment with JD granules or sorafenib. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and safety. Propensity score matching (PSM) analysis was used to control for possible selection bias from the study group allocation process.

Results

Of the 325 patients included in this study, 161 received JD granules and 164 received sorafenib. No significant differences were found in OS or PFS among patients receiving JD granules compared to sorafenib (P > 0.05). Median OS of the two study groups was 6.83 months (95% confidence interval [CI]: 5.83–9.47) in the group receiving JD granules and 8 months (95% CI: 6.67–9.80) in the group receiving sorafenib, with half-, 1-, and 2- year survival rates of 53.6%, 31.2% and 13.2% vs 60.1%, 35.5% and 14.2%, respectively. Even after PSM, the median survival time did not differ between the JD granules group (9.03 months; 95% CI: 6.37–14.2) and the sorafenib group (7.93 months; 95% CI: 6.5–9.97), with comparable half-, 1- and 2-year survival rates. The most common adverse events (AEs) were diarrhea (13.7%) and fatigue (5.6%) in the JD granules group, and hand-foot skin reaction (46.3%) and diarrhea (36.6%) in the sorafenib group. The JD granules was more cost-effective than sorafenib treatment for advanced HCC.

Conclusion

Compared to sorafenib, JD granules provided a comparable treatment for HCC that was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC. 


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Women's preconception health patterns in traditional Chinese medicine as a predictor of fertility outcomes
Xia-qiu Wu, Wendy Satmary, Jin Peng, Ka-kit Hui
Journal of Integrative Medicine    2020, 18 (3): 222-228.   DOI: 10.1016/j.joim.2020.01.006
Online available: 26 January 2020

Abstract130)   HTML    PDF      
Objective
To examine the association between traditional Chinese medicine (TCM), preconception health patterns and fertility outcomes.

Methods
A community-based prospective cohort study was conducted in China. A total of 3012 newly married women who were willing to conceive within 2 years were enrolled in the study and took National Free Prepregnancy Checkups (NFPC). A reliably structured self-rating scale was used to measure the TCM preconception health patterns of the enrolled women. A 3-year follow-up was conducted to obtain the fertility outcomes, including pregnancy rate, time to pregnancy, spontaneous miscarriage and newborn status. Statistical analyses were conducted using Chi-square or Fisher’s exact tests, logistic regression models, general linear models and the Cox proportional hazard model.

Results
The fertility outcomes showed no statistic correlations to the terms of NFPC in this population. Approximately a half of the women (46.66%) had unhealthy patterns. Women with qi & blood-deficiency (odds ratio [OR] = 35.19, 95% confidence interval [CI] = 1.55–801.15) or qi-stagnation (OR = 4.55, 95% CI = 0.90–23.06) pattern took a longer time to get pregnant, and those with qi-stagnation (OR = 2.05, 95% CI = 1.1–3.82) or yang-deficiency (OR = 1.91, 95% CI = 1.12–3.25) pattern had a higher risk of spontaneous miscarriage.

Conclusion
Three unhealthy TCM patterns during the preconception period might be risk factors for low fecundity or poor pregnancy outcomes. The TCM preconception pattern identification may provide a convenient and effective way to screen for potential pregnancy risks beyond the NFPC. Further, appropriate interventions based on the TCM preconception health patterns are needed to improve quality in women’s fecundability and birth outcomes.

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ISSN 2095-4964
CN 31-2083/R

Editors-in-Chief:
Lixing Lao, Virginia, USA
Frequency: 6 issues per year
Publisher: Science Press, China

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