The processing of Chinese herbal medicine is a form of pharmaceutical technology developed over thousands of years, in order to increase efficiency and decrease toxicity of herbs in traditional Chinese medicine (TCM). Herbal processing is essential for safe and effective application of TCM in clinical practice, as it alters the active chemical components and therefore the functions of herbal medicines. Alkaloid-rich herbal medicines in TCM are commonly processed by cleansing, cutting, processing by dry stir-frying, stir-frying with liquid adjuvants, and processing by water decoction. In addition, commonly used adjuvants for processing alkaloid-rich herbal medicines are river sand, wine, vinegar, brine, honey and herbal juice. For alkaloid-rich herbal medicines, the main chemical reactions that occur during processing include hydrolysis, oxidation, replacement, decomposition and condensation. This paper aimed to summarize the processing methods and mechanisms for alkaloid-rich Chinese herbal medicines, and provide much-needed theoretical support and scientific evidence for understanding those mechanisms and effects. Information on processing methods for alkaloid-rich herbal medicines was collected from classic books of herbal medicine, PhD and MSc dissertations, online scientific databases including PubMed, SciFinder, Scopus, Web of Science, Baidu Scholar and Google Scholar. This paper should help to advance our knowledge of the processing mechanisms and aid in the development of processing methods for alkaloid-rich Chinese herbal medicines.

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% (P = 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.

Background

Depression in patients with Parkinson’s disease (dPD) is related closely to quality of life. Current studies have suggested that Pingchan granule (PCG) might be effective for treating dPD.

Objective

This study determines the efficacy of PCG for depressive symptoms in Parkinson’s disease (PD).

Design, setting, participants and interventions

This was a randomized, double-blind, placebo-controlled trial, conducted in Longhua Hospital, Shanghai, China. Patients diagnosed with idiopathic PD and clinically significant depressive symptoms (defined by a 24-item Hamilton Rating Scale for Depression [HAM-D] score ≥ 8) were included in this study, followed for 24 weeks and randomly assigned to PCG or placebo treatment groups in a 1:1 ratio.

Main outcome measures

The primary outcome was the change from baseline to week 24 in HAM-D score among the set of patients who completed the study following the treatment protocol (per-protocol set). Secondary outcomes included changes in scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) part 2 (UPDRS-II), UPDRS part 3 (UPDRS-III), Parkinson’s Disease Sleep Scale (PDSS) and Hamilton Rating Scale for Anxiety (HAM-A), between baseline and week 24.

Results

Eighty-six patients were enrolled, and 85 patients were included in the per-protocol set. HAM-D scores decreased by an adjusted mean of 11.77 (standard error [SE] 0.25) in the PCG group and 3.86 (SE 0.25) in the placebo group (between-group difference = 7.91, 95% confidence interval [7.22, 8.80], P < 0.001), in the multivariable linear regression. Improvements in scores on the UPDRS-II, UPDRS-III, PDSS, and HAM-A scales were also observed.

Conclusion

Treatment with PCG was well tolerated and improved depressive symptoms and motor and other non-motor symptoms in PD.

Trial registration

Chinese Clinical Trial Register, ChiCTR-INR-17011949.

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.

Objective

Bushen Tiansui formula (BSTSF), a traditional Chinese medicine prescription, has been widely used to treat Alzheimer’s disease (AD). However, the mechanisms underlying its effects remain largely unknown. In this study, a rat AD model was used to study the effects of BSTSF on cognitive performance and expression of transfer RNA-derived small RNAs (tsRNAs) in the hippocampus, to determine whether treatment of AD with BSTSF could regulate the expression of tsRNAs, a novel small non-coding RNA.

Methods

To generate a validated AD model, oligomeric amyloid-β1-42 (Aβ1-42) was injected intracerebroventricularly into rats. The Morris water maze (MWM) test was used to evaluate rat cognitive performance, and tsRNA-sequencing was conducted to examine tsRNA expression in the rat hippocampus. Potential targets were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatic analyses were conducted to investigate the biological function of candidate tsRNAs.

Results

The learning and memory deficits of Aβ1–42-induced AD rats, assessed by MWM tests, were clearly ameliorated by BSTSF treatment. A total of 387 tsRNAs were detected in the rat hippocampus. Among them, 13 were significantly dysregulated in AD rats compared with sham control rats, while 57 were markedly altered by BSTSF treatment, relative to untreated AD rats (fold change ≥ 2 and P < 0.05). Moreover, six BSTSF treatment-related tsRNAs were identified and validated by qRT-PCR. Bioinformatic analyses indicated that the six treatment-related tsRNAs had potential therapeutic roles, via multiple signaling pathways and Gene Ontology biological functions, including cyclic adenosine monophosphate and retrograde endocannabinoid signaling.

Conclusion

This study identified a previously uncharacterized mechanism underlying the effects of BSTSF in alleviating the learning and memory deficits in Aβ1–42-induced AD rats, demonstrating that tsRNAs are potential therapeutic targets of BSTSF in the treatment of AD.

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.

Objective
This study tests whether long-term intake of Allium tuberosum (AT) can alleviate pulmonary inflammation in ovalbumin (OVA)-induced asthmatic mice and evaluates its effect on the intestinal microbiota and innate lymphoid cells (ILCs).

Methods
BALB/c mice were divided into three groups: phosphate buffer saline, OVA and OVA + AT. The asthmatic murine model was established by sensitization and challenge of OVA in the OVA and OVA + AT groups. AT was given to the OVA + AT group by oral gavage from day 0 to day 27. On day 28, mice were sacrificed. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin, and periodic acid-Schiff staining. The levels of IgE in serum, interleukin-5 (IL-5) and IL-13 from bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The ILCs from the lung and gut were detected by flow cytometry. 16S ribosomal DNA sequencing was used to analyze the differences in colon microbiota among treatment groups.

Results
We found that long-term intake of AT decreased the number of inflammatory cells from BALF, reduced the levels of IL-5 and IL-13 in BALF, and IgE level in serum, and rescued pulmonary histopathology with less mucus secretion in asthmatic mice. 16S ribosomal DNA sequencing results showed that AT strongly affected the colonic bacteria community structure in asthmatic mice, although it had no significant effect on the abundance and diversity of the microbiota. Ruminococcaceae and Desulfovibrionaceae were identified as two biomarkers of the treatment effect of AT. Moreover, AT decreased the numbers of ILCs in both the lung and gut of asthmatic mice.

Conclusion
The results indicate that AT inhibits pulmonary inflammation, possibly by impeding the activation of ILCs and adjusting the homeostasis of gut microbiota in asthmatic mice.

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.

Objective

Ganoderma lucidum spore (GLS) is gaining recognition as a medicinal part of G. lucidum and has been reported to possess various pharmacological properties, such as antitumor activity. In this work, wall-broken GLS powder (BGLSP) and wall-removed GLS powder (RGLSP), two kinds of GLS powder with different manufacturing techniques, were compared in terms of contents of active constituents and in vivo and in vitro antitumor effects.

Methods

The ultraviolet and visible spectrophotometry method was used to determine the contents of polysaccharides and total triterpenoids in BGLSP and RGLSP. Seventeen individual triterpenoids were further quantified using ultra-high-performance liquid chromatography and quantitative analysis of multi-components by single marker. The antitumor effects of BGLSP and RGLSP were evaluated using in vitrocell viability assay against human gastric carcinoma SGC-7901, lung carcinoma A549 and lymphoma Ramos and further validated by in vivo zebrafish xenograft models with transplanted SGC-7901, A549 and Ramos.

Results

The results showed that the contents of polysaccharides, total triterpenoids and individual triterpenoids of RGLSP were significantly higher than those of BGLSP. Although both BGLSP and RGLSP inhibited the three tumor cell lines in vitro in a dose-dependent manner, the inhibitory effects of RGLSP were much better than those of BGLSP. In the in vivo zebrafish assay, RGLSP exhibited more potent inhibitory activities against tumors transplanted into the zebrafish compared with BGLSP, and the inhibition rates of RGLSP reached approximately 78%, 31% and 83% on SGC-7901, A549 and Ramos, respectively. 

Conclusion

The results indicated that the antitumor effects of GLS were positively correlated with the contents of the polysaccharides and triterpenoids and demonstrated that the wall-removing manufacturing technique could significantly improve the levels of active constituents, and thereby enhance the antitumor activity.

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.