Curcumin is a widely studied natural compound which has shown tremendous in vitro therapeutic potential. Despite that, the clinical efficacy of the native curcumin is weak due to its low bioavailability and high metabolism in the gastrointestinal tract. During the last decade, researchers have come up with different formulations with a focus on improving the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with the varying range of enhanced bioavailability. The purpose of this review is to collate the published clinical studies of curcumin products with improved bioavailability over conventional (unformulated) curcumin. Based on the literature search, 11 curcumin formulations with available human bioavailability and pharmacokinetics data were included in this review. Further, the data on clinical study design, analytical method, pharmacokinetic parameters and other relevant details of each formulation were extracted. Based on a review of these studies, it is evident that better bioavailability of formulated curcumin products is mostly attributed to improved solubility, stability, and possibly low first-pass metabolism. The review hopes to provide a quick reference guide for anyone looking information on these bioavailable curcumin formulations. Based on the published reports, NovaSol^?(185), CurcuWin^? (136) and LongVida^? (100) exhibited over 100-fold higher bioavailability relative to reference unformulated curcumin. Suggested mechanisms accounting for improved bioavailability of the formulations and details on the bioanalysis methods are also discussed.

Thyroid dysfunction, affecting people of all ages, not only damages human growth and energy metabolism but is also comorbid with other illnesses such as cardiovascular disease, kidney disease and gastrointestinal disorders. With the increasing acceptance of alternative and complementary therapies, acupuncture, a traditional Chinese medical practice, has also been employed to address this problem. Analysing 29 clinical projects that were retrieved from 29 major digital databases and include 1757 patients aged 7–79?years from China, Italy, Korea, Macedonia and Russia, this narrative review offers an overview of the efficacy, and evaluated the safe and cost-effective use of acupuncture against hyperthyroidism, hypothyroidism and thyroid-relevant illnesses. Findings indicated reductions in patient symptoms and improvements in biomarkers where acupuncture was used alone or in combination therapy. In addition to showing the role of acupuncture as an alternative and complementary medicine or as an adjunctive therapy for curative and rehabilitative purposes, more well-designed researches are needed to achieve reliable data.

Background
Vulvodynia, or vulvar pain, is a common condition in women; however, there are few evidence-based clinical trials evaluating nonpharmacological therapies for this condition. Acupuncture is one complementary and integrative medicine therapy used by some patients with vulvodynia. This study evaluates two different acupuncture strategies for the treatment of vulvodynia and aims to evaluate whether either of the acupuncture protocols reduces vulvar pain, pain duration or pain with intercourse. The study also examines how long the effect of acupuncture lasts in women with vulvodynia.

Methods/design

The study is designed as a randomized controlled trial, focused on two acupuncture protocols. Fifty-one patients who have had vulvodynia for more than 3?months will be recruited. Among them, 34 patients will be randomized into Groups 1a and 1b; those who are unwilling to receive acupuncture will be recruited into the standard care group (Group 2). Patients in Group 1a will have acupuncture focused on the points in the pudendal nerve distribution area, while patients in Group 1b will receive acupuncture focused on traditional (distal) meridian points. Patients in Group 2 will receive routine conventional treatments, such as using pain medications, local injections and physical therapies or other nonsurgical procedures. Acupuncture will last 45?min per session, once or twice a week for 6?weeks. The primary outcome measurement will be objective pain intensity, using the cotton swab test. The secondary outcome measurement will be subjective patient self-reported pain intensity, which will be conducted before cotton swab test. Pain intensities will be measured by an 11-point Numeric Pain Rating Scale. Pain duration and pain score during intercourse are recorded. Local muscle tension, tenderness and trigger points (Ashi points) are also recorded. All measurements will be recorded at baseline (before the treatment), at the end of each week during treatment and at the end of the 6?weeks. Follow-up will be done 6?weeks following the last treatment.

Discussion

Results of this trial will provide preliminary data on whether acupuncture provides better outcomes than nonacupuncture treatments, i.e., standard care, and whether acupuncture focused on the points in pudendal nerve distribution, near the pain area, has better results than traditional acupuncture focused on distal meridian points for vulvodynia.

Trial Registration: 

Clinicaltrials.gov: NCT03481621. Register: March 29, 2018.

Objective
Increasing numbers of cancer patients are using Chinese herbs (CHs). However, differences among prior studies make it difficult to draw firm conclusions about the clinical usefulness of any specific CH formula. The primary objective of this study was to establish the acceptability of taking a standardized CH formula for patients with advanced lung cancer. The secondary objective was to identify any toxicities attributable to this CH formula and to measure changes in quality of life.

Methods

A single-arm, prospective study of a 6-week intervention with a selected CH formula in 15 patients with stage 4 nonsmall-cell lung cancer (NSCLC, Seventh American Joint Committee on Cancer TNM staging system).

Results

Patients with advanced lung cancer were interested in using the CH formula. Completion (93%) and adherence (98%) levels were very high and most patients perceived the CH treatment as easy to take and were willing to take the CHs used in the study again if it was available. About half of the patients reported adverse events, all of which were mild (Grade 1 or 2) and only a small minority (8%) were potentially related to CHs. No biochemical or hematological evidence of toxicity was observed. Overall, there were improvement in quality of life, and reduced feelings of tiredness and sleepiness.

Conclusion

This study provides preliminary evidence that short-term use of a carefully selected and prepared CH formula in patients with stage 4 NSCLC is acceptable and safe.

Objective
The present study aimed to evaluate the analgesic and anti-inflammatory effects of far infrared-emitting ceramics (cFIRs) in a model of persistent inflammatory hyperalgesia and to elucidate the possible mechanisms of these effects.
Methods
Mice were injected with complete Freund’s adjuvant (CFA) and treated with cFIRs via placement on a pad impregnated with cFIRs on the bottom of the housing unit for different periods of time. Mice underwent mechanical hyperalgesia and edema assessments, and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-10 levels were measured. Twenty-four hours after CFA injection and 30?min before cFIR treatment, mice were pretreated with a nonselective adenosinergic antagonist, caffeine, the selective adenosine receptor A1 antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), the selective cannabinoid receptor type 1 antagonist, AM281, the selective cannabinoid receptor type 2 antagonist, AM630, or the nonselective opioid receptor antagonist, naloxone, and mechanical hyperalgesia was assessed.
Results
cFIRs statistically (P?<?0.05) decreased CFA-induced mechanical hyperalgesia ((82.86?±?5.21)% in control group vs (56.67?±?9.54)% in cFIR group) and edema ((1699.0?±?77.8) μm in control group vs (988.7?±?107.6)?μm in cFIR group). cFIRs statistically (P?<?0.05) reduced TNF-α ((0.478?±?0.072)?pg/mg of protein in control group vs (0.273?±?0.055)?pg/mg of protein in cFIR group) and IL-1β ((95.81?±?3.95)?pg/mg of protein in control group vs (80.61?±?4.71)?pg/mg of protein in cFIR group) levels and statistically (P?<?0.05) increased IL-10 ((18.32?±?0.78)?pg/mg of protein in control group vs (25.89?±?1.23)?pg/mg of protein in cFIR group) levels in post-CFA-injected paws. Peripheral pre-administration of inhibitory neuroreceptor antagonists (caffeine, DPCPX, AM281, AM630 and naloxone) prevented the analgesic effects of cFIRs (P?<?0.05).
Conclusion
These data provide additional support for the use of cFIRs in the treatment of painful inflammatory conditions and contribute to our understanding of the neurobiological mechanisms of the therapeutic effects of cFIRs.

Objective
In the present study, we evaluated the effects of the aqueous extract of Physalis angulata root (AEPa) on Leishmania infantum proliferation, morphology, and the driving mechanism in leishmanicidal activity and modulatory action on macrophages.
Methods
L. infantum promastigotes were treated with 50 and 100?μg/mL AEPa for 72?h and then antipromastigote assay was performed by counts in a Newbauer chamber, morphological changes were analyzed by transmission electron microscopy and the mechanism of the leishmanicidal activity was detected. In addition, macrophages were infected with L. infantum and were used to evaluate anti-amastigote activity of AEPa and effects of AEPa on cytokine secretion after 72-hour treatment.
Results
Treatment with AEPa reduced the numbers of L. infantum promastigotes (50% inhibitory concentration (IC₅₀)?=?65.9?μg/mL; selectivity index (SI)?=?22.1) and amastigotes (IC50?=?37.9?μg/mL; SI?=?38.5) compared with the untreated control. Amphotericin B reduced 100% of the promastigote numbers after 72?h of treatment (IC₅₀?=?0.2?μg/mL). AEPa induced several morphological changes and increased the production of reactive oxygen species and apoptotic death in promastigotes after treating for 72?h. AEPa (100?μg/mL) promoted tumor necrosis factor-α secretion in macrophages infected with L. infantum after 72?h of treatment, but did not induce an increase in this cytokine in noninfected macrophages. In addition, AEPa showed no cytotoxic effect on J774-A1 cells (50% cytotoxic concentration >1000?μg/mL).
Conclusion
AEPa presented antileishmanial activity against the promastigotes and amastigotes of L. infantum without macrophage cytotoxicity; these results show that natural products such as P. angulata have leishmanicidal potential and in the future may be an alternative treatment for leishmaniasis.

Objective
Kanchnar guggulu is a compound Ayurvedic formulation used in clinical practice for the treatment of benign and malignant tumors. The present study investigates its cytotoxic and antiproliferative activities.
Methods
The hydro-alcoholic (50%) extract of kanchnar guggulu was prepared. Its antimitotic activity was assessed in an Allium cepa assay, while its antiproliferative effects were studied in a yeast proliferation model. Methotrexate was used as a standard anticancer agent.
Results
In the Allium assay, all concentrations of the extract (1, 2 and 3?mg/mL) and methotrexate (0.02?mg/mL) significantly inhibited the division of A. cepa root cells, decreasing root growth and mitotic index compared to control; this effect was concentration-dependent for kanchnar guggulu extract. In the antiproliferative studies, treatment with the hydro-alcoholic extract of kanchnar guggulu (1, 5 and 10?mg/mL) and methotrexate (0.025, 0.05 and 0.1?mg/mL) resulted in marked reduction of dividing Saccharomyces cerevisiae cells and inhibition of cell viability compared to control. The cytotoxicity of the hydro-alcoholic extract of kanchnar guggulu, shown by its antimitotic and antiproliferative effects, may be due to the presence of flavonoids and phenolics.
Conclusion
Kanchnar guggulu exhibited a cytotoxic effect by inhibiting cell division (antimitotic) and reducing cell proliferation. These results substantiate its potential for the treatment of cancer and support its traditional use in the treatment of cancer.

Objective
Acupuncture has a definite therapeutic effect on chronic obstructive pulmonary disease (COPD), and the cholinergic anti-inflammatory pathway (CAP) has been shown to be involved in regulation of inflammation. In this study, we investigated whether electro-acupuncture (EA) affects the CAP in COPD.
Methods
Sprague–Dawley rats were induced into COPD through exposure to cigarette smoke combined with lipopolysaccharide. EA treatment was applied at Zusanli (ST36) and Feishu (BL13) points for 30?min/d for 7?d. Seventy-two rats were randomly divided into six study groups, including normal, normal?+?EA, normal?+?α-bungarotoxin (α-BGT) (the antagonist of the nicotinic acetylcholine receptor α7 subunit (α7nAChR))?+?EA, COPD, COPD?+?EA, and COPD?+?α-BGT?+?EA. Lung function, pathology and vagus nerve discharge were tested. The levels of acetylcholine (ACh), acetylcholinesterase (AChE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) and lung tissue were measured by enzyme-linked immunosorbent assay. The mRNA and protein expression and immunoreactivity of α7nAChR and its postreceptor inflammation signal pathway, including janus kinase 2 (JAK2), signal transducers and activators of transcription 3 (STAT3), nuclear factor-κB (NF-κB), were observed by quantitative reverse transcription-polymerase chain reaction, Western blot and immunohistochemistry.
Results
Compared with normal rats, there were a significant decline in lung function and discharge of the vagus nerve (P?<?0.01), a marked sign of lung inflammation and an increase of ACh, AChE, IL-6 and TNF-α level in BALF or lung tissue (P?<?0.05, P?<?0.01) and higher expression of α7nAChR, JAK2, STAT3 and NF-κB (P?<?0.05, P?<?0.01) in the COPD rats. In rats receiving EA, the lung function and vagal discharge were enhanced (P?<?0.01), lung inflammation was improved and the levels of ACh, AChE, IL-6 and TNF-α were decreased (P?<?0.01). Further, the expression of α7nAChR, JAK2, STAT3 and NF-κB was downregulated (P?<?0.05, P?<?0.01). However, the above effects of EA were blocked in rats injected with α-BGT (P?<?0.01).
Conclusion
EA treatment can reduce the lung inflammatory response and improve lung function in COPD, which may be related to its involvement in the regulation of CAP.

Objective
The leaves of Chromolaena odorata, a highly invasive shrub found growing wild worldwide, are traditionally used for wound healing. Due to its high flavonoid contents, we aimed to find a new application for this plant. Preliminary tests using its ethanolic leaf extract showed that it could suppress the accumulation of lipids in adipocytes. We therefore studied the anti-adipogenic effect of several C. odorata leaf extracts and the relationship between molecular structure and bio-activity of its isolated flavonoid constituents using 3T3-L1 preadipocytes/adipocytes as a model.
Methods
Three leaf extracts and thirteen flavonoids isolated from C. odorata were tested for their effect on lipid accumulation in 3T3-L1 adipocytes using AdipoRed reagent, with quercetin as the positive control. The effects of active flavonoids on the adipocytes were confirmed by oil red O staining and visualized under a light microscope.
Results
n-Hexane and ethyl acetate extracts of C. odorata leaves displayed anti-adipogenic activity. The latter extract was the more potent one, especially at 40?μg/mL. Four flavonoids, pectolinarigenin, kaempferide, 4,2′-dihydroxy-4′,5′,6′-trimethoxychalcone and dillenetin, exhibited significant, concentration-dependent inhibitory effects on lipid accumulation in 3T3-L1 adipocytes. The most potent flavonoid obtained in this study was 4,2′-dihydroxy-4′,5′,6′-trimethoxychalcone, which caused 75% and 90% inhibition of cellular lipid accumulation at 30 and 50?μmol/L, respectively. Both kaempferide and 4,2′-dihydroxy-4′,5′,6′-trimethoxychalcone were major constituents in the ethyl acetate extract of this plant.
Conclusion
C. odorata leaves contained several flavonoids with anti-adipogenic effects against lipid accumulation in 3T3-L1 adipocytes. The plant, normally considered a useless weed, may actually provide an abundant source of biologically active flavonoids.