Poria cocos compounds targeting neuropeptide Y1 receptor (Y1R) for weight management: A computational ligand- and structure-based study with molecular dynamics simulations identified beta-amyrin acetate as a putative Y1R inhibitor.

Poria cocos (PC) is a medicinal herb frequently used in weight-loss clinical trials, however the mechanisms by which its compounds target orexigenic receptors including the neuropeptide Y1 receptor (Y1R) remain largely unknown. This study aimed to screen PC compounds for favourable pharmacokinetics profiles and examine their molecular mechanisms targeting Y1R. Forty-three PC compounds were systematically sought from pharmacological databases and docked with Y1R (PDB: 5ZBQ). By comparing the relative binding affinities, pharmacokinetics and toxicity profiles, we hypothesised that compounds designated PC1 3,4-Dihydroxybenzoic acid, PC8 Vanillic acid, PC40 1-(alpha-L-Ribofuranosyl)uracil, could be potential antagonists as they contact major residues Asn283 and Asp287, similar to various potent Y1R antagonists. In addition, PC21 Poricoic acid B, PC22 Poricoic acid G and PC43 16alpha,25-Dihydroxy-24-methylene-3,4-secolanosta-4(28),7,9(11)-triene-3,21-dioic acid, contacting Asn299, Asp104 and Asp200 proximal to the extracellular surface could also interfere with agonist binding by stabilising the extracellular loop (ECL) 2 of Y1R in a closed position. Owing to their selective interaction with Phe302, an important residue in binding of selective Y1R antagonists, PC12 beta-Amyrin acetate, PC26 3-Epidehydrotumulosic acid and PC27 Cerevisterol were proposed as putative antagonists. Following the consensus approach, PC12 beta-Amyrin acetate, PC26 3-Epidehydrotumulosic acid and PC27 Cerevisterol were identified as candidate compounds due to their high affinities (-12.2, -11.0 and -10.8 kcal, respectively), high drug-likeness and low toxicity profiles. Trajectory analyses and energy contributions of PC12-Y1R complex further confirmed their structural stability and favourable binding free energies, highlighting the feasibility and possible development of PC12 beta-Amyrin acetate as a future Y1R inhibitor.

The clinical evaluation of electroacupuncture combined with mindfulness meditation for overweight and obesity: study protocol for a randomized sham-controlled clinical trial.

BACKGROUND: Overweight and obesity have reached an epidemic level which impacts individual health and creates a financial burden worldwide. Evidence has shown that electroacupuncture is effective for weight loss when combined with lifestyle intervention, while mindfulness meditation can enhance the outcome of weight loss programs. This study aims to evaluate the safety and the add-on effect of electroacupuncture and mindfulness meditation for weight management in overweight and obesity. METHODS/DESIGN: This is a sham-controlled, three-armed randomized clinical trial. A total of 165 participants with BMI between 25 and 39.99 and aged between 18 and 60 who meet the inclusion and exclusion criteria will be randomized into [1] electroacupuncture plus mindfulness meditation group, [2] sham electroacupuncture plus mindfulness meditation group, and [3] electroacupuncture only group. The total duration of this study will be 22 weeks, which consists of a 2-week run-in period, a 12-week intervention period, and an 8-week follow-up period. Participants will receive 12 weekly treatments during the intervention period. Primary outcomes will include body mass index, waist and hip ratio, and body composition. Secondary outcomes will be measured by the Weight-Related Symptom Measure, Obesity and Weight Loss Quality of Life, the Power of Food Scale, and the Chinese medicine differential diagnosis questionnaire. Outcomes will be assessed at the baseline, and endpoints of the 3rd, 6th, 9th, 12th, 14th, 16th, and 20th week. DISCUSSION: This clinical trial will investigate the add-on effect of two combined interventions for weight loss treatment. The findings of this study may contribute to the development of a cost-effective and multidisciplinary weight management approach. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000964213. Registered on 07 June 2018.

The Effects and Safety of Chinese Herbal Medicine on Blood Lipid Profiles in Placebo-Controlled Weight-Loss Trials: A Systematic Review and Meta-Analysis.

This study was conducted to assess the effects and safety of Chinese herbal medicine (CHM) on blood lipids among adults with overweight or obesity. Fourteen bibliographic databases were comprehensively searched, from their respective inceptions up to April 2021, for randomised placebo-controlled weight-loss trials using CHM formulation on total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol over ≥4 weeks. Data collection, risk of bias assessment, and statistical analyses were guided by the Cochrane Handbook (v6.1). Continuous outcomes were expressed as the mean difference with 95% confidence intervals, and categorical outcomes were expressed as a risk ratio with 95% confidence intervals. All analyses were two-tailed with a statistical significance of p < 0.05. Fifteen eligible studies with 1,533 participants were included in this meta-analysis. Findings from meta-analyses indicated that CHM interventions, compared to placebo, reduced triglyceride (MD -0.21 mmol/L, 95% CI -0.41 to -0.02, I 2 = 81%) and increased HDL cholesterol (MD 0.16 mmol/L, 95% CI 0.04 to 0.27, I 2 = 94%) over a median of 12 weeks. The reduction in total cholesterol and LDL cholesterol were not statistically significant. Furthermore, the tendency of reduced triglycerides was identified among overweight participants with high baseline triglycerides. Attrition rates and frequency of adverse events were indifferent between the two groups. CHM may provide lipid-modulating benefits on triglycerides and HDL cholesterol among participants with overweight/obesity, with the tendency for significant triglyceride reduction observed among overweight participants with high baseline triglycerides. However, rigorously conducted randomised controlled trials with larger sample sizes are required to validate these findings.

Feasibility of self-administered acupressure for allergic rhinitis: a pilot randomized controlled trial and lessons learnt for future studies.

OBJECTIVES: Allergic rhinitis (AR) is an immunoglobulin (Ig)E-mediated inflammatory condition that is highly prevalent worldwide. The aim of this pilot trial was to evaluate the feasibility and safety of self-administered acupressure for AR. METHODS: A randomized, single-blind, non-specific controlled clinical trial was conducted at Royal Melbourne Institute of Technology (RMIT) University, Melbourne, Australia. Fifteen AR patients were randomized into two groups: self-administered acupressure at five specific acupressure (SA) points or five non-specific acupressure (NSA) points (1 min/point, twice a day), and treated for 4 weeks with an 8-week follow-up period. The primary outcome was the change in 7-point scale symptom severity. Secondary outcomes included the rhinoconjunctivitis quality of life questionnaire and standardized activities (RQLQs), medication usage, adverse events and participants' opinions of the blinding method. The Statistical Package for the Social Science (SPSS) version 26 was used for data analyses. RESULTS: Fourteen participants completed the study and no major adverse events were reported. No statistically significant differences between SA and NSA groups were identified in 7-point scale symptom severity scores, RQLQs or medication usage. However, participants in the SA group believed that SA was useful for AR and recommended it for self-care. The credibility of the blinding method was successful. No adverse effects were considered to be related to the intervention. CONCLUSION: Acupressure is feasible and appears to be safe for self-administration by AR sufferers. Experience from this pilot study has guided minor amendments to the protocol. A large-scale randomized controlled trial is warranted to further investigate the efficacy and safety of self-administered acupressure for the management of AR.

Chinese Herbal Medicine for Weight Management: A Systematic Review and Meta-Analyses of Randomised Controlled Trials.

Objective: This review investigated the effects and safety of Chinese herbal medicine (CHM) formulas on weight management. Methods: Eighteen databases in English, Chinese, Korean, and Japanese were searched from their inceptions to September 2019. The treatment groups included CHM formulations, and the control included placebo, Western medication (WM), and lifestyle intervention (LI), with or without cointerventions (WM and/or LI). Quality of studies was assessed using Cochrane Collaboration's risk of bias assessment tool. Body weight and body mass index (BMI) were analysed in RevMan v5.4.1 and expressed as mean differences with 95% confidence intervals (CI), while adverse events were expressed as risk ratio with 95% CI. Results: Thirty-nine RCTs were eligible for qualitative analysis, 34 of which were included in the meta-analyses. The majority of studies had a high or unclear risk of selection, performance, and detection bias. Twenty-five CHM studies involving cointerventions revealed that CHM had significant adjunct effects on body weight and BMI at the end of treatment compared to control. No serious adverse events were reported in the CHM groups. Conclusion: CHM indicates a promising adjunct to facilitate WM or lifestyle change for weight management. However, methodological barriers such as lack of allocation concealment and double-blinding may have led to challenges in data synthesis. More rigorously designed RCTs involving cointerventions are warranted.

Screening natural product extracts for potential enzyme inhibitors: protocols, and the standardisation of the usage of blanks in α-amylase, α-glucosidase and lipase assays.

BACKGROUND: Enzyme assays have widespread applications in drug discovery from plants to natural products. The appropriate use of blanks in enzyme assays is important for assay baseline-correction, and the correction of false signals associated with background matrix interferences. However, the blank-correction procedures reported in published literature are highly inconsistent. We investigated the influence of using different types of blanks on the final calculated activity/inhibition results for three enzymes of significance in diabetes and obesity; α-glucosidase, α-amylase, and lipase. This is the first study to examine how different blank-correcting methods affect enzyme assay results. Although assays targeting the above enzymes are common in the literature, there is a scarcity of detailed published protocols. Therefore, we have provided comprehensive, step-by-step protocols for α-glucosidase-, α-amylase- and lipase-inhibition assays that can be performed in 96-well format in a simple, fast, and resource-efficient manner with clear instructions for blank-correction and calculation of results. RESULTS: In the three assays analysed here, using only a buffer blank underestimated the enzyme inhibitory potential of the test sample. In the absorbance-based α-glucosidase assay, enzyme inhibition was underestimated when a sample blank was omitted for the coloured plant extracts. Similarly, in the fluorescence-based α-amylase and lipase assays, enzyme inhibition was underestimated when a substrate blank was omitted. For all three assays, method six [Raw Data - (Substrate + Sample Blank)] enabled the correction of interferences due to the buffer, sample, and substrate without double-blanking, and eliminated the need to add substrate to each sample blank. CONCLUSION: The choice of blanks and blank-correction methods contribute to the variability of assay results and the likelihood of underestimating the enzyme inhibitory potential of a test sample. This highlights the importance of standardising the use of blanks and the reporting of blank-correction procedures in published studies in order to ensure the accuracy and reproducibility of results, and avoid overlooked opportunities in drug discovery research due to inadvertent underestimation of enzyme inhibitory potential of test samples resulting from unsuitable blank-correction. Based on our assessments, we recommend method six [RD - (Su + SaB)] as a suitable method for blank-correction of raw data in enzyme assays.

How does traditional knowledge of Cassiae semen shed light on weight management? - A classical and modern literature review.

ETHNOPHARMACOLOGICAL RELEVANCE: The seed of Senna obtusifolia (L.) H. S. Irwin & Barneby (Cassiae semen, CS) also known as Jue ming zi in China, has been traditionally used for weight management by purging the liver and improving the liver functions to support digestion. In the past decades, it has been used for hepatoprotection and treatment of overweight and other metabolic disorders such as hyperlipidaemia and diabetes. AIM OF THE REVIEW: This review aimed at providing comprehensive information on the traditional usages, pharmacology, phytochemistry and toxicology of CS and critically exploring its potential usage for clinical weight management from both traditional and modern application perspectives. MATERIALS AND METHODS: In order to fully understand the properties, actions and indications of CS, two sets of Chinese classical texts were searched, namely: Zhong Hua Yi Dian (Encyclopedia of Traditional Chinese Medicine) and Zhong Guo Ben Cao Quan Shu (Complete Collection of Traditional Texts on Chinese Materia Medica). The purpose of studying these classical texts was to determine the traditional use of CS in weight management. Comprehensive searches were also performed on seven databases for publications on original randomised clinical trials (RCT), in vivo, in vitro or in silico studies related to pharmacological effects of CS. Detailed information about the phytochemistry of CS was collected from books, encyclopedia, online databases and journal literature. FINDINGS: In classical literature review, 89 classic texts provided information of properties, actions and indications of CS. In modern literature review, 44 studies were included for analysis, including 5 RCTs, 7 in vivo studies, 14 in vitro studies, 2 in silico studies and 16 studies of mixed types. Chinese classic literature has provided traditional evidence of the usage of CS for weight management. Contemporary studies have revealed that CS has weight loss effects and possesses some other pharmacological activities supporting weight management. Some chemical compounds of CS have been hypothesised to have a direct or indirect contribution to weight control. CONCLUSIONS: The relationships between chemical compounds and the corresponding weight-loss target proteins are not fully understood. Therefore, CS constituents should be further explored for the development of novel therapeutic or preventive agents for the treatment of overweight and obesity.

Screening for a Potential Therapeutic Agent from the Herbal Formula in the 4th Edition of the Chinese National Guidelines for the Initial-Stage Management of COVID-19 via Molecular Docking.

BACKGROUND: COVID-19 caused by SARS-CoV-2 infection has been spreading through many countries since the end of 2019. The 4th edition of the national guidelines for the management of COVID-19 provides an herbal formula with 9 herbs for its management. Aim of Study. We aimed to predict the mechanism of binding of SARS-CoV-2 and SARS-CoV spike glycoproteins with angiotensin-converting enzyme 2 (ACE2) to provide a molecular-level explanation of the higher pathogenicity of SARS-CoV-2 and to identify protein sites which may be targeted by therapeutic agents to disrupt virus-host interactions. Subsequently, we aimed to investigate the formula for the initial-stage management to identify a therapeutic agent with the most likely potential to become pharmaceutical candidate for the management of this disease. MATERIALS AND METHODS: GenBank and SWISS-MODEL were applied for model creation. ClusPro was used for protein-protein docking. PDBePISA was applied for identification of possible binding sites. TCMSP was employed for identification of the chemical compounds. AutoDock Vina together with PyRx was used for the prediction and evaluation of binding pose and affinity to ACE2. SwissADME and PreADME were applied to screening and prediction of the pharmacokinetic properties of the identified chemical compounds. PyMOL was used to visualise the structural models of SARS-CoV-2 and SARS-CoV spike glycoproteins complexed to ACE2 and to examine their interactions. RESULTS: SARS-CoV-2 had two chains (labelled chains B and C) which were predicted to bind with ACE2. In comparison, the SARS-CoV had only one chain (labelled chain C) predicted to bind with ACE2. The spike glycoproteins of both viruses were predicted to bind with ACE2 via position 487. Molecular docking screening and pharmacokinetic property prediction of the herbal compounds indicated that atractylenolide III (-9.1 kcal/mol) from Atractylodes lancea (Thunb.) Dc. (Cangzhu) may be a candidate therapeutic agent for initial-stage management. CONCLUSIONS: Atractylenolide III is predicted to have a strong binding affinity with ACE2 and eligible pharmacokinetic properties, anti-inflammatory effects and antiviral effects in in vitro study, and high distribution on the lungs in in vivo study.

The Effects of a Weight-Loss Herbal Formula RCM-107 and Its Eight Individual Ingredients on Glucagon-Like Peptide-1 Secretion-An In Vitro and In Silico Study.

Obesity is a multifactorial disease that can lead to other health issues. Glucagon-like peptide-1(GLP-1), as one of the satiety signal, has been linked with appetite suppression and weight loss. Due to the limitations of GLP-1 and its analogues, alternative treatments such as herbal therapies have become popular. The herbal formula RCM-107 has demonstrated its inhibitory effects on lipid and carbohydrate absorption in our previous work. However, no published data described its effects on GLP-1 secretion. Therefore, this study aimed to determine the effects of RCM-107 and its individual ingredients on GLP-1 secretion via enzyme-linked immunosorbent assay (ELISA). Furthermore, molecular docking was performed to predict the key chemical compounds that are likely to be GLP-1 receptor agonists. Gardeniae fructus, one of the ingredients in RCM-107, demonstrated significantly greater effects on inducing GLP-1 secretion than the positive control epigallocatechin gallate (EGCG). Two Gardeniae fructus ligands, 3-epioleanolic acid and crocin were predicted to bind to the active form of GLP-1 receptor at the binding pocket with residues known for the receptor activation, suggesting that they could potentially serve as receptor agonists. Overall, this study reported the effects of researched herbs on GLP-1 secretion and proposed two compounds that may be responsible for antiobesity via GLP-1 receptor activation.

Inhibitory effect of a weight-loss Chinese herbal formula RCM-107 on pancreatic α-amylase activity: Enzymatic and in silico approaches.

Reducing carbohydrates digestion by having a low glycaemic index (GI) foods has been linked to weight loss. Inhibiting related enzymes is an alternative way to decrease carbohydrate digestion. RCM-107 (Slimming Plus), an eight-herb formula that is modified from RCM-104, indicated significant weight-loss action in clinical trials. However, no published research has studied its mechanism of action on reducing carbohydrate absorption via suppressing the activities of porcine pancreatic alpha-amylase (PPA). In this paper, we used fluorescence PPA inhibition assay to investigate the inhibitory effects of RCM-107 and the individual herbs present in this herbal mixture on amylase activity. Subsequently, molecular docking predicted the key active compounds that may be responsible for the enzyme inhibition. According to our results, both the RCM-107 formula and several individual herbs displayed α-amylase inhibitory effects. Also, marginal synergistic effects of RCM-107 were detected. In addition, alisol B, (-)-epigallocatechin-3-gallate (EGCG) and plantagoside have been predicted as the key active compounds that may be responsible for the α-amylase inhibition effect of RCM-107 according to inter-residue contact analysis. Finally, Glu233, Gln63, His305, Asp300 and Tyr151 are predicted to be markers of important areas with which potential amylase inhibitors would interact. Therefore, our data has provided new knowledge on the mechanisms of action of the RCM-107 formula and its individual herbal ingredients for weight loss, in terms of decreasing carbohydrate digestion via the inhibition of pancreatic alpha-amylase.

Phytochemistry, Ethnopharmacology, Pharmacokinetics and Toxicology of Cnidium monnieri (L.) Cusson.

Cnidium monnieri (L.) Cusson (CMC) is a traditional Chinese herbal medicine that has been widely grown and used in Asia. It is also known as "She chuang zi" in China (Chinese: ), "Jashoshi" in Japan, "Sasangia" in Korea, and "Xa sang tu" in Vietnam. This study aimed to provide an up-to-date review of its phytochemistry, ethnopharmacology, pharmacokinetics, and toxicology. All available information on CMC was collected from the Encyclopedia of Traditional Chinese Medicines, PubMed, EMBASE, ScienceDirect, Scopus, Web of Science, and China Network Knowledge Infrastructure. The updated chemical structures of the compounds are those ones without chemical ID numbers or references from the previous review. A total of 429 chemical constituents have been elucidated and 56 chemical structures have been firstly identified in CMC with traceable evidence. They can be categorized as coumarins, volatile constituents, liposoluble compounds, chromones, monoterpenoid glucosides, terpenoids, glycosides, glucides, and other compounds. CMC has demonstrated impressive potential for the management of various diseases in extensive preclinical research. Since most of the studies are overly concentrated on osthole, more research is needed to investigate other chemical constituents.

Mechanisms of Action of Cassiae Semen for Weight Management: A Computational Molecular Docking Study of Serotonin Receptor 5-HT2C.

Overweight and obesity is a growing global health concern. Current management of obesity includes lifestyle intervention, bariatric surgery and medication. The serotonin receptor, 5-HT2C, is known to mediate satiety, appetite and consumption behaviour. Lorcaserin, an appetite control drug, has demonstrated efficacy in appetite control by targeting 5-HT2C but causes undesirable side effects. This study aimed to explore the potential usage of Cassiae semen (CS), a well-known traditional Chinese medicine used to treat obesity. A computational molecular docking study was performed to determine the binding mechanism of CS compounds to the 5-HT2C receptors in both active, agonist-bound and inactive, antagonist-bound conformations. By comparing binding poses and predicted relative binding affinities towards the active or inactive forms of the receptor, we hypothesise that two of the CS compounds studied may be potent agonists which may mimic the appetite suppression effects of lorcaserin: obtusifoliol and cassiaside B2. Furthermore, two ligands, beta-sitosterol and juglanin, were predicted to bind favourably to 5-HT2C outside of the known agonist binding pocket in the active receptor, suggesting that such ligands may serve as positive allosteric modulators of 5-HT2C receptor function. Overall, this study proposed several CS compounds which may be responsible for exerting anti-obesity effects via appetite suppression by 5-HT2C receptor activation.

The inhibitory effects of an eight-herb formula (RCM-107) on pancreatic lipase: enzymatic, HPTLC profiling and in silico approaches.

AIMS: Obesity is a global, public health issue that causes or exacerbates serious medical disorders. Chinese herbal therapies have become one of the most popular alternatives due to intolerances of current anti-obesity treatments. The RCM-107 formula (granule) is modified from our previous studied RCM-104 formula, which has demonstrated significant effects on weight reduction in randomized clinical trials. Up to date, there is no published scientific evidence to evaluate the effect of this formula on the weight-loss target pancreatic lipase and therefore, the aim of this study is to investigate the inhibitory effect of RCM-107 and respective individual ingredient on the pancreatic lipase activities. MAIN METHODS: Fluorometric based enzymatic assays, high-performance thin-layer chromatography (HPTLC) profiling and in silico molecular docking techniques were used to investigate the lipase inhibitory effects of the RCM-107 herbal formula and its respective individual herbs. PRINCIPLE FINDINGS: The results demonstrated the potent lipase suppressing effect of the RCM-107 formula. The majority of the ingredients from this formula also showed pancreatic lipase inhibitory activities. The presence of the known weight-loss compounds such as (-)-epigallocatechin-3-gallate (EGCG), epicatechin-3-gallate (ECG), (-)-epicatechin (EC), rutin, crocin and caffeine were identified in the RCM-107 and related single herbs using HPTLC profiling approaches. In addition, EGCG, EC and the known lipase antagonist orlistat acted on the same site. These compounds form hydrogen bonds with corresponding residues HIS152, ASP80 and GLY77, which can be considered as markers of important areas in the ligand-binding site. This may explain the details of their roles in inhibiting pancreatic lipase activities. CONCLUSION: Our data has provided new knowledge to the mechanistic properties of the RCM-107 formula and its respective individual herbal ingredients for weight loss, in terms of reducing lipid absorption via the inhibition of pancreatic lipase.

Chinese herbal formulae for the treatment of menopausal hot flushes: A systematic review and meta-analysis.

OBJECTIVES: This systematic review aimed to evaluate the therapeutic effects and safety of Chinese herbal medicine (CHM) formulae for managing menopausal hot flushes (MHF). METHODS: Seven English and Chinese databases were searched for studies from respective inceptions to February 2019. Randomized controlled trials investigating the clinical effects and safety of CHM formulae on MHF were considered for inclusion. The outcomes of subjective feelings (MHF and quality of life), objective changes (hormones and peripheral blood flow) and safety were analyzed. The most frequently prescribed formulae and herbs were summarized. RESULTS: Nineteen randomized clinical trials involving 2469 patients were included. When compared to menopausal hormone therapy, CHM had similar effects to menopausal hormone therapy on total effectiveness rate (OR 1.41, 95% CI 0.84 to 2.35) and total Kupperman index (KI) score (SMD -0.13, 95% CI -0.61 to 0.36), and could significantly reduce vasomotor symptom score (MD -0.43, 95% CI -0.55 to -0.31) and upper-body peripheral blood flow (MD -3.56, 95% CI -5.14 to -1.98 under the jaw, MD -7.10, 95% CI -11.01 to -3.19 in the fingertip). When compared to placebo, CHM could reduce MHF severity (MD -0.70, 95% CI-1.00 to -0.40) and improve total KI score (MD -12.61, 95% CI -15.21 to -10.01). However, no statistically significant changes to hormone levels were detected. Most commonly seen adverse events were mild gastrointestinal tract reactions. The most popularly studied formula was Kun Tai capsule and the most frequently prescribed herb was Bai shao (Paeoniae Radix Alba, Paeonia lactiflora Pall.). More than 50% included studies had low risks of bias in the domains of selection, performance, attrition and reporting. CONCLUSIONS: This review indicated that CHM formulae were safe to be applied in MHF females and able to improve MHF-related symptom scores as well as the peripheral blood flow. Further studies should focus on specific formulae.

Self-administered acupressure for allergic rhinitis: study protocol for a randomized, single-blind, non-specific controlled, parallel trial.

BACKGROUND: Allergic rhinitis (AR) is an IgE-mediated inflammatory disease. Current conventional therapies for AR are unsatisfactory. Acupuncture has been recommended as an optional treatment for AR patients who are interested in non-pharmacotherapy in the new clinical practice guidelines for AR. Acupressure is a sub-type of acupuncture which is non-invasive with a low risk and can be self-administered. However, the current limited evidence is compromised by the high risk of bias and heterogeneity of methodology. Therefore, rigorously designed randomized controlled trials (RCTs) are needed. This proposed RCT aims to evaluate the efficacy and safety of self-administered acupressure for the management of AR. METHODS/DESIGN: We have designed a randomized, single-blind, non-specific controlled, two-arm, parallel clinical trial involving a 2-week run-in period, a 4-week intervention period and an 8-week follow-up period. The eligible participants will be randomized into either a specific or a non-specific acupressure group. They will be required to perform self-administered acupressure on either five specific acupressure points or five non-specific acupressure points, 1 min for each point, twice a day for 4 weeks. Participants will be asked to complete self-administered questionnaires for outcome measures including a 7-point scale of symptom severity, the Rhinoconjunctivitis Quality of Life Questionnaire with Standardized Activities (RQLQs), relief medication scores, adverse events and participants' opinion of this study at the different assessment points throughout the trial period. Data will be analyzed by the chi-square or t test using Statistical Package for Social Science (SPSS) software. DISCUSSION: The findings from this study should provide scientific evidence for the efficacy and safety of self-administered acupressure for the management of AR. This study may assist the development of a non-cost, non-invasive self-management method for AR sufferers. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR), ID: ACTRN12617001106325 Registered on 28 July 2017.

Phellodendri Cortex: A Phytochemical, Pharmacological, and Pharmacokinetic Review.

BACKGROUND: Phellodendri Cortex (PC) or Huang Bai. According to the scientific database of China Plant Species and Chinese pharmacopeia 2015 edition, PC has two main species which are Phellodendron amurense Rupr (PAR) or "Guan Huang bai" in Chinese and Phellodendron chinense Schneid (PCS) or "Chuan Huang bai" in Chinese. The crude drugs of PAR and PCS are also called Phellodendri amurensis cortex (PAC) and Phellodendri chinense cortex (PCC), respectively. The medicinal part of the plant is the dried trunk bark. PC has comprehensive therapeutic effects which include anti-inflammatory, antimicrobial, anticancer, hypotensive, antiarrhythmic, antioxidant, and antipyretic agents. The exact ingredients in PC and its species are not fully summarised. AIM OF THE STUDY: This study was designed to review and evaluate the pharmacological actions of compounds and to explore the pharmacokinetic knowledge of PC and its species and to also identify the chemical compound(s) with a potential therapeutic effect on atopic dermatitis. METHODS: "Huang Bai" and its English, botanical, and pharmaceutical names were used as keywords to perform database search in Encyclopaedia of traditional Chinese Medicines, PubMed, EMBASE, MEDLINE, Science Direct, Scopus, Web of Science, and China Network Knowledge Infrastructure. The data selection criteria included all the studies that were related to the phytochemical, pharmacological, and pharmacokinetic perspectives of PC and its species or their active constituents. More importantly, the voucher number has been provided to ensure the genuine bark of PC used as the medicinal part in the studies. RESULTS: 140 compounds were summarized from PC and its species: specifically, 18 compounds from PCC, 44 compounds from PCS, 34 compounds from PAC, and 84 compounds from PAR. Obacunone and obaculactone are probably responsible for antiatopic dermatitis effect. PC and its species possess a broad spectrum of pharmacological actions including anti-inflammatory effect, antibacterial effect, antiviral effect, antitumor effect, antigout effect, antiulcer effect, neuroprotective effect, and antiatopic dermatitis effect. PC could widely distribute in plasma, liver, spleen, kidney, and brain. Berberine may be responsible for the toxic effect on the susceptible users with hemolytic disease or in the peripartum and neonatal period. CONCLUSIONS: The compounds of the crude bark of PC and its subspecies have showcased a wide range of pharmacological effects. Pharmacological efficacies of PC are supported by its diverse class of alkaloid, limonoid, phenolic acid, quinic acid, lignan, and flavonoid. Obacunone and obaculactone could be the bioactive compounds for atopic dermatitis management. PC and its subspecies are generally safe to use but extra care is required for certain conditions and group of people.

Do the Natural Chemical Compounds Interact with the Same Targets of Current Pharmacotherapy for Weight Management?-A Review.

BACKGROUND: Obesity has become a worldwide health concern. Pharmacotherapies are now being introduced because lifestyle modifications alone are insufficient for weight management. The treatment outcomes of current approved anti-obesity agents are not satisfying due to drug-related intolerances. And so natural therapies including herbal medicines are popular alternatives for weight reduction; however, there are limited studies about their mechanism of actions. METHODS: Five databases (PubMed, Scopus, Google Scholar, Science Direct, Proquest) were searched to investigate the targets and safety profiles of the current and past anti-obesity drugs that have been approved by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA) as well as the commonly used off-label agents. The targets for weight-loss natural products and their principle bioactive components have also been searched. Only articles in English were included. RESULTS: The targets for current anti-obesity single agents include pancreatic lipase, Glucagon Like Peptide-1(GLP-1) receptor, and serotonin 2C (5-HT2C) receptor. Potential targets such as amylin, pancreatic alpha amylase, leptin receptor, melanocortin receptor 4 receptor (MC4R), Peroxisome Proliferator- Activated Receptors gamma (PPAR γ), endocannabinoid 1 (CB1) receptor and Adenosine Monophosphate (AMP)-Activated Protein Kinase (AMPK) were discussed in various studies. Natural compounds have been found to interact with targets like pancreatic lipase, pancreatic alpha amylase, AMPK and PPAR γ to achieve weight reduction. CONCLUSION: Current pharmacotherapies and natural chemical compounds do act on same targets. Further investigations on the interactions between herbal compounds and the above targets are essential for the development of novel weight-loss therapies.

Acupressure for respiratory allergic diseases: a systematic review of randomised controlled trials.

OBJECTIVE: To evaluate the effects and safety of acupressure for the management of respiratory allergic diseases by systematically reviewing randomised controlled trials (RCTs). METHODS: A total of 13 electronic English and Chinese databases were searched until July 2017. Two authors extracted data and evaluated risk of bias independently. Review Manager V.5.3 was employed for data analysis. RESULTS: The literature search identified 186 papers, of which only four of met the inclusion criteria: two for allergic rhinitis (AR) and two for asthma. High and unclear risk of bias existed across all the included studies. The findings demonstrated that acupressure greater effects on the relief of nasal symptoms of AR compared with 1% ephedrine nasal drop plus thermal therapy. With either Western medicine or Chinese herbal medicine as a cointervention, one study indicated that acupressure plus salbutamol was led to a significantly greater improvement of pulmonary function for patients with asthma compared with salbutamol only. However, the remaining two studies indentified no significant differences in any outcome measures between the two groups. CONCLUSIONS: No reliable conclusions regarding the effects of acupressure on AR and asthma could be drawn by this review due to the small number of available trials with significant heterogeneity of study design and high/unclear risk of bias. Further, more rigorously designed RCTs are needed. Acupressure seems safe for symptomatic relief of AR and asthma, although larger studies are required to be able to robustly confirm its safety. TRIAL REGISTRATION NUMBER: ACTRN12617001106325; Pre-results.

Saposhnikoviae divaricata: a phytochemical, pharmacological, and pharmacokinetic review.

Saposhnikoviae divaricata (Turcz.) Schischk (SD) is a traditional Chinese herb commonly used to treat clinical conditions such as rheumatism and allergic rhinitis. This review article evaluates a collection of works on in vitro and biochemical studies of SD. The discourse on the diverse class of chromones and coumarins in SD offers an insight to the pharmacological effects of these bioactive constituents as anti-inflammatory, analgesic, immunoregulatory, antioxidative, and anti-proliferative agents. It is highlighted that there is a structural relationship between the constituents and bioactive activities, which in effect provides a valid reasoning and reaffirm the use of SD in the treatment of the pathologies in Chinese medicine.