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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.

ABSTRACT: 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.

SUBMITTER: Luo S

PROVIDER: S-EPMC7215673 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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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.

Luo Shiqi S Gill Harsharn H Feltis Bryce B Hung Andrew A Nguyen Linh Toan LT Lenon George Binh GB

International journal of molecular sciences 20200419 8

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 s ...[more]

PMID: 32325890

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Project description:AimsObesity 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 methodsFluorometric 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 findingsThe 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.ConclusionOur 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.

Project description:An-Gong-Niu-Huang-Wan (AGNHW) is a well-known formula for treating cerebrovascular diseases, with roles including clearing away heat, detoxification, and wake-up consciousness. In recent years, AGNHW has been commonly used for the treatment of ischemic stroke, but the mechanism by which AGNHW relieves stroke has not been clearly elucidated. In the current study, we developed a multiple systems pharmacology-based framework to identify the potential antistroke ingredients in AGNHW and explore the underlying mechanisms of action (MOA) of AGNHW against stroke from a holistic perspective. Specifically, we performed a network-based method to identify the potential antistroke ingredients in AGNHW by integrating the drug-target network and stroke-associated genes. Furthermore, the oxygen-glucose deprivation/reoxygenation (OGD/R) model was used to validate the anti-inflammatory effects of the key ingredients by determining the levels of inflammatory cytokines, including interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. The antiapoptotic effects of the key ingredients were also confirmed in vitro. Integrated pathway analysis of AGNHW revealed that it might regulate three biological signaling pathways, including IL-17, TNF, and PI3K-AKT, to play a protective role in stroke. Moreover, 30 key antistroke ingredients in AGNHW were identified via network-based in silico prediction and were confirmed to have known neuroprotective effects. After drug-like property evaluation and pharmacological validation in vitro, scutellarein (SCU) and caprylic acid (CA) were selected for further antistroke investigation. Finally, systems pharmacology-based analysis of CA and SCU indicated that they might exert antistroke effects via the apoptotic signaling pathway and inflammatory response, which was further validated in an in vitro stroke model. Overall, the current study proposes an integrative systems pharmacology approach to identify antistroke ingredients and demonstrate the underlying pharmacological MOA of AGNHW in stroke, which provides an alternative strategy to investigate novel traditional Chinese medicine formulas for complex diseases.

Project description:IntroductionAtopic dermatitis is a chronic, inflammatory skin rash that greatly affects quality of life. The current therapies are inadequate in managing atopic dermatitis and often have associated adverse effects or drug tolerance development. Chinese medicine is expected to have promising prospects in the management of atopic dermatitis and recent studies have shown encouraging results. This study aims to evaluate the efficacy and safety of a newly formulated Chinese herbal formula, RMIT Chinese Medicine-106 (RCM-106), in the management of moderate-to-severe atopic dermatitis in children aged 6-18 years.MethodsThe study is a randomised, double-blind, placebo-controlled, parallel-armed clinical trial. Participant, investigator and assessors will remain blinded to the treatment assignment until after the study has been completed. After a 2-week run-in period, 90 participants will be randomised, using block randomised sequences generated by computer, to receive either RCM-106 or matching placebo capsules, twice daily, for a treatment period of 8 weeks and followed up for 4 weeks. Primary outcome measures include the evaluation of disease severity and extent using two validated scoring instruments-Scoring Atopic Dermatitis (SCORAD) and Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD). Secondary outcome measures include the evaluation of quality of life using the Children's Dermatology Life Quality Index (CDLQI); occurrence of adverse events and total usage of other therapies as recorded in the participants' daily diary and laboratory studies which include eosinophil count, total IgE, full blood count and liver and kidney function tests. Intention-to-treat analysis will be applied to all data analyses.Ethics and disseminationThis trial has received human ethics approval from the Human Research Ethics Committee (HREC) of RMIT University (Project number 15/12). The study findings will be published in peer-reviewed journals and presented at the national and international conferences.Trial registrationAustralia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612001181897. TGA CTN Scheme: Trial number 2012/0713; Protocol number 15/12.

Dataset Information

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.

Publications

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.

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