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.

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.

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.