Mechanistic insights into the anti-obesity actions of coumarins: Therapeutic potential and future directions

Abstract

Obesity is a complex and chronic metabolic disorder characterized by excessive fat accumulation, leading to severe health complications such as diabetes, cardiovascular diseases, and metabolic syndromes. Traditional drug and lifestyle changes can help, but they have problems like side effects and don't work for a long time, so people need to look for other ways to treat their conditions. Coumarins, a diverse class of naturally occurring polyphenolic compounds, have garnered significant attention for their potential anti-obesity effects. This review systematically explores the mechanistic pathways of coumarins—including their modulation of lipid metabolism, glucose homeostasis, thermogenic activity, inflammation, and adipogenic signaling—highlighting their multifaceted role in combating obesity. Preclinical studies show that coumarins stop adipocytes from differentiating, speed up lipolysis, and manage key metabolic pathways involving adiponectin, AMPK, and PPARγ. New evidence also suggests that coumarins change the composition of the gut microbiota, which adds to their ability to handle obesity. However, clinical evidence remains limited, with only a few studies investigating their efficacy in human populations. Safety considerations, including potential hepatotoxicity and anticoagulant effects, also necessitate careful evaluation. Future research should focus on optimizing coumarin derivatives, elucidating their precise mechanisms, and conducting large-scale clinical trials to establish their therapeutic potential. This review shows that coumarins have a lot of potential as natural weight loss aids, but more research is needed before these results can be used in patients.