Recent advances in saponin-lipase-microbiota triad effect on obesity management, a comprehensive review

In the continuous effort to unravel the role of saponins on human health and nutrition, with a focus on its inhibitory effect on lipase enzyme as a target for obesity management, this review covers a compilation of recent literature on saponin - lipase interaction in addition to an elaboration on the gut microbiota involvement in saponins metabolism and consequently their anti-obesity activity. In silico non-covalent and covalent molecular docking was performed on selected saponins with reported high and low inhibitory potency as well as their corresponding aglycons to rationalize their inhibitory effect on lipase enzyme. We believe these findings may aid in the understanding of the mechanism of action of these intriguing compounds found in several edible plants. Through investigating their binding affinities and interaction modes, we aim to reveal the most promising saponins/sapogenins to encourage further exploration of the possibility of utilizing these natural compounds for obesity management. Results have revealed two lupane-type triterpene tri-glycosides namely sessiloside (21) and chiisanoside (22) to have the highest anti-lipase activity. The non-covalent docking study revealed compounds 21 and 22 form hydrogen bonds with the hydroxyl group of Ser152 and the side chain carboxylate group of Asp79 within the active site of pancreatic lipase. Additionally, the hydroxyl groups of compound 21 and the ester carbonyl group of compound 22 were found to interact with the backbone NH of Gly76 and Tyr114, respectively. The lipophilic aglycones of these compounds were also subjected to docking studies. In addition, covalent docking study confirmed that the aglycones of both compounds can react with the hydroxyl group of Ser116, forming a covalent ester bond. These interactions help us to understand how the lupane-type triterpene 21 and 22 bind to the active site of pancreatic lipase, which can guide further development of potent lipase inhibitors.