BACKGROUND: Lotus leaf and its extracts have been reported to exert various beneficial effects; however, their anti-obesity mechanisms remain relatively unclear. Therefore, we investigated the mechanism by which lotus leaf regulates obesity using network pharmacology, molecular docking, and animal experimentation.
METHODS: Network pharmacology was used to identify potential targets and pathways through which lotus leaf regulates obesity. Molecular docking technology was used to verify the interaction between lotus leaves and core targets of obesity. Additionally, a rat model of obesity induced using a high-fat diet was established to examine the anti-obesity effects of lotus leaf. Moreover, western blotting was performed to examine the expression levels of the target proteins and elucidate the molecular mechanisms of lotus leaf.
RESULTS: Quercetin, nuciferin, catechin, kaempferol, and isorhamnetin were identified as the main active compounds in the lotus leaves involved in obesity treatment. Network pharmacology analysis identified fibroblast growth factor (FGF) 15 and farnesoid X receptor (FXR) as core targets of lotus leaf, and the AGE-RAGE signaling pathway in diabetic complications, neuroactive ligand-receptor interactions, insulin resistance, and cancer pathways, as biomechanistic pathways by which lotus leaf ameliorates obesity. Additionally, molecular docking analysis indicated a strong binding affinity between the main active ingredients of lotus leaf and the core targets. Moreover, western blotting showed that lotus leaf significantly downregulated FGF15 and FXR protein expression in intestinal tissues.
CONCLUSIONS: Lotus leaf ameliorates obesity through several pathways, including by downregulating FGF15 and FXR, providing a novel basis for the development of natural drug therapy for obesity.
