Mahanine and 8-hydroxymahanimbine: Pancreatic lipase inhibitors with anti-hyperlipidemic effects from Clausena cambodiana leaves

This study investigated anti-pancreatic lipase compounds from Clausena cambodiana leaves and their anti-hyperlipidemic effects in a rat model. Through bioassay-guided isolation, two alkaloids with pancreatic lipase inhibitory activity were obtained. Using 1D and 2D NMR spectroscopy, their chemical structures were determined to be mahanine and 8-hydroxymahanimbine, which were corroborated by comparison with published data. These substances showed IC₅₀ values against pancreatic lipase of 25.66 and 48.69 µg/mL, respectively. The ethanol extract contains mahanine at concentrations between 35% and 38% w/w and 8-hydroxymahanimbine at levels between 9% and 11% w/w, according to HPLC examination. The lipid-lowering potential of a standardized C. cambodiana leaf extract (CE), which contains quantifiable levels of both alkaloids, was evaluated in Wistar rats with hyperlipidemia triggered by a high-fat diet (HFD). Daily monitoring was conducted for body weight, along with food and water consumption. Changes in body weight, relative fat weight, lipid profiles, and histological evaluations of kidney and pancreatic tissues were used to assess the effectiveness of the treatment after 28 days. Furthermore, acute toxicity of CE was determined in albino Wistar rats of both sexes. The HFD group showed significant increases in body weight, triglycerides, total cholesterol, and LDL levels. In contrast, CE treatment mitigated these alterations, although it did not affect relative fat weight. CE also improved liver histology and reduced adipocyte size. There were no signs of acute toxicity at a maximum dose (2000 mg/kg). These results imply that CE might have therapeutic value in the treatment of hyperlipidemia.