Anti-pancreatic lipase and anti-adipogenic effects of 5,7,3′,4′,5′-pentamethoxy and 6,2′,4′-trimethoxy flavone - An in vitro study

• Main Authors: Bilal, Ahmad, Emily P., Friar, Emerald, Taylor, Muhammad Sufyan, Vohra, Christopher J., Serpell, Michelle D., Garrett, Jason Siau Ee, Loo, Isabel Lim, Fong, Eng Hwa, Wong
• Format: Article
• Language: English
• Published: Elsevier Science Direct 2023
• Subjects: QD Chemistry; RM Therapeutics. Pharmacology
• Online Access: http://ir.unimas.my/id/eprint/41472/3/Anti-pancreatic%20-%20Copy.pdf; http://ir.unimas.my/id/eprint/41472/; https://www.sciencedirect.com/journal/european-journal-of-pharmacology; https://doi.org/10.1016/j.ejphar.2022.175445

In this study, the anti-obesity effects of 5,7,3′,4′,5′ -pentamethoxyflavone (PMF) and 6,2′,4′-trimethoxyflavone (TMF) were evaluated through two distinct mechanisms of action: inhibition of crude porcine pancreatic lipase(PL), and inhibition of adipogenesis in 3T3-L1 pre-adipocytes. Both flavones show dose dependent, competitive inhibition of PL activity. Molecular docking studies revealed binding of the flavones to the active site of PL. In 3T3-L1 adipocytes, both flavones reduced the accumulation of lipids and triglycerides. PMF and TMF also lowered the expression of adipogenic and lipogenic genes. They both reduced the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ), CCAAT/enhancer-binding protein α and β (C/EBP α and β), sterol regulatory element-binding protein 1 (SREBF 1), fatty acid synthase (FASN), adipocyte binding protein 2(aP2), and leptin gene. In addition, these flavones enhanced adiponectin mRNA expression, increased lipolysis and enhanced the expression of lipolytic genes: adipose triglycerides lipase (ATGL), hormone sensitive lipase (HSL) and monoglycerides lipase (MAGL) in mature 3T3-L1 adipocytes. Overall, PMF was seen to be a more potent inhibitor of both PL activity and adipogenesis versus TMF. These results suggest that PMF and TMF possess anti-obesity activities and can be further evaluated for their anti-obesity effects.