Berberine is as effective as the anti-obesity drug Orlistat in ameliorating betel-nut induced dyslipidemia and oxidative stress in mice

Background: Berberine is a phytochemical derived from various plants and is found to be beneficial in the treatment of cardiovascular, hepatic, metabolic, renal and infectious diseases. Betel-Nut (BN) is the fruit of the tropical palm Areca catechu, and its use as a masticatory is strongly associated with dyslipidemia, Metabolic Syndrome and oxidative stress. Hypothesis: We tested the hypothesis that berberine is as effective as the standard anti-obesity drug, orlistat, in reducing dyslipidemia, oxidative stress and aberrant lipid synthesis caused by betel-nut, in a murine model treated with an Aqueous Extract of Betel Nut (AEBN). Methods: Male and female Swiss albino mice were administered AEBN at a dose of 2 mg ml−1 in drinking water ad libitum for 16 weeks following berberine (10 mg/kg b.w.) or orlistat (20 mg/kg b.w.) were co-administered orally with AEBN for 8 weeks. At treatment endpoint, control, berberine, orlistat, AEBN, AEBN+berberine and AEBN+orlistat treated mice were sacrificed and evaluated for changes in body weight, relative organ weight, liver histology, oxidative stress, lipid profile, and free fatty acid levels. Expression of total and phosphorylated proteins catalyzing lipid synthesis was evaluated by western blotting. Findings: AEBN treated mice exhibited lower body weight and relative organ weight but fatty degeneration of the liver, dyslipidemia, decreased oleic acid and increased palmitic acid in serum and increased oxidative stress. Western blotting of liver tissue revealed increased expressions of FASN and HMGCR, together with decreased levels of pAMPKα (Thr 172) and pACC (Ser 79) in comparison to age and gender matched controls, suggesting enhanced lipid synthesis. Co-administration of AEBN with berberine or orlistat restored body weight and liver histology to near normal, and reversed all the biochemical and molecular parameters investigated. Conclusion: Berberine was found to be as effective as orlistat in reducing dyslipidemia and oxidative stress, and restoring normal lipid synthesis in a murine model of betel-nut use