Withaferin-A down-regulate enterohepatic circulation of bile acids: An insight from a hyperlipidemic rat model

Abstract

Hyperlipidemia is a metabolic abnormality in both young and aged populations across the world. Withaferin-A (WT) present in Withania somnifera (Indian ginseng) has been studied by many investigators for their therapeutic potentials. However, their effects on bile acid (BA) metabolism, that play a significant role in lipid homeostasis under hyperlipidemia has not been studied. This study explores the modulatory potential of WT on BA metabolism in young and aged hyperlipidemic rats. Hyperlipidemia was induced by feeding lard fat (35g/100g diet, HF) for 60 days. Withaferin-A (2.5 mg/kg diet) was fed to assess its effect on lipid metabolism and enterohepatic circulation of BA. In both models, compared to HF, WT had significantly (p < 0.05), decreased serum lipids, BA uptake, and HMG-CoA reductase activity, but increased hepatic Cyp7a1 , decreased serum BA and increased fecal BA. WT re-regulated hyperlipidemia-induced aberrations in the intestinal uptake, hepatic synthesis, and cholesterol and BA metabolism in both models. • Withaferin-A (WT) modulate dyslipidemia-induced aberrations in the enterohepatic circulation of BA in young and aged rats. • WT showed favorable interaction with the Asbt indicating potential effect on bile acids absorption. • WT lowered the lipids by down-regulating bile acid absorption and its synthesis under dyslipidemia.