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

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.