Estrogens, and particularly
glucuronides such as ethinylestradiol (EE), have been shown to cause
cholestasis in animal studies, by reducing
bile acid uptake by hepatocytes. The aim of the present article is to investigate anticholestatic activity of the ethanolic extract of the aerial parts of Jasonia montana against liver
cholestasis induced by EE in adult female rats in an attempt to understand its mechanism of action, which may pave the way for possible therapeutic applications. Subcutaneous administration of 100 μg/kg b.w. ethinylestradiol to rats induced hepatocellular
cholestasis with a significant decrease in serum
cholesterol,
bile acids and
bilirubin levels as well as in hepatic
superoxide dismutase (SOD),
glutathione peroxidase (GPx),
glutathione reductase (GR) activities and hepatic total,
protein-bound and non-
protein sulfhydryl groups. Also, treatment with EE produced significant increase in serum Pi-
glutathione-s-transferase (Pi-GST),
gamma glutamyl transpeptidase (γ-GT) and alpha-
glutathione-s-transferase (α-GST) activities as well as serum
nitric oxide (NO) and
tumor necrosis factor alpha (TNF-α) level and hepatic
malondialdehyde (MDA) level as compare to control group.
Oral administration of the aerial parts of ethanolic extract at a concentration of 150 mg/kg b.w. daily to rats treated with EE for 15 days showed a significant protection against-induced decrease in serum
cholesterol,
bile acids and
bilirubin levels. The treatment also resulted in a significant increase in hepatic SOD, GPx and GR activities as well as hepatic total,
protein-bound and non-
protein sulfhydryl groups. In addition, the extract could inhibit serum Pi-GST, γ-GT and α-GST activities as well as reduce serum TNF-α, NO and hepatic MDA as compare to ethinylestradiol treated rats. High content of
flavonoids and phenolic compounds was found in ethanolic extract, which may be responsible for
free radical activity. The results clearly suggest that the aerial parts of J. montana extract may effectively normalize the impaired
antioxidant status in ethinylestradiol (EE)-cholestatic model. Thus the extract may have a therapeutic value in
drug-induced biliary
cholestasis as well as in hormonal
therapy.