Swertianlarin, isolated from Swertia mussotii Franch, increases detoxification enzymes and efflux transporters expression in rats.
Swertianlarin, isolated from Swertia mussotii Franch and Enicostemma axillare, has hepatoprotective effects against cholestasis in rat models of hepatotoxicity. However, the underlying molecular mechanism is not clear. We then treated rats with swertianlarin for 7 d and then measured serum liver injury markers, lipids, and bile salts, as well as the expression of bile acid synthesis and detoxification enzymes (e.g. Cyp7a1 and Cyp3a), membrane influx and efflux transporters (e.g. Ntcp and Mrp3), nuclear receptors (e.g. Pxr and Fxr/Shp) and transcriptional factors (e.g. Nrf2 and Hnf3β) in the liver. We found a significant induction of the expression of the basolateral efflux transporters Mrp3 and Mrp4 and canalicular transporter Mdr1 in rats treated with swertianlarin, compared with the controls (1.9-fold and 2.2-fold, P < 0.005, and 3.4-fold, P < 0.05, respectively). The expression of detoxification enzymes Cyp3a, Ugt2b, Sult2a1 and Gsta1 in rats treated with swertianlarin was significantly higher than that in controls (3.7-fold, 2.8-fold, 2.1-fold, and 1.7-fold, respectively, all P < 0.05). Expression of the synthetic enzyme, Cyp8b1, was higher in rats treated with swertianlarin than that in controls (1.8-fold at mRNA level and 3.4-flod at protein level, P < 0.05). Elevated serum levels of the conjugated bile acids, taurocholic acid and taurodeoxycholic acid, and a reduction in levels of serum ALP, unconjugated bile acid αMCA, and TG were observed (all P < 0.05). In conclusion, swertianlarin significantly up-regulates hepatic bile acid detoxification enzymes and efflux transporters in rats, which can increase the water solubility of hydrophobic bile acids and elimination of conjugated bile acids.
['Feng|Xin-Chan|XC|', 'Du|Xiaohuang|X|', 'Chen|Sheng|S|', 'Yue|Dongmei|D|', 'Cheng|Ying|Y|', 'Zhang|Liangjun|L|', 'Gao|Yu|Y|', 'Li|Shaoxue|S|', 'Chen|Lei|L|', 'Peng|Zhihong|Z|', 'Yang|Yong|Y|', 'Luo|Weizao|W|', 'Wang|Rongquan|R|', 'Chen|Wensheng|W|', 'Chai|Jin|J|']
D000818:Animals D001647:Bile Acids and Salts D015153:Blotting, Western D002779:Cholestasis D002851:Chromatography, High Pressure Liquid D004195:Disease Models, Animal D005455:Fluorescent Antibody Technique D008099:Liver D008297:Male D026901:Membrane Transport Proteins D010936:Plant Extracts D051381:Rats D017207:Rats, Sprague-Dawley D060888:Real-Time Polymerase Chain Reaction D020133:Reverse Transcriptase Polymerase Chain Reaction D029967:Swertia D015854:Up-Regulation
Swertianlarin hepatic efflux transporters nuclear receptors and transcriptional factors synthetic and detoxification enzymes