title: Swertianlarin, isolated from Swertia mussotii Franch, increases detoxification enzymes and efflux transporters expression in rats.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Third Military Medical University Chongqing 400038.
authors.forename: Xin-Chan
authors.initials: XC
authors.lastname: Feng
authors.affiliation: Department of Traditional Chinese Medicine, Third Military Medical University Chongqing 400038.
authors.forename: Xiaohuang
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Pediatrics, Southwest Hospital, Third Military Medical University Chongqing 400038.
authors.forename: Sheng
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Employee Health, Third Military Medical University Chongqing 400038.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Yue
authors.affiliation: Department of Gastroenterology, Third Military Medical University Chongqing 400038.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, Third Military Medical University Chongqing 400038.
authors.forename: Liangjun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Third Military Medical University Chongqing 400038.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology, Third Military Medical University Chongqing 400038.
authors.forename: Shaoxue
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Third Military Medical University Chongqing 400038.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Third Military Medical University Chongqing 400038.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Chongqing Academy of Chinese Material Medical Chongqing 400065, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Chongqing Academy of Chinese Material Medical Chongqing 400065, P. R. China.
authors.forename: Weizao
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology, Third Military Medical University Chongqing 400038.
authors.forename: Rongquan
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Third Military Medical University Chongqing 400038.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Third Military Medical University Chongqing 400038.
authors.forename: Jin
authors.initials: J
authors.lastname: Chai
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D015153:Blotting, Western; D002779:Cholestasis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029967:Swertia / Q000737:chemistry*; D015854:Up-Regulation
chemical_list: D001647:Bile Acids and Salts; D026901:Membrane Transport Proteins; D010936:Plant Extracts
keywords: Swertianlarin; hepatic efflux transporters; nuclear receptors and transcriptional factors; synthetic and detoxification enzymes