Schisandrin B and Schisandrol B induce mouse CYP2b10 associated with CAR not PXR. (February 2020)

• Record Type: Journal Article
• Authors: Xie, Minzhu; Lin, Jiao; Kang, Jinyu; Zheng, Xiuting; Fang, Kailu; Luo, Yishuang; Liu, Aiming; Yang, Julin
• Is Part Of: Phytochemistry letters. Volume 35(2020)
• Page Start: 164
• Page End: 170
• Publication Date: 2020-02
• Subjects: SinB Schisandrin B -- SolB Schisandrol B -- CYP cytochrome P450 -- PXR pregnane X receptor -- CAR constitutive androstane receptor -- WT wild-type -- KO Pxr-null -- TCM traditional Chinese medicine -- DDI drug-drug interaction -- PCN pregnenolone-16a-carbonitrile -- PB phenobarbital sodium -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- RT-PCR real-time polymerase chain reaction -- H&E hematoxylin and eosin -- UGT glucuronosyltransferases -- Hpxr human PXR -- hCAR human CAR; Schisandrin B -- Schisandrol B -- Cytochrome P450 -- Induction -- Constitutive androstane receptor; Botanical chemistry -- Periodicals; Chimie végétale -- Périodiques; 572.205
• DOI: 10.1016/j.phytol.2019.12.001
• Languages: English
• ISSNs: 1874-3900

Abstract

Graphical abstract: Highlights: Schisandrin B and Schisandrol B strongly induce mouse CYP2B. The above inductive action is mediated by nuclear receptor CAR. Reversible and non-inflammatory edema is caused by Schisandrin B and Schisandrol B. Abstract: Schisandrin B (SinB) and Schisandrol B (SolB) are two abundant compounds with similar structures in Schisandra sphenanthera widely used for hepatic diseases in Asian countries. They are also pharmacologically active components in many other traditional Chinese medicines. However, induction features of cytochrome P450 (CYP) by SinB and SolB were not well established. The present study aimed to investigate the CYP profile induced by SinB and SolB, and the role of nuclear factors pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Wild-type (WT) and Pxr- null (KO) mice were administered SinB and SolB respectively for 5 days. CYP induction analysis was carried out and underlying mechanism was explored. CYP2b was sharply induced by SinB and SolB in WT and KO mice. CYP3a was moderately induced in WT mice, but not in KO mice. No significant induction of CYP2c or UDP glucuronosyltransferases was observed. Edema related with slight hepatomegaly was found in both WT and KO mice, which was found reversible and non-inflammatory. These data suggest SinB and SolB induced CYP3a moderately in a PXR-dependent way. In contrast, they both sharply induced CYP2b, which was supposed to be associated with nuclear factor CAR not PXR. Non-inflammatory and reversible edema contributed to hepatomegaly induced by SinB and SolB. The complicated CYP induction of SinB and SolB might cause drug-drug interactions in the clinic.