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- Title
Danshen ( S alvia miltiorrhiza) water extract inhibits paracetamol-induced toxicity in primary rat hepatocytes via reducing CYP2 E1 activity and oxidative stress.
- Authors
Zhou, Xuelin; Cheung, Ching Mei; Yang, Jia‐ming; Or, Penelope M.Y.; Lee, Wayne Y.W.; Yeung, John H.K.
- Abstract
Objectives This study aimed to investigate the protective effects of Danshen ( S alvia miltiorrhiza) water extract ( DSE) and its major phenolic acid components against CYP2 E1-mediated paracetamol ( APAP)-induced hepatic toxicity. Methods The protection and underlying mechanisms were detected in CYP2 E1 overexpression primary rat hepatocytes by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ( MTT) assay, alamar blue assay, CYP2 E1 inhibition assay and glutathione assay. Key findings After APAP treatment, DSE (0.06-1 mg/ml) significantly increased cell viability in MTT assay. Two major components danshensu (8.2-130.5 μ m) and salvianolic acid B (Sal B; 3.3-53.5 μ m) mainly contributed to this protection, but rosmarinic acid, protocatechuic aldehyde and Sal A did not. Alamar blue assay showed that DSE, danshensu and Sal B maintained mitochondrial metabolic activity. DSE inhibited CYP2 E1 (Ki = 1.46 mg/ml) in a mixed mode in rat liver microsomes in vitro; DSE decreased APAP-induced total glutathione depletion and preserved redox status ( GSH/ GSSG ratio) in hepatocytes. Danshensu and Sal B did not inhibit CYP2 E1 or decrease total glutathione depletion, but preserved redox status. Conclusions DSE protected hepatocytes against APAP-induced injury via maintenance of mitochondrial metabolic activity, CYP2 E1 inhibition, reduction of total glutathione depletion and preservation of redox status. Danshensu and Sal B were mainly responsible for this protection.
- Subjects
LAMIACEAE; PLANT extracts; ACETAMINOPHEN; LIVER cells; OXIDATIVE stress; LABORATORY rats
- Publication
Journal of Pharmacy & Pharmacology, 2015, Vol 67, Issue 7, p980
- ISSN
0022-3573
- Publication type
Article
- DOI
10.1111/jphp.12381