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  • Title: Danshen (Salvia miltiorrhiza) water extract inhibits paracetamol-induced toxicity in primary rat hepatocytes via reducing CYP2E1 activity and oxidative stress.
    Author: Zhou X, Cheung CM, Yang JM, Or PM, Lee WY, Yeung JH.
    Journal: J Pharm Pharmacol; 2015 Jul; 67(7):980-9. PubMed ID: 25645193.
    Abstract:
    OBJECTIVES: This study aimed to investigate the protective effects of Danshen (Salvia miltiorrhiza) water extract (DSE) and its major phenolic acid components against CYP2E1-mediated paracetamol (APAP)-induced hepatic toxicity. METHODS: The protection and underlying mechanisms were detected in CYP2E1 overexpression primary rat hepatocytes by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alamar blue assay, CYP2E1 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 μm) and salvianolic acid B (Sal B; 3.3-53.5 μm) 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 CYP2E1 (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 CYP2E1 or decrease total glutathione depletion, but preserved redox status. CONCLUSIONS: DSE protected hepatocytes against APAP-induced injury via maintenance of mitochondrial metabolic activity, CYP2E1 inhibition, reduction of total glutathione depletion and preservation of redox status. Danshensu and Sal B were mainly responsible for this protection.
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