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Salvianolic Acid B Protects Against Acetaminophen Hepatotoxicity by Inducing Nrf2 and Phase II Detoxification Gene Expression via Activation of the PI3K and PKC Signaling Pathways

Salvianolic Acid B Protects Against Acetaminophen Hepatotoxicity by Inducing Nrf2 and Phase II Detoxification Gene Expression via Activation of the PI3K and PKC Signaling Pathways

Musen Lin, Xiaohan Zhai, Guangzhi Wang, Xiaofeng Tian, Dongyan Gao, Lei Shi, Hang Wu, Qing Fan, Jinyong Peng, Kexin Liu, Jihong Yao

J Pharmacol Sci. 2015 Feb;127(2):203-10.

PMID: 25727958

Abstract:

Acetaminophen (APAP) is used drugs worldwide for treating pain and fever. However, APAP overdose is the principal cause of acute liver failure in Western countries. Salvianolic acid B (SalB), a major water-soluble compound extracted from Radix Salvia miltiorrhiza, has well-known antioxidant and anti-inflammatory actions. We aimed to evaluate the ability of SalB to protect against APAP-induced acute hepatotoxicity by inducing nuclear factor-erythroid-2-related factor 2 (Nrf2) expression. SalB pretreatment ameliorated acute liver injury caused by APAP, as indicated by blood aspartate transaminase levels and histological findings. Moreover, SalB pretreatment increased the expression of Nrf2, Heme oxygenase-1 (HO-1) and glutamate-l-cysteine ligase catalytic subunit (GCLC). Furthermore, the HO-1 inhibitor zinc protoporphyrin and the GCLC inhibitor buthionine sulfoximine reversed the protective effect of SalB. Additionally, siRNA-mediated depletion of Nrf2 reduced the induction of HO-1 and GCLC by SalB, and SalB pretreatment activated the phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC) signaling pathways. Both inhibitors (PI3K and PKC) blocked the protective effect of SalB against APAP-induced cell death, abolishing the SalB-induced Nrf2 activation and decreasing HO-1 and GCLC expression. These results indicated that SalB induces Nrf2, HO-1 and GCLC expression via activation of the PI3K and PKC pathways, thereby protecting against APAP-induced liver injury.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1693374-A	Acetaminophen Related Compound B		1693-37-4	Price

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