Targeted Metabolomics of Serum Acylcarnitines Evaluates Hepatoprotective Effect of Wuzhi Tablet (Schisandra sphenantheraExtract) against Acute Acetaminophen Toxicity

Author:

Bi Huichang12,Li Fei2,Krausz Kristopher W.2,Qu Aijuan2,Johnson Caroline H.23,Gonzalez Frank J.2

Affiliation:

1. School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuandong Road, University City, Guangzhou 510006, China

2. Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA

3. Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, La Jolla, CA 92037, USA

Abstract

Possible prevention and therapeutic intervention strategies to counteract acetaminophen (APAP) hepatotoxicity would be of great value. Wuzhi tablet (WZ, extract ofSchisandrae sphenanthera) possesses hepatoprotective effects against hepatitis and the hepatic dysfunction induced by various chemical hepatotoxins. In this study, the protective effect of WZ on APAP-induced hepatic injury was evaluated and targeted metabolomics by LC-MS-based metabolomics was used to examine whether WZ influences hepatic metabolism. The results demonstrated significant hepatoprotection of WZ against APAP-induced liver injury; pretreatment with WZ prior to APAP administration blocks the increase in serum palmitoylcarnitine and oleoylcarnitine and thus restores the APAP-impaired fatty acidβ-oxidation to normal levels. These studies further revealed a significant and prolonged upregulation of the PPARαtarget genesCpt1andAcot1by WZ mainly contributing to the maintenance of normal fatty acid metabolism and thus potentially contributing to the hepatic protection of WZ against APAP-induced hepatic toxicity. Taken together, the current study provides new insights into understanding the hepatoprotective effect of WZ against APAP-induced liver toxicity.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

Complementary and alternative medicine

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