Int J Biol Sci 2020; 16(5):752-765. doi:10.7150/ijbs.40612

Research Paper

Hepatoprotective Effect of Citrus aurantium L. Against APAP-induced Liver Injury by Regulating Liver Lipid Metabolism and Apoptosis

Yisong Shu1*, Dan He2*, Wen Li1, Menglei Wang1, Siyu Zhao1, Linlin Liu1, Zhiwen Cao1, Rui Liu1, Yujuan Huang1, Hui Li1, Xueqing Yang1,✉, Cheng Lu3,✉, Yuanyan Liu1,✉

1. Beijing University of Chinese Medicine, Beijing, 100029, China
2. Patent Examination Cooperation (Tianjin) Center of the Patent Office, Tianjin, 300304, China
3. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
* Yisong Shu and Dan He contributed equally to this work.

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Citation:
Shu Y, He D, Li W, Wang M, Zhao S, Liu L, Cao Z, Liu R, Huang Y, Li H, Yang X, Lu C, Liu Y. Hepatoprotective Effect of Citrus aurantium L. Against APAP-induced Liver Injury by Regulating Liver Lipid Metabolism and Apoptosis. Int J Biol Sci 2020; 16(5):752-765. doi:10.7150/ijbs.40612. Available from http://www.ijbs.com/v16p0752.htm

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Abstract

Acetaminophen (APAP) refers to a medication used to manage pain and fever symptoms, but it always causes liver injury when overdosed. Zhishi, dried young fruit of Citrus aurantium L., is a famous Citrus herbal medicine in Asian countries which is rich in dietary phenolic substances. In this study, the mechanism of Zhishi protected against APAP-induced liver injury was studied more deeply by metabolomic strategy and pharmacological study. The metabolomics results demonstrated that Zhishi can prevent the APAP-induced liver injury model by regulating liver metabolic disorders in glycerophospholipid metabolism, fatty acid biosynthesis and glycerolipid metabolism. Moreover, it is confirmed that Zhishi blocked apoptosis of APAP-induced BRL-3A cell by simultaneously regulating p53 up-regulated apoptosis regulator (PUMA), AMPK-SIRT1 and JNK1 signaling pathways. Our findings indicated that Zhishi exhibited a hepaprotective effect against APAP-induced liver necrosis by inhibiting the PUMA and reversing disorder of liver lipid metabolism which could assist in improving the clinical outcomes of chemical-induced liver injury.

Keywords: liver injury, apoptosis, hepatoprotective effect, liver metabolomics