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Effect of a hexacyclic triterpenic acid from Euscaphis japonica on the oleic acid induced HepG2 cellular model of non-alcoholic fatty liver disease

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease associated with hepatic lipid accumulation, insulin resistance, oxidative stress, and inflammation. The CFLAR-JNK pathway plays a decisive role in the development of NAFLD. EJ1 is a new hexacyclic triterpenic acid isolated from Euscaphis japonica, a traditional herbal medicine with anti-NAFLD effect. The present study was aimed to evaluate the hepatoprotective effect of EJ1 against NAFLD in vitro and the underlying mechanisms. The biochemical parameters related to lipid accumulation, insulin resistance, oxidative stress, and inflammation in oleic acid-induced HepG2 cellular model of NAFLD were measured. In this study, EJ1 was found to significantly decrease TG and TC contents. Meanwhile, EJ1 increased hepatocellular glucose uptake and improved insulin resistance by increasing the phosphorylation levels of pIRS1, pAKT and PI3K. Furthermore, EJ1 decreased the intracellular ROS and MDA, promoted the antioxidant enzymes activity including SOD and GSH-Px. Moreover, EJ1 reduced the levels of cellular NO and mRNA of TNF-α, IL-6 and IL-8. Further investigation showed that EJ1 treatment led to up-regulation of CFLAR protein expression and down-regulation of JNK protein phosphorylation. These results revealed that EJ1 has the potential to alleviate lipid accumulation, insulin resistance, oxidative stress, and inflammatory responses in OA-treated HepG2 cellular model of NAFLD, representing a promising leading compound for NAFLD, possibly by activating the CFLAR-JNK pathway.

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Acknowledgements

This work was financially supported by the Program for Basic research project (free inquiry) of Shenzhen Science and Technology Plan (grant number JCYJ20170306171157738); National Natural Science Foundation of China (grant number 81560703); Open Foundation for National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology (grant number M20181007, M20202003); and College Student Innovation and Entrepreneurship Training Program (grant number S202010512064).

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  1. These authors contributed equally: Yu Chen, Shaojun Zhang, Yanxia Lu

Authors and Affiliations

  1. National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Key Laboratory of Biotechnology of Traditional Chinese Medicine, Hubei University, Wuhan, 430062, China

    Yu Chen, Shaojun Zhang, Yanxia Lu, Lujun Li, Yu Shi, Yueyue Lei & Xinyu Yang

  2. Gansu Herbal Medicine Planting Co., Ltd, Lanzhou, 730102, China

    Lujun Li

  3. Shenzhen Institute of Geriatrics, Shenzhen, 518020, China

    Zhengzhi Wu

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Chen, Y., Zhang, S., Lu, Y. et al. Effect of a hexacyclic triterpenic acid from Euscaphis japonica on the oleic acid induced HepG2 cellular model of non-alcoholic fatty liver disease. Med Chem Res 31, 2209–2219 (2022). https://doi.org/10.1007/s00044-022-02982-z

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