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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1444117

Celastrus orbiculatus Thunb extracts and celastrol alleviate NAFLD by preserving mitochondrial function through activating the FGF21/AMPK/PGC-1α pathway

Provisionally accepted
Junli Xue Junli Xue 1Yunchao Liu Yunchao Liu 2Boyan Liu Boyan Liu 1Xiubin Jia Xiubin Jia 2Xinsheng Fang Xinsheng Fang 3Shucun Qin Shucun Qin 1Ying Zhang Ying Zhang 2*
  • 1 The Second Affiliated Hospital of Shandong First Medical University, Tai’an, Shandong Province, China
  • 2 School of Pharmaceutical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan, Shandong, China
  • 3 College of Agronomy, Shandong Agricultural University, Taian, China

The final, formatted version of the article will be published soon.

    Objective: Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease globally, characterized by the accumulation of lipids, oxidative stress, and mitochondrial dysfunction in the liver. Celastrus orbiculatus Thunb. (COT) and its active compound celastrol (CEL) have demonstrated antioxidant and anti-inflammatory properties. Our prior research has shown the beneficial effects of COT in mitigating NAFLD induced by a high-fat diet (HFD) in guinea pigs by reducing hepatic lipid levels and inhibiting oxidative stress. This study further assessed the effects of COT on NAFLD and explored its underlying mitochondria-related mechanisms. Methods: COT extract or CEL was administered as an intervention in C57BL/6J mice fed a HFD or in HepG2 cells treated with sodium oleate. Oral glucose tolerance test, biochemical parameters including liver enzymes, blood lipid, and pro-inflammatory factors, and steatosis were evaluated. Meanwhile, mitochondrial ultrastructure and indicators related to oxidative stress were tested. Furthermore, regulators of mitochondrial function were measured using RT-qPCR and western blot. Results: The findings demonstrated significant reductions in hepatic steatosis, oxidative stress, and inflammation associated with NAFLD in both experimental models following treatment with COT extract or CEL. Additionally, improvements were observed in mitochondrial structure, ATP content, and ATPase activity. This improvement can be attributed to the significant upregulation of mRNA and protein expression levels of key regulators including FGF21, AMPK, PGC-1α, PPARγ, and SIRT3. Conclusion: These findings suggest that COT may enhance mitochondrial function by activating the FGF21/AMPK/PGC-1α signaling pathway to mitigate NAFLD, which indicated that COT has the potential to target mitochondria and serve as a novel therapeutic option for NAFLD.

    Keywords: Celastrus orbiculatus Thunb, Celastrol, NAFLD, Mitochondrial function, FGF21/AMPK/PGC-1α

    Received: 06 Jun 2024; Accepted: 22 Jul 2024.

    Copyright: © 2024 Xue, Liu, Liu, Jia, Fang, Qin and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ying Zhang, School of Pharmaceutical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan, Shandong, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.