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  3. Isorhapontigenin alleviates acetaminophen-induced liver injury by promoting fatty acid oxidation

Isorhapontigenin alleviates acetaminophen-induced liver injury by promoting fatty acid oxidation

  • Biochim Biophys Acta Mol Basis Dis. 2025 Feb;1871(2):167575. doi: 10.1016/j.bbadis.2024.167575.
Huiyan Zha 1,  Shuying Lv 1,  Yuming Hu 2,  Yaochen Xie 1,  Lingkun Wang 1,  Chen Yang 1,  Guilin Li 1,  Shuchen Gong 2,  Li Ping 1,  Difeng Zhu 1,  Jiajia Wang 1,  Qinjie Weng 3,  Qiaojun He 4,  Jincheng Wang 5
Affiliations

Affiliations

  • 1 Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China.
  • 2 Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China; Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
  • 3 Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China; Taizhou Institute of Zhejiang University, Taizhou, 318000, China; The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; ZJU-Xinchang Joint Innovation Center (TianMu Laboratory), Gaochuang Hi-Tech Park, Xinchang, Zhejiang 312500, China; Institute of Fundamental and Transdisciplinary Research, Zhejiang University, Hangzhou 310058, China. Electronic address: [email protected].
  • 4 Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China; ZJU-Xinchang Joint Innovation Center (TianMu Laboratory), Gaochuang Hi-Tech Park, Xinchang, Zhejiang 312500, China; Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China; Department of Pharmaceutical and Translational Toxicology, Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: [email protected].
  • 5 Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China; Taizhou Institute of Zhejiang University, Taizhou, 318000, China; Beijing Life Science Academy, Beijing, 102200, China. Electronic address: [email protected].
PMID: 39577212 DOI: 10.1016/j.bbadis.2024.167575
Abstract

Acetaminophen (APAP) is a widely used analgesic and antipyretic medicine. It is frequently employed to alleviate pain and mitigate fever-related symptoms, but it can cause liver injury or even liver failure when overdosed. Isorhapontigenin, a compound derived from Chinese herbs and grapes, has been demonstrated to exhibit antioxidant and anti-inflammatory effects. This study focused on evaluating the effect of isorhapontigenin in alleviating APAP-induced liver injury. In the study, a single intraperitoneal administration of APAP was employed to induce liver injury, and isorhapontigenin was given orally 3 days before or 1 h after APAP administration. The results revealed that isorhapontigenin significantly mitigated liver injury by effectively inhibiting APAP-induced Apoptosis, oxidative stress, and inflammation. Furthermore, transcriptomic RNA Sequencing of liver tissues indicated that isorhapontigenin probably protected against APAP-induced liver injury by promoting fatty acid oxidation. Pharmacological experiments also demonstrated that isorhapontigenin treatment led to a significant reduction in triglyceride accumulation, increased ATP levels and direct fatty acid oxidation activity, as well as enhanced expression of proteins associated with fatty acid oxidation, including PPAR-α, PGC-1α, and CPT-1A. Moreover, the protective effects of isorhapontigenin against APAP-induced liver injury were abolished by a CPT-1A inhibitor, etomoxir. Notably, we found that combining isorhapontigenin with NAC (N-acetyl-L-cysteine) resulted in a more significant alleviation of APAP-induced liver injury compared to NAC alone. In conclusion, our study indicates that isorhapontigenin is a potential therapeutic strategy that works by regulating fatty acid oxidation to alleviate APAP-induced liver injury.

Keywords

Acetaminophen; Fatty acid oxidation; Isorhapontigenin; Liver injury.

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