Actichinone, a new ursane triterpenoid from Actinidia chinensis roots, ameliorates NAFLD via the AMPK and NF-κB pathways

  • Eur J Pharmacol. 2025 Mar 5:990:177276. doi: 10.1016/j.ejphar.2025.177276.
Xinhua Li  1 ,  Yuanlong Zhang  1 ,  Leiqing Chen  1 ,  Xiao Xu  1 ,  Xiaohong Ma  1 ,  Shuying Lou  1 ,  Ziqiang Zou  1 ,  Chenjing Wang  1 ,  Bing Jiang  1 ,  Yunrui Cai  2 ,  Yu Qi  1 ,  Yiyuan Xi  3 ,  Min Zhao  2 ,  Pengcheng Yan  4
Affiliations
  • 1. School of Traditional Chinese Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
  • 2. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
  • 3. Clinical Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. Electronic address: [email protected].
  • 4. School of Traditional Chinese Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. Electronic address: [email protected].
PMID: 39828019 DOI: 10.1016/j.ejphar.2025.177276
Abstract

A new ursane triterpenoid, actichinone (3-oxo-2α,24-dihydroxyurs-12-en-28-oic acid, 1), was isolated from the roots of a kiwi plant Actinidia chinensis Planch, together with 18 known triterpenoids (2-19). The structure of actichinone (1) was established by extensive spectroscopic analysis. Actichinone (1) showed the most potent lipid-lowering activity in the oleic acid (OA)-induced primary mouse hepatocytes and the structure-activity relationships (SARs) were analyzed. Chemical semi-synthesis of actichinone (1) was achieved by selective oxidation of the major compound 2. Actichinone (1) exhibited significant alleviation of non-alcoholic fatty liver disease (NAFLD) in a high-fat with methionine and choline deficiency diet (HFMCD)-fed mice model, by regulating lipid accumulation and inflammatory response probably via the AMPK/SREBP-1c/PPAR-α and IKK/IκB/NF-κB signaling pathways. This study provides a promising lead compound and a new insight into the development of novel anti-NAFLD agents based on the pentacyclic triterpenoid family, and is expected to promote the high value-added comprehensive application of the A. chinensis Plants.

Keywords
AMPK; Actichinone; Actinidia chinensis roots; Anti-NAFLD effect; NF-κB.
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