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

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.