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ORIGINAL RESEARCH article

Front. Chem.

Sec. Medicinal and Pharmaceutical Chemistry

A new lanostane-type triterpene with lipid-lowering activity from Ganoderma lucidum and an additional analogue

Provisionally accepted
Hu  XueshengHu XueshengHan  LuHan LuTan  YiyingTan YiyingWu  PeitongWu PeitongLi  YajingLi YajingLiu  WanjieLiu WanjieShen  JiamingShen JiamingLi  YishanLi YishanYang  MingYang MingLi  ChunnanLi ChunnanSun  JiamingSun Jiaming*
  • Changchun University of Chinese Medicine, Changchun, China

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

Non-alcoholic fatty liver disease (NAFLD) represents a chronic liver disorder with widespread global prevalence, primarily attributed to hepatic lipid accumulation, oxidative stress, and inflammatory responses. In the realm of traditional Chinese medicine, Ganoderma lucidum is predominantly utilized for its hepatoprotective properties. The objective of this study was to isolate and identify novel bioactive compounds capable of mitigating hepatic fat accumulation. An in vitro steatosis model was established using oleic acid-induced HepG2 cells to evaluate the total triglyceride (TG) content across various components. Fractionation of the compounds was guided by the observed reduction in TG content, employing multiple chromatographic techniques to successfully isolate ten Ganoderma triterpenes. Structural elucidation was achieved through 1D and 2D NMR spectroscopy, supplemented by additional spectroscopic methods. This investigation led to the identification of two previously unreported lanostane-type triterpenes (1-2) alongside eight known analogues (3-10). Compound 1 and 2 exhibit structural distinctions from the other compounds, primarily in the substituents at positions C-3, C-7, and C-15, as well as in the spatial orientation of these substituents. In vitro experiments were conducted to assess the efficacy of various compounds in inhibiting lipid accumulation. Compound 1-5 demonstrated a significant reduction in TG levels within the OA-induced HepG2 cell model (p<0.05). In comparison to the model group, Compound 1 demonstrated a moderate lipid-lowering effect, (2.11 mmol/gprot vs 2.70 mmol/gprot, p<0.003). Conversely, Compound 2 exhibited a significantly more pronounced lipid-lowering effect, (1.27 mmol/gprot vs 2.70 mmol/gprot, p<0.0001). Furthermore, when compared with the positive control drug, the lipid-lowering efficacy of Compound 2 was significantly superior to that of Compound 1. Furthermore, the application of network pharmacology, molecular docking, and molecular dynamics simulations elucidated the mechanism of action underlying the effects of methyl ganoderenic acid A(2).

Keywords: Ganoderma lucidum, Ganoderma triterpenes, HepG2 cell, Lipid accumulation, NAFLD

Received: 16 Oct 2025; Accepted: 17 Dec 2025.

Copyright: © 2025 Xuesheng, Lu, Yiying, Peitong, Yajing, Wanjie, Jiaming, Yishan, Ming, Chunnan and Jiaming. 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: Sun Jiaming

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