Discovery of ganodecalone A, from Ganoderma calidophilum for the treatment of acute gastric ulcers by binding to ALOX5 via the MAPK/NF-κB/iNOS signaling

Yu Liu; Weikang Li; Li Yang; Zhao Tong; Zhen Wang; Youxing Zhao; Duqiang Luo

doi:10.1016/j.jep.2025.120082

Discovery of ganodecalone A, from Ganoderma calidophilum for the treatment of acute gastric ulcers by binding to ALOX5 via the MAPK/NF-κB/iNOS signaling

J Ethnopharmacol. 2025 Jun 5:351:120082. doi: 10.1016/j.jep.2025.120082. Online ahead of print.

Authors

Yu Liu¹, Weikang Li¹, Li Yang², Zhao Tong¹, Zhen Wang³, Youxing Zhao⁴, Duqiang Luo⁵

Affiliations

¹ College of Life Sciences, Institute of Life Science and Green Development and Hebei Innovation Center for Bioengineering and Biotechnology, Hebei University, Baoding, 071002, China.
² Research and Development of Natural Product from Li Folk Medicine & National Key Laboratory for Tropical Crop Breeding, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agriculture Sciences, Haikou, 571101, China.
³ Hebei Key Laboratory of Medical Data Science, School of Medicine, Hebei University of Engineering, Handan, Hebei Province, 056038, China. Electronic address: wangzhen@hebeu.edu.cn.
⁴ Research and Development of Natural Product from Li Folk Medicine & National Key Laboratory for Tropical Crop Breeding, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agriculture Sciences, Haikou, 571101, China. Electronic address: zhaoyouxing@itbb.org.cn.
⁵ College of Life Sciences, Institute of Life Science and Green Development and Hebei Innovation Center for Bioengineering and Biotechnology, Hebei University, Baoding, 071002, China. Electronic address: duqiangluo@hbu.edu.cn.

PMID: 40482864
DOI: 10.1016/j.jep.2025.120082

Abstract

Ethnopharmacological relevance: "Li medicine" Ganoderma calidophilum is a rare and unique medicinal fungus native to Hainan, China, traditionally used to relieve stomach pain and treat gastric diseases. However, its medicinal applications lack scientific validation despite its prominent role in ethnomedicine.

Aim of the study: This study aimed to evaluate the therapeutic potential of G. calidophilum extract against gastric ulcer (GU), isolate its main bioactive compound (GDA), and elucidate the underlying mechanisms of action.

Materials and methods: In vivo, acute gastric mucosal-injured mice were observed for mucosal symptoms, and levels of IL-6, TNF-α, SOD, and MDA were measured. In vitro, ethanol-damaged GES-1 cells were used to test the effects of G. calidophilum extract and GDA. 28 compounds were isolated from the extract, and network pharmacology and molecular docking studied GDA influence on ALOX5 and NF-κB.

Results: The extract improved mouse symptoms regulated inflammatory and oxidative stress markers. GDA, the key anti-inflammatory compound, repaired cell damage, reduced inflammation and oxidative stress. Network and docking results showed GDA inhibited early-stage inflammation.

Conclusions: G. calidophilum extract exhibits potent anti-GU activity, primarily attributed to GDA, which alleviates gastric mucosal inflammation by binding to ALOX5 and modulating MAPK/NF-κB/iNOS signaling and lipid peroxidation. These findings validate its traditional use and provide a mechanistic basis for its therapeutic application in acute GU.

Keywords: Ganodecalone A; Ganoderma calidophilum; Gastric ulcer; Inflammation; MAPK/NF-κB/iNOS signalling; Oxidative stress.