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从嗜热灵芝中发现ganodecalone A,通过丝裂原活化蛋白激酶/核因子κB/诱导型一氧化氮合酶信号通路与5-脂氧合酶结合治疗急性胃溃疡。

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.

作者信息

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

机构信息

College of Life Sciences, Institute of Life Science and Green Development and Hebei Innovation Center for Bioengineering and Biotechnology, Hebei University, Baoding, 071002, China.

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.

出版信息

J Ethnopharmacol. 2025 Jul 24;351:120082. doi: 10.1016/j.jep.2025.120082. Epub 2025 Jun 5.

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

摘要

民族药理学相关性

“黎药”喜热灵芝是一种罕见且独特的药用真菌,原产于中国海南,传统上用于缓解胃痛和治疗胃部疾病。然而,尽管它在民族医学中具有重要作用,但其药用价值缺乏科学验证。

研究目的

本研究旨在评估喜热灵芝提取物对胃溃疡(GU)的治疗潜力,分离其主要生物活性化合物(GDA),并阐明其潜在的作用机制。

材料与方法

在体内,观察急性胃黏膜损伤小鼠的黏膜症状,并检测白细胞介素-6、肿瘤坏死因子-α、超氧化物歧化酶和丙二醛的水平。在体外,使用乙醇损伤的GES-1细胞来测试喜热灵芝提取物和GDA的作用。从提取物中分离出28种化合物,并通过网络药理学和分子对接研究GDA对5-脂氧合酶(ALOX5)和核因子-κB(NF-κB)的影响。

结果

提取物改善了小鼠症状,调节了炎症和氧化应激标志物。关键抗炎化合物GDA修复了细胞损伤,减轻了炎症和氧化应激。网络和对接结果表明GDA抑制早期炎症。

结论

喜热灵芝提取物具有强大的抗胃溃疡活性,主要归因于GDA,它通过与ALOX5结合并调节丝裂原活化蛋白激酶/核因子-κB/诱导型一氧化氮合酶(MAPK/NF-κB/iNOS)信号通路和脂质过氧化来减轻胃黏膜炎症。这些发现验证了其传统用途,并为其在急性胃溃疡治疗中的应用提供了作用机制依据。

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