Fermentation-derived dihydroferulic acid from Cordyceps militaris binds AKT1 to protect intestinal epithelial health

IF 5.9 1区农林科学 Q1 FOOD SCIENCE & TECHNOLOGY

Food Bioscience Pub Date : 2025-09-24 DOI:10.1016/j.fbio.2025.107655

Rong Huang , Jixing Gao , Zelin Wang , Jie Cai , Zhenjun Zhu , Qingping Wu , Juan Wang , Fen Zhang , Yu Ding

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Abstract

Disruption of the intestinal epithelial barrier is a pivotal event of inflammatory bowel disease (IBD); however, effective therapeutic strategies to restore this barrier integrity remain elusive. In this study, we demonstrate that Cordyceps militaris (CM) modulates the gut microbiota by increasing the abundance of Megamonas and decreasing the Escherichia-Shigella genera, thereby promoting a microbiota profile conducive to gut health. Additionally, dihydroferulic acid (DHFA) was identified as a key microbiota metabolite derived from CM. Computational analyses revealed that protein kinase B (AKT1) serves as a direct binding target for DHFA in IBD. Cell-based experiments further demonstrated that pretreatment with DHFA reduces reactive oxygen species (ROS) levels and prevents AKT1 dysregulation, thus reducing hydrogen peroxide (H₂O₂)-induced apoptosis in intestinal epithelial cells, ultimately alleviating epithelial injury. These results delineate the anti-inflammatory effects of CM and shed light on the development of strategies for the prevention and treatment of IBD.

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蛹虫草发酵衍生的二氢阿魏酸结合AKT1保护肠上皮健康

肠上皮屏障的破坏是炎症性肠病（IBD）的关键事件；然而，恢复这种屏障完整性的有效治疗策略仍然难以捉摸。在这项研究中，我们证明了蛹虫草（CM）通过增加大单胞菌的丰度和减少埃希氏菌-志贺氏菌属来调节肠道微生物群，从而促进有利于肠道健康的微生物群。此外，二氢阿魏酸（DHFA）被确定为来自CM的关键微生物代谢产物。计算分析显示，蛋白激酶B （AKT1）是IBD中DHFA的直接结合靶点。基于细胞的实验进一步证明，DHFA预处理可降低活性氧（ROS）水平，防止AKT1失调，从而减少过氧化氢（H2O2）诱导的肠上皮细胞凋亡，最终减轻上皮损伤。这些结果描述了CM的抗炎作用，并为IBD的预防和治疗策略的发展提供了线索。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Food Bioscience Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

6.40

自引率

5.80%

发文量

671

审稿时长

27 days

期刊介绍： Food Bioscience is a peer-reviewed journal that aims to provide a forum for recent developments in the field of bio-related food research. The journal focuses on both fundamental and applied research worldwide, with special attention to ethnic and cultural aspects of food bioresearch.