诃子鞣酸通过改善氧化应激、炎症反应和肠道微生物群来减轻右旋糖酐硫酸钠诱导的小鼠结肠炎。
Chebulagic acid ameliorates DSS-induced colitis in mice by improving oxidative stress, inflammation and the gut microbiota.
作者信息
Zhang Song, Ren Yali, Li Min, Gao Xin, Zhang Xiao, Xu Weitian, Lu Qiping
机构信息
Postdoctoral Research Station, General Hospital of Central Theater Command Wuhan, Hubei, China.
Department of Gastroenterology, General Hospital of Central Theater Command Wuhan, Hubei, China.
出版信息
Am J Transl Res. 2025 Jun 15;17(6):4101-4118. doi: 10.62347/QWCQ2468. eCollection 2025.
OBJECTIVES
Chebulagic acid (CA), isolated from the fruits of , has a number of pharmacological activities, but its effect on ulcerative colitis (UC) has not been reported. Here, we explored the protective effect of CA against dextran sulfate sodium (DSS)-induced acute colitis and elucidated the potential mechanisms.
METHODS
The mouse model of DSS-induced acute colitis was employed to evaluate the effect of CA on UC. The expression of pro-inflammatory cytokines and tight junction proteins were evaluated by quantitative real-time PCR (qRT-PCR). Western blotting was used to explore the potential signal pathway. The gut microbiota was analyzed by 16S rDNA amplicon sequencing.
RESULTS
The data showed that CA significantly mitigated colitis severity, as manifested by the suppression of weight loss, shortening of colon, disease activity index (DAI) and histopathological score. CA increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity and reduced malondialdehyde (MDA) content in the colon of colitis mice through inhibiting the mitogen-activated protein kinase (MAPK) pathway and the activating nuclear respiratoty factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathway. Meanwhile, myeloperoxidase (MPO) activity and proinflammatory cytokines levels of the CA group were markedly decreased due to suppression of the nuclear factor kappa-B (NF-κB) signaling pathway. Moreover, CA could upregulate the expression of tight junction proteins and reduced apoptosis. Furthermore, CA remodeled the gut microbiota through suppressing the growth of harmful bacteria (, and ) and promoting the growth of beneficial bacteria (, and ).
CONCLUSIONS
This study revealed that CA treatment could ameliorate DSS-induced acute colitis mainly via reducing oxidative stress and inflammation, maintaining the integrity of the intestinal barrier and modulating diversity and abundance of gut microbiota; thus, CA may become a promising novel drug candidate for initial and maintenance therapy of UC.
目的
从诃子果实中分离得到的诃子酸（CA）具有多种药理活性，但其对溃疡性结肠炎（UC）的作用尚未见报道。在此，我们探讨了CA对葡聚糖硫酸钠（DSS）诱导的急性结肠炎的保护作用，并阐明其潜在机制。
方法
采用DSS诱导的急性结肠炎小鼠模型评估CA对UC的影响。通过定量实时PCR（qRT-PCR）评估促炎细胞因子和紧密连接蛋白的表达。采用蛋白质免疫印迹法探索潜在的信号通路。通过16S rDNA扩增子测序分析肠道微生物群。
结果
数据显示，CA显著减轻了结肠炎的严重程度，表现为体重减轻、结肠缩短、疾病活动指数（DAI）和组织病理学评分的抑制。CA通过抑制丝裂原活化蛋白激酶（MAPK）途径和激活核呼吸因子2（NRF2）/血红素加氧酶-1（HO-1）途径，增加了结肠炎小鼠结肠中超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）的活性，降低了丙二醛（MDA）含量。同时，由于核因子κB（NF-κB）信号通路的抑制，CA组的髓过氧化物酶（MPO）活性和促炎细胞因子水平显著降低。此外，CA可上调紧密连接蛋白的表达并减少细胞凋亡。此外，CA通过抑制有害细菌（如大肠杆菌、肺炎克雷伯菌和肠球菌）的生长和促进有益细菌（如双歧杆菌、乳酸杆菌和阿克曼氏菌）的生长来重塑肠道微生物群。
结论
本研究表明，CA治疗可主要通过降低氧化应激和炎症、维持肠道屏障的完整性以及调节肠道微生物群的多样性和丰度来改善DSS诱导的急性结肠炎；因此，CA可能成为UC初始和维持治疗的有前途的新型候选药物。
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