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烟草甘氨酸提取物通过NF-κB、JNK和Nrf2信号通路减轻炎症性肠病。

Glycine tabacina extract alleviates inflammatory bowel disease via NF-κB, JNK and Nrf2 signaling pathways.

作者信息

Liang Yongkai, Miao Zhimin, Chen Junming, Tan Lihua, Zhao Yuxin, Cui Xiaobing, Zhong Jinmiao, Zhong Ruting, Yue Wendi, Qiu Boyang, Yu Hua, He Chengwei

机构信息

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, 999078, China.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, 999078, China; Department of Pharmaceutical Science, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, 999078, China.

出版信息

J Ethnopharmacol. 2025 May 12;347:119744. doi: 10.1016/j.jep.2025.119744. Epub 2025 Apr 6.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the colon, often triggered by unhealthy diets, infections, and dysregulated immune responses. Current treatments for IBD are limited by relapse, drug resistance, side effects, and high costs. Glycine tabacina (Labill.) Benth, a legume native to southeastern China, has traditionally been used for its medicinal properties in treating rheumatoid arthritis, nephritis, and osteoporosis. However, its effects on IBD remain unexplored.

AIM OF THE STUDY

This study aimed to investigate the anti-colitis effects and underlying mechanisms of Glycine tabacina ethanol extract (GTE) using in vitro and in vivo models.

MATERIALS AND METHODS

The chemical components of GTE were identified using high-performance liquid chromatography (HPLC). The effects of GTE on lipopolysaccharide (LPS)-induced inflammation and oxidative stress were assessed in Caco-2 cells. Dextran sulfate sodium (DSS)-induced colitis in mice was used to evaluate GTE's therapeutic potential. ELISA, RT-qPCR, immunofluorescence, and immunoblotting were performed to measure gene expression and signaling pathway activity. Histological analysis of colon tissues was conducted using H&E staining.

RESULTS

GTE significantly reduced LPS-induced inflammation and oxidative stress in Caco-2 cells and alleviated DSS-induced colitis in mice. Mechanistically, GTE decreased pro-inflammatory cytokines, matrix metalloproteinases (MMPs), and reactive oxygen species (ROS), while improving intestinal barrier integrity. Furthermore, GTE suppressed the NF-κB and MAPK/JNK pathways while activating the Nrf2 pathway. These results suggest that GTE may serve as a promising therapeutic agent for IBD by modulating key inflammatory and oxidative stress pathways.

CONCLUSIONS

The anti-inflammatory and antioxidant properties of GTE mitigated intestinal epithelial cell damage by preserving tight junction proteins and maintaining intestinal barrier integrity. Given its high efficacy and favorable safety profile, GTE represents a promising therapeutic candidate for managing chronic and refractory inflammatory disorders such as IBD.

摘要

民族药理学相关性

炎症性肠病(IBD)是结肠的慢性炎症性疾病,通常由不健康饮食、感染和免疫反应失调引发。IBD的现有治疗方法受到复发、耐药性、副作用和高成本的限制。烟豆(Glycine tabacina (Labill.) Benth)是一种原产于中国东南部的豆科植物,传统上因其药用特性而被用于治疗类风湿性关节炎、肾炎和骨质疏松症。然而,其对IBD的影响尚未得到研究。

研究目的

本研究旨在使用体外和体内模型研究烟豆乙醇提取物(GTE)的抗结肠炎作用及其潜在机制。

材料与方法

使用高效液相色谱(HPLC)鉴定GTE的化学成分。在Caco-2细胞中评估GTE对脂多糖(LPS)诱导的炎症和氧化应激的影响。使用葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎来评估GTE的治疗潜力。进行酶联免疫吸附测定(ELISA)、逆转录定量聚合酶链反应(RT-qPCR)、免疫荧光和免疫印迹以测量基因表达和信号通路活性。使用苏木精-伊红(H&E)染色对结肠组织进行组织学分析。

结果

GTE显著降低了Caco-2细胞中LPS诱导的炎症和氧化应激,并减轻了DSS诱导的小鼠结肠炎。从机制上讲,GTE减少了促炎细胞因子、基质金属蛋白酶(MMP)和活性氧(ROS),同时改善了肠道屏障完整性。此外,GTE抑制了核因子κB(NF-κB)和丝裂原活化蛋白激酶/应激活化蛋白激酶(MAPK/JNK)通路,同时激活了核因子E2相关因子2(Nrf2)通路。这些结果表明,GTE可能通过调节关键的炎症和氧化应激通路而成为IBD的一种有前景的治疗药物。

结论

GTE的抗炎和抗氧化特性通过保留紧密连接蛋白和维持肠道屏障完整性减轻了肠上皮细胞损伤。鉴于其高效性和良好的安全性,GTE是治疗IBD等慢性和难治性炎症性疾病的一种有前景的候选药物。

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