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厚朴醇提物通过调控 PI3K/AKT/NF-κB 信号通路和肠道菌群缓解远志致肠损伤。

Magnolia Officinalis Alcohol Extract Alleviates the Intestinal Injury Induced by Polygala Tenuifolia Through Regulating the PI3K/AKT/NF-κB Signaling Pathway and Intestinal Flora.

机构信息

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People's Republic of China.

出版信息

Drug Des Devel Ther. 2024 May 22;18:1695-1710. doi: 10.2147/DDDT.S461152. eCollection 2024.

Abstract

PURPOSE

Willd. (PT), a traditional Chinese medicinal plant extensively employed in managing Alzheimer's disease, exhibits notable gastrointestinal side effects as highlighted by prior investigations. In contrast, Rehd. et Wils (MO), a traditional remedy for gastrointestinal ailments, shows promising potential for ameliorating this adverse effect of PT. The objective of this study is to examine the underlying mechanism of MO in alleviating the side effects of PT.

METHODS

Hematoxylin-eosin (H&E) staining was used to observe the structural damage of zebrafish intestine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors and oxidative stress. The integrity of the intestinal tight junctions was examined using transmission electron microscope (TEM). Moreover, the expression of intestinal barrier genes and PI3K/AKT/NF-κB signaling pathway-related genes was determined through quantitative real-time PCR. The changes in intestinal microbial composition were analyzed using 16S rRNA and metagenomic techniques.

RESULTS

MO effectively ameliorated intestinal pathological damage and barrier gene expression, and significantly alleviated intestinal injury by reducing the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, and inhibiting the activation of PI3K/AKT/NF-κB pathway. Furthermore, MO could significantly increase the relative abundance of beneficial microorganisms ( and ), and reduce the relative abundance of pathogenic bacteria ( and ).

CONCLUSION

MO alleviated PT-induced intestinal injury, and its mechanism may be related to the inhibition of PI3K/AKT/NF-κB pathway activation and regulation of intestinal flora.

摘要

目的

威氏鼠尾草(PT)是一种广泛用于治疗阿尔茨海默病的中药,既往研究表明其具有明显的胃肠道副作用。而雷氏鼠尾草(MO)是一种传统的胃肠道疾病治疗药物,具有改善 PT 胃肠道副作用的潜力。本研究旨在探讨 MO 缓解 PT 胃肠道副作用的作用机制。

方法

采用苏木精-伊红(H&E)染色观察斑马鱼肠道结构损伤,酶联免疫吸附试验(ELISA)检测炎症因子和氧化应激水平,透射电子显微镜(TEM)观察肠道紧密连接的完整性。同时,通过定量实时 PCR 检测肠道屏障基因和 PI3K/AKT/NF-κB 信号通路相关基因的表达。采用 16S rRNA 和宏基因组技术分析肠道微生物组成的变化。

结果

MO 能有效改善肠道病理损伤和屏障基因表达,通过降低炎症因子 IL-1β、IL-6、TNF-α的表达,抑制 PI3K/AKT/NF-κB 通路的激活,显著减轻肠道损伤。此外,MO 还能显著增加有益微生物(和)的相对丰度,降低致病菌(和)的相对丰度。

结论

MO 缓解了 PT 引起的肠道损伤,其机制可能与抑制 PI3K/AKT/NF-κB 通路激活和调节肠道菌群有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e2c/11128259/f7c3b2d83657/DDDT-18-1695-g0001.jpg

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