The therapeutic potential of Laggera alata in alleviating inflammation and oxidative stress: insights into the miR-150-5p/TRIM8 axis

IF 1.1 4区 医学 Q4 TOXICOLOGY
JiangCun Wei, Sen Liang, Peng Yang, Bing Qing, JiaBao Ma, LeiMin Jiang, QingMei Deng, Wen Zhong, MingGang Wang, ZuJie Qin
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Abstract

Objective

This research was conducted to study the protective effect of Laggera alata (TPLA) on sepsis-induced liver injury (SLI).

Methods

The SLI model was established in rats by cecal ligation and puncture (CLP), and human liver THLE-3 cells were induced by LPS to establish a cellular SLI model. HE staining and TUNEL staining were performed on the liver tissue of SLI rats treated with TPLA. The effects of TPLA on THLE-3 cells were studied using CCK-8, flow cytometry, ELISA, and biochemical analysis. The functional mechanism of TPLA, miR-150-5p, and TRIM8 in SLI was studied.

Results

TPLA treatment improved SLI in CLP rats and LPS-induced human liver THLE-3 cell injury was manifested by liver tissue injury recovery and decreased apoptosis of liver cells. At the same time, inflammation and oxidative stress were also alleviated. miR-150-5p level was reduced in SLI rats and cells, while TPLA pretreatment restored miR-150-5p level. miR-150-5p inhibitors could impair the therapeutic effect of TPLA in THLE-3 cell damage. TRIM8 was a direct target of miR-150-5p, and there was a negative regulatory relationship between the miR-150-5p and TRIM8 mRNA levels. Overexpressing TRIM8 also weakened the therapeutic effect of TPLA on THLE-3 cell damage.

Conclusion

TPLA reduces TRIM8 expression by upregulating miR-150-5p, thereby reducing inflammatory response and oxidative stress, and thus significantly alleviating SLI.

Abstract Image

白花蛇舌草在缓解炎症和氧化应激方面的治疗潜力:对 miR-150-5p/TRIM8 轴的见解
方法用盲肠结扎法(CLP)建立大鼠脓毒症诱导肝损伤(SLI)模型,并用 LPS 诱导人肝 THLE-3 细胞建立细胞 SLI 模型。用 TPLA 对 SLI 大鼠的肝组织进行 HE 染色和 TUNEL 染色。利用 CCK-8、流式细胞术、ELISA 和生化分析研究了 TPLA 对 THLE-3 细胞的影响。结果TPLA治疗改善了CLP大鼠的SLI,LPS诱导的人肝脏THLE-3细胞损伤表现为肝组织损伤恢复和肝细胞凋亡减少。miR-150-5p 抑制剂会影响 TPLA 对 THLE-3 细胞损伤的治疗效果。TRIM8是miR-150-5p的直接靶标,miR-150-5p与TRIM8 mRNA水平之间存在负调控关系。结论TPLA通过上调miR-150-5p来降低TRIM8的表达,从而减轻炎症反应和氧化应激,从而显著缓解SLI。
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来源期刊
CiteScore
2.50
自引率
17.60%
发文量
114
审稿时长
6-12 weeks
期刊介绍: Molecular & Cellular Toxicology publishes original research and reviews in all areas of the complex interaction between the cell´s genome (the sum of all genes within the chromosome), chemicals in the environment, and disease. Acceptable manuscripts are the ones that deal with some topics of environmental contaminants, including those that lie in the domains of analytical chemistry, biochemistry, pharmacology and toxicology with the aspects of molecular and cellular levels. Emphasis will be placed on toxic effects observed at relevant genomics and proteomics, which have direct impact on drug development, environment health, food safety, preventive medicine, and forensic medicine. The journal is committed to rapid peer review to ensure the publication of highest quality original research and timely news and review articles.
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