The extract of Polygala fallax Hemsl. slows the progression of diabetic nephropathy by targeting TLR4 anti-inflammation and MMP-2/9-mediated anti-fibrosis in vitro,Phytomedicine

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The extract of Polygala fallax Hemsl. slows the progression of diabetic nephropathy by targeting TLR4 anti-inflammation and MMP-2/9-mediated anti-fibrosis in vitro
Phytomedicine ( IF 6.7 ) Pub Date : 2022-06-06 , DOI: 10.1016/j.phymed.2022.154251
Minhui Wang ₁ , Xinyan Liu ₂ , Zelong Wang ₁ , Qin Xu ₁

Affiliation

Background

Polygala fallax Hemsl. is a plant that is commonly used as a folk medicine by Guangxi ethnic minorities, and it is also widely used in the clinical treatment of chronic diseases in China. The extract of P. fallax (EPF) contains key biologically active components from the roots and stems. However, the role of P. fallax or EPF in diabetic nephropathy (DN) is unclear.

Purpose

This study aimed to investigate the effects and mechanisms of EPF on high glucose (HG)-induced human glomerular mesangial cell (HMC) injury, inflammation, fibrosis, and apoptosis in vitro.

Methods

For the in vitro study, MTT and ELISA assays were performed with HG-treated HMCs, as well as MMP, Hoechst, flow cytometry, qRT-PCR, and western blot analyses. The expression of the TLR4/NF-κB pathway, along with its downstream inflammatory, apoptosis, and fibrosis factors, was measured. The expression of the TLR4/NF-κB pathway and its downstream inflammatory factors were also measured after the addition of TLR4 inhibitors.

Results

Our results suggest that EPF can reverse the hyperproliferation and apoptosis of HMCs induced by HG. In addition, the extract inhibited the increase in inflammatory factors IL-6, TNF-α, IL-1β, MCP-1, and IL-18 in cells treated with HG. The mRNA and protein expression of TLR4, MyD88, NF-κB, Col IV, FN, MMP-9, and MMP-2 were downregulated by EPF. In addition, EPF significantly reduced the loss of MMP and the upregulation of Bcl-2/Bax mRNA and protein levels after HG treatment.

Conclusion

These results demonstrated that EPF protects against diabetes-induced renal injury in vitro. EPF protected against HG-induced HMCs proliferation, apoptosis, fibrosis, and inflammation likely via inhibition of TLR4-dependent NF-κB signaling. This herbal extract may also be a novel treatment for DN.

中文翻译：

远志的提取物。通过体外靶向 TLR4 抗炎和 MMP-2/9 介导的抗纤维化减缓糖尿病肾病的进展

背景

远志谬误Hemsl。是广西少数民族常用的民间药材，在我国也广泛用于慢性病的临床治疗。P. fallax (EPF)的提取物含有来自根和茎的关键生物活性成分。然而，P. fallax或 EPF 在糖尿病肾病 (DN) 中的作用尚不清楚。

目的

本研究旨在探讨EPF在体外对高糖(HG)诱导的人肾小球系膜细胞(HMC)损伤、炎症、纤维化和细胞凋亡的影响及其机制。

方法

对于体外研究，使用 HG 处理的 HMC 以及 MMP、Hoechst、流式细胞术、qRT-PCR 和蛋白质印迹分析进行 MTT 和 ELISA 测定。测量了 TLR4/NF-κB 通路及其下游炎症、细胞凋亡和纤维化因子的表达。在添加 TLR4 抑制剂后，还测量了 TLR4/NF-κB 通路及其下游炎症因子的表达。

结果

我们的研究结果表明，EPF 可以逆转 HG 诱导的 HMC 的过度增殖和凋亡。此外，该提取物抑制了 HG 处理的细胞中炎症因子 IL-6、TNF-α、IL-1β、MCP-1 和 IL-18 的增加。TLR4、MyD88、NF-κB、Col IV、FN、MMP-9 和 MMP-2 的 mRNA 和蛋白表达被 EPF 下调。此外，EPF 显着降低了 HG 处理后 MMP 的损失和 Bcl-2/Bax mRNA 和蛋白质水平的上调。