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紫花地丁对草酸钙诱导的肾损伤发挥保护作用 鞣花酸。

Niruri L. Exerts Protective Effects Against the Calcium Oxalate-Induced Renal Injury Ellgic Acid.

作者信息

Li Mao-Ting, Liu Lu-Lu, Zhou Qi, Huang Lin-Xi, Shi Yu-Xuan, Hou Jie-Bin, Lu Hong-Tao, Yu Bing, Chen Wei, Guo Zhi-Yong

机构信息

Changhai Hospital, Naval Medical University, Shanghai, China.

Department of Nephrology, the Second Medical Centre, Chinese PLA General Hospital, Beijing, China.

出版信息

Front Pharmacol. 2022 Jun 16;13:891788. doi: 10.3389/fphar.2022.891788. eCollection 2022.

Abstract

Urolithiasis or kidney stones is a common and frequently occurring renal disease; calcium oxalate (CaOx) crystals are responsible for 80% of urolithiasis cases. niruri L. (PN) has been used to treat urolithiasis. This study aimed to determine the potential protective effects and molecular mechanism of PN on calcium oxalate-induced renal injury. Microarray data sets were generated from the calcium oxalate-induced renal injury model of HK-2 cells and potential disease-related targets were identified. Network pharmacology was employed to identify drug-related targets of PN and construct the active ingredient-target network. Finally, the putative therapeutic targets and active ingredients of PN were verified and . A total of 20 active ingredients in PN, 2,428 drug-related targets, and 127 disease-related targets were identified. According to network pharmacology analysis, HMGCS1, SQLE, and SCD were identified as predicted therapeutic target and ellagic acid (EA) was identified as the active ingredient by molecular docking analysis. The increased expression of SQLE, SCD, and HMGCS1 due to calcium oxalate-induced renal injury in HK-2 cells was found to be significantly inhibited by EA. Immunohistochemical in mice also showed that the levels of SQLE, SCD, and HMGCS1 were remarkably restored after EA treatment. EA is the active ingredient in PN responsible for its protective effects against CaOx-induced renal injury. SQLE, SCD, and HMGCS1 are putative therapeutic targets of EA.

摘要

尿石症或肾结石是一种常见且多发的肾脏疾病;草酸钙(CaOx)晶体导致了80%的尿石症病例。肾茶已被用于治疗尿石症。本研究旨在确定肾茶对草酸钙诱导的肾损伤的潜在保护作用及分子机制。从草酸钙诱导的HK-2细胞肾损伤模型中生成微阵列数据集,并确定潜在的疾病相关靶点。采用网络药理学方法确定肾茶的药物相关靶点并构建活性成分-靶点网络。最后,对肾茶的推定治疗靶点和活性成分进行了验证。共鉴定出肾茶中的20种活性成分、2428个药物相关靶点和127个疾病相关靶点。根据网络药理学分析,通过分子对接分析确定HMGCS1、SQLE和SCD为预测治疗靶点,鞣花酸(EA)为活性成分。发现HK-2细胞中草酸钙诱导的肾损伤导致的SQLE、SCD和HMGCS1表达增加被EA显著抑制。对小鼠的免疫组织化学分析也表明,EA治疗后SQLE、SCD和HMGCS1的水平显著恢复。EA是肾茶中对草酸钙诱导的肾损伤具有保护作用的活性成分。SQLE、SCD和HMGCS1是EA的推定治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6962/9400657/3762c38510cd/fphar-13-891788-g001.jpg

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