Department of Nephrology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing city, Jiangsu, China.
Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Jiangsu, China.
Ren Fail. 2024 Dec;46(2):2398710. doi: 10.1080/0886022X.2024.2398710. Epub 2024 Sep 5.
This study aimed to investigate the inhibitory effect of chrysophanol on renal fibrosis and its molecular mechanism.
Initially, potential targets of chrysophanol were predicted through network pharmacology analysis, and a protein-protein interaction network of these targets was constructed using Venn diagrams and the STRING database. GO enrichment analysis predicted the biological process of chrysophanol in treating renal fibrosis. Subsequently, both and experiments were conducted using unilateral ureteral obstruction (UUO) induced CKD mouse model and HK-2 cell model, respectively. In the mouse model, different doses of chrysophanol were administered to assess its renal protective effects through biochemical indicators, histological examination, and immunofluorescence staining. In the cell model, the regulatory effect of chrysophanol on the Trx-1/JNK/Cx43 pathway was evaluated using western blotting and flow cytometry.
Chrysophanol treatment significantly ameliorated renal dysfunction and histopathological damage in the UUO mouse model, accompanied by a reduction in serum oxidative stress markers. Furthermore, chrysophanol markedly upregulated the expression of Trx-1 in renal tissues and inhibited the activation of the JNK/Cx43 signaling pathway. At the cellular level, chrysophanol enhanced the activity of Trx-1 and downregulated the JNK/Cx43 signaling pathway, thereby inhibiting TGF-β induced oxidative stress and cell apoptosis.
This study demonstrated a significant inhibitory effect of chrysophanol on renal fibrosis, mediated by the activation of Trx-1 to inhibit the JNK/Cx43 pathway. These findings provide experimental support for the potential use of chrysophanol as a therapeutic agent for renal fibrosis.
本研究旨在探讨大黄素抑制肾纤维化的作用及其分子机制。
首先，通过网络药理学分析预测大黄素的潜在靶点，并使用 Venn 图和 STRING 数据库构建这些靶点的蛋白质-蛋白质相互作用网络。GO 富集分析预测了大黄素治疗肾纤维化的生物学过程。随后，分别采用单侧输尿管梗阻（UUO）诱导的 CKD 小鼠模型和 HK-2 细胞模型进行 和 实验。在小鼠模型中，给予不同剂量的大黄素，通过生化指标、组织学检查和免疫荧光染色评估其肾脏保护作用。在细胞模型中，通过 Western blot 和流式细胞术评估大黄素对 Trx-1/JNK/Cx43 通路的调节作用。
大黄素治疗显著改善了 UUO 小鼠模型的肾功能和组织病理学损伤，同时降低了血清氧化应激标志物水平。此外，大黄素明显上调了肾组织中 Trx-1 的表达，并抑制了 JNK/Cx43 信号通路的激活。在细胞水平上，大黄素增强了 Trx-1 的活性，下调了 JNK/Cx43 信号通路，从而抑制了 TGF-β诱导的氧化应激和细胞凋亡。
本研究表明大黄素对肾纤维化具有显著的抑制作用，其机制可能是通过激活 Trx-1 抑制 JNK/Cx43 通路。这些发现为大黄素作为肾纤维化治疗药物的潜在应用提供了实验依据。
