Background: Renal tubulointerstitial fibrosis (RTF) is a progressive kidney condition characterized by the formation of fibrotic tissue. Caffeic acid (CA), a key component of the medicinal plant Antirhea borbonica, shows promise as a potential treatment for renal fibrosis. Here, we investigated the nephroprotective effect of CA in RTF and its underlying mechanisms. Methods: RTF was induced in rats through unilateral ureteral obstruction (UUO), followed by intraperitoneal administration of CA for 5 days. We assessed kidney weight/body weight (KW/BW) ratio, serum creatinine (Scr), blood urea nitrogen (BUN), 24-h urine protein (UP), and performed histological examinations. We also analyzed the expression of fibrosis-related proteins. Genes associated with RTF and CA were identified using public databases. A protein-protein interaction (PPI) network and molecular docking studies were conducted. Results: CA treatment significantly reduced the KW/BW ratio, levels of Scr, BUN, and 24-h UP, indicating improved kidney function in UUO-induced RTF rats. Histological examination revealed reduced fibrotic changes. CA administration also led to decreased collagen deposition and downregulation of fibrosis-related protein expression. CA administration also led to decreased collagen deposition and downregulation of fibrosis-related protein expression. The PPI network analysis showed significant differential expression of 13 genes between the fibrosis and normal groups. Notably, EGFR and MAPK14 were strongly associated with CA, and CA treatment downregulated EGFR and MAPK14 protein expression in UUO rats. Conclusion: CA exhibits substantial nephroprotective effects in UUO-induced RTF rats by modulating key genes EGFR and MAPK14, and MAPK signaling pathway.

中文翻译：

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通过网络药理学分析揭示咖啡酸对肾小管间质纤维化的肾保护机制

背景：肾小管间质纤维化（RTF）是一种进行性肾脏疾病，其特征是纤维化组织的形成。咖啡酸 (CA) 是药用植物 Antirhea borbonica 的关键成分，有望成为治疗肾纤维化的潜在药物。在这里，我们研究了 RTF 中 CA 的肾保护作用及其潜在机制。方法：通过单侧输尿管梗阻（UUO）诱导大鼠RTF，然后腹腔注射CA 5天。我们评估了肾重/体重（KW/BW）比、血清肌酐（Scr）、血尿素氮（BUN）、24小时尿蛋白（UP），并进行了组织学检查。我们还分析了纤维化相关蛋白的表达。使用公共数据库鉴定了与 RTF 和 CA 相关的基因。进行了蛋白质-蛋白质相互作用（PPI）网络和分子对接研究。结果：CA 治疗显着降低了 KW/BW 比值、Scr、BUN 和 24 小时 UP 水平，表明 UUO 诱导的 RTF 大鼠的肾功能得到改善。组织学检查显示纤维化变化减少。CA 给药还导致胶原蛋白沉积减少和纤维化相关蛋白表达下调。CA 给药还导致胶原蛋白沉积减少和纤维化相关蛋白表达下调。PPI网络分析显示纤维化组和正常组之间有13个基因表达存在显着差异。值得注意的是，EGFR 和 MAPK14 与 CA 密切相关，CA 治疗下调 UUO 大鼠中 EGFR 和 MAPK14 蛋白表达。结论：CA通过调节关键基因EGFR和MAPK14以及MAPK信号通路对UUO诱导的RTF大鼠表现出显着的肾保护作用。