Abstract Context Renal interstitial fibrosis (RIF) is characterized by the accumulation of inflammatory cytokines and epithelial-mesenchymal transition (EMT). Curcumin exerts antifibrogenic, anti-inflammatory and antiproliferative effects. Objective To explore the mechanisms underlying the effects of curcumin on RIF. Materials and methods Eight-week-old male C57BL/6 mice were intragastrically administered curcumin (50 mg/kg/day) for 14 days after undergoing unilateral ureteral obstruction (UUO) operations. Renal function (blood urea nitrogen [BUN] and serum creatinine [Scr]) and inflammatory cytokine levels were tested using colorimetric assays and ELISA, respectively. EMT markers were evaluated through immunohistochemistry, western blotting and qPCR. Transforming growth factor beta 1 (TGF-β1; 10 ng/mL) and lipopolysaccharides (LPS; 100 ng/mL) were used to stimulate EMT and an inflammatory response in human renal proximal tubular epithelial (HK-2) cells, respectively, for further investigation. Results In vivo, curcumin significantly improved the levels of BUN and Scr by 28.7% and 21.3%, respectively. Moreover, curcumin reduced the levels of IL-6, IL-1β and TNF-α by 22.5%, 30.3% and 26.7%, respectively, and suppressed vimentin expression in UUO mice. In vitro, curcumin reduced the expression of vimentin and α-smooth muscle actin in TGF-β1-induced HK-2 cells. In LPS-induced HK-2 cells, curcumin decreased the release of IL-6, IL-1β and TNF-α by 43.4%, 38.1% and 28.3%, respectively. In addition, curcumin reduced the expression of TLR4, p-PI3K, p-AKT, p-NF- κB and p-IκBα in both LPS- and TGF-β1-induced HK-2 cells. Discussion and conclusions Curcumin repressed EMT and the inflammatory response by inhibiting the TLR4/NF-κB and PI3K/AKT pathways, demonstrating its potential utility in RIF treatment.

中文翻译：

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姜黄素通过抑制 TLR4/NF-кB 和 PI3K/AKT 信号通路抑制上皮间质转化，从而减轻阻塞性肾病的肾间质纤维化

摘要背景肾间质纤维化 (RIF) 的特征是炎性细胞因子的积累和上皮间质转化 (EMT)。姜黄素具有抗纤维化、抗炎和抗增殖作用。目的探讨姜黄素对RIF影响的机制。材料和方法 八周大的雄性 C57BL/6 小鼠在接受单侧输尿管梗阻 (UUO) 手术后，灌胃姜黄素 (50 毫克/公斤/天) 14 天。分别使用比色法和 ELISA 测试肾功能（血尿素氮 [BUN] 和血清肌酐 [Scr]）和炎性细胞因子水平。EMT 标志物通过免疫组织化学、蛋白质印迹和 qPCR 进行评估。转化生长因子β1（TGF-β1；10 ng/mL）和脂多糖（LPS；100 ng/mL) 分别用于刺激人肾近端肾小管上皮 (HK-2) 细胞的 EMT 和炎症反应，以进行进一步研究。结果 在体内，姜黄素使 BUN 和 Scr 的水平分别显着提高了 28.7% 和 21.3%。此外，姜黄素使 IL-6、IL-1β 和 TNF-α 的水平分别降低了 22.5%、30.3% 和 26.7%，并抑制了 UUO 小鼠的波形蛋白表达。在体外，姜黄素降低了 TGF-β1 诱导的 HK-2 细胞中波形蛋白和α-平滑肌肌动蛋白的表达。在 LPS 诱导的 HK-2 细胞中，姜黄素使 IL-6、IL-1β 和 TNF-α 的释放分别减少 43.4%、38.1% 和 28.3%。此外，姜黄素降低了 LPS 和 TGF-β1 诱导的 HK-2 细胞中 TLR4、p-PI3K、p-AKT、p-NF-κB 和 p-IκBα 的表达。