Wei Quan-Hao, Pan Yin-Bo, Tian Lin-Lin, Wang Yu-Song, Wang Jin-Yan, Liu Xiang, Zhang Hua
School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, China; School of Biological Science and Technology, University of Jinan, Jinan, 250022, China.
School of Biological Science and Technology, University of Jinan, Jinan, 250022, China.
Phytomedicine. 2025 Jan;136:156351. doi: 10.1016/j.phymed.2024.156351. Epub 2024 Dec 27.
Renal fibrosis is a major pathological feature of many chronic kidney diseases, and traditional Chinese medicines (TCM) have shown promising therapeutic potential for treating renal fibrosis. Although the extracts or fractions of Morus alba leaves and twigs have been reported to ameliorate renal fibrosis, the beneficial effects of M. alba root bark (commonly known as Sang-Bai-Pi), a well-known TCM, on this disorder have not been investigated.
This study aims to investigate the effects and mechanisms of Sang-Bai-Pi extract/fractions and their constituents on renal fibrosis.
Immunoblotting was first used to assess the effects of different Sang-Bai-Pi fractions on key fibrotic markers. The most potent fraction, EA-3, was further evaluated using a unilateral ureteral obstruction (UUO) rat model to assess its antifibrotic effects. The efficacy of EA-3 was evaluated by analyzing the pathomorphological changes in the kidney tissues of rats using histological staining and by detecting the expression of relevant proteins via Western blotting. The transforming growth factor-β1 (TGF-β1)-stimulated human renal proximal tubular cell line HK-2 was used to elucidate the likely modes of action of EA-3 and its constituent regiafuran C (RFC). Network pharmacology and molecular docking analyses were utilized to explore the detailed molecular mechanism of RFC.
Fraction EA3 effectively alleviated UUO-induced renal fibrosis in rats. Mechanistically, EA-3 suppressed the epithelial-mesenchymal transition, accumulation of extracellular matrix, and activation of the TGF-β/Smad and Wnt/β-catenin signaling pathways in vitro and in vivo. RFC also demonstrated antifibrotic potential by inhibiting TGF-β/Smad and Wnt/β-catenin signaling in HK-2 cells. Further investigations revealed that RFC inhibited TGF-β/Smad pathway by blocking the interaction of Smad3 with TGF-βRII and TGF-βRI might be a potential direct target of RFC.
The antirenal fibrotic effects of Sang-Bai-Pi extract/fractions and the constituent RFC were evaluated for the first time. Fraction EA-3 and RFC alleviated renal fibrosis by targeting the TGF-β/Smad and Wnt/β-catenin pathways. These findings provide valuable insights into the development of Sang-Bai-Pi-based phytotherapy and new drug molecules for the safe treatment of renal diseases.
肾纤维化是许多慢性肾脏病的主要病理特征，中药已显示出治疗肾纤维化的潜在治疗潜力。尽管已报道桑叶和桑枝的提取物或馏分可改善肾纤维化，但著名中药桑白皮对该疾病的有益作用尚未得到研究。
本研究旨在探讨桑白皮提取物/馏分及其成分对肾纤维化的影响及机制。
首先采用免疫印迹法评估不同桑白皮馏分对关键纤维化标志物的影响。使用单侧输尿管梗阻（UUO）大鼠模型进一步评估最有效的馏分EA-3的抗纤维化作用。通过组织学染色分析大鼠肾组织的病理形态学变化，并通过蛋白质印迹法检测相关蛋白的表达，评估EA-3的疗效。使用转化生长因子-β1（TGF-β1）刺激的人肾近端小管细胞系HK-2来阐明EA-3及其成分雷加呋喃C（RFC）可能的作用方式。利用网络药理学和分子对接分析来探索RFC的详细分子机制。
馏分EA3有效减轻了UUO诱导的大鼠肾纤维化。从机制上讲，EA-3在体外和体内均抑制上皮-间质转化、细胞外基质积累以及TGF-β/Smad和Wnt/β-连环蛋白信号通路的激活。RFC通过抑制HK-2细胞中的TGF-β/Smad和Wnt/β-连环蛋白信号也显示出抗纤维化潜力。进一步研究表明，RFC通过阻断Smad3与TGF-βRII的相互作用来抑制TGF-β/Smad通路，TGF-βRI可能是RFC的潜在直接靶点。
首次评估了桑白皮提取物/馏分及其成分RFC的抗肾纤维化作用。馏分EA-3和RFC通过靶向TGF-β/Smad和Wnt/β-连环蛋白通路减轻肾纤维化。这些发现为基于桑白皮的植物疗法和用于安全治疗肾脏疾病的新药物分子的开发提供了有价值的见解。
