Zhu Rong, Zheng Rong, Deng Yueyi, Chen Yiping, Zhang Shuwei
Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Phytomedicine. 2014 Feb 15;21(3):372-8. doi: 10.1016/j.phymed.2013.08.022. Epub 2013 Oct 3.
Chronic kidney disease is a growing public health problem with an urgent need for new pharmacological agents. Ergosterol peroxide (EP) is the major sterol produced by Cordyceps cicadae Shing (C. cicadae), a widely used traditional Chinese medicine. C. cicadae has been used to treat many kinds of diseases and has a potential benefit on renoprotection. This study aimed to investigate the anti-fibrotic effects of EP as well as the underlying mechanisms. A normal rat kidney fibroblast cell line (NRK-49F) was stimulated to undergo fibroblast activation by transforming growth factor-β1 (TGF-β1) and EP treatment was applied to explore its potential anti-fibrotic effects. Cell proliferation was investigated using MTT analysis. Fibrosis-associated protein expression was analyzed using immunohistochemistry and/or Western blotting. EP treatment attenuated TGF-β1-induced renal fibroblast proliferation, expression of cytoskeleton protein and CTGF, as well as ECM production. Additionally, EP blocked TGF-β1-stimulated phosphorylation of ERK1/2, p38 and JNK pathway. Moreover, the TGF-β1-induced expression of fibronectin was attenuated by either inhibition of MAPKs or by EP treatment. In conclusion, our findings demonstrate that EP is able to suppress TGF-β1-induced fibroblasts activation in NRK-49F. This new information provides a line of theoretical evidence supporting the use of C. cicadae in the intervention of kidney disease and suggests that EP has the potential to be developed as a therapeutic agent to prevent renal fibrosis.
慢性肾病是一个日益严重的公共卫生问题，迫切需要新的药物制剂。过氧化麦角甾醇（EP）是蝉花（C. cicadae）产生的主要甾醇，蝉花是一种广泛应用的传统中药。蝉花已被用于治疗多种疾病，对肾脏具有潜在的保护作用。本研究旨在探讨EP的抗纤维化作用及其潜在机制。采用转化生长因子-β1（TGF-β1）刺激正常大鼠肾成纤维细胞系（NRK-49F）使其发生成纤维细胞活化，并应用EP处理以探究其潜在的抗纤维化作用。通过MTT分析研究细胞增殖情况。使用免疫组织化学和/或蛋白质印迹法分析纤维化相关蛋白的表达。EP处理可减弱TGF-β1诱导的肾成纤维细胞增殖、细胞骨架蛋白和结缔组织生长因子（CTGF）的表达以及细胞外基质（ECM）的产生。此外，EP可阻断TGF-β1刺激的细胞外信号调节激酶1/2（ERK1/2）、p38和c-Jun氨基末端激酶（JNK）通路的磷酸化。而且，通过抑制丝裂原活化蛋白激酶（MAPKs）或EP处理均可减弱TGF-β1诱导的纤连蛋白表达。总之，我们的研究结果表明，EP能够抑制TGF-β1诱导的NRK-49F成纤维细胞活化。这一新信息为支持蝉花用于肾脏疾病干预提供了一系列理论证据，并表明EP有潜力被开发成为预防肾纤维化的治疗药物。
