Department of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, 110022, China.
Eur J Pharmacol. 2023 Jul 5;950:175771. doi: 10.1016/j.ejphar.2023.175771. Epub 2023 May 3.
Imperata cylindrica, a medicinal plant used in Traditional Chinese Medicine, has been used to treat chronic kidney disease. Extracts of I. cylindrica display anti-inflammatory, immunomodulatory, and anti-fibrotic properties. However, the active components of the extracts and their protective mechanisms have not been fully elucidated. In this study, we explored the ability of cylindrin, the main active compound extracted from I. cylindrica, to protect against renal fibrosis and to investigate the potential mechanisms involved. At high doses, cylindrin exerted protective effects against folic acid-induced kidney fibrosis in mice. Bioinformatic analysis predicted the LXR-α/PI3K/AKT pathway as a target of regulation by cylindrin. This was supported by our in vitro and in vivo results showing that cylindrin significantly downregulated the expression of LXR-α and phosphorylated PI3K/AKT in M2 macrophages and mouse renal tissues. Furthermore, high-dose cylindrin inhibited M2 polarization of IL-4-stimulated macrophages in vitro. Our results suggest that cylindrin alleviates renal fibrosis by attenuating M2 macrophage polarization through inhibition of the PI3K/AKT pathway via downregulation of LXR-α.
白茅根，一种用于中药的药用植物，已被用于治疗慢性肾病。白茅根提取物具有抗炎、免疫调节和抗纤维化特性。然而，提取物的活性成分及其保护机制尚未完全阐明。在这项研究中，我们探讨了从白茅根中提取的主要活性化合物圆柱菌素在防治肾纤维化方面的作用及其潜在机制。在高剂量下，圆柱菌素对叶酸诱导的小鼠肾纤维化具有保护作用。生物信息学分析预测 LXR-α/PI3K/AKT 通路是圆柱菌素调节的靶点。这一预测得到了我们的体外和体内实验结果的支持，结果表明圆柱菌素显著下调了 M2 巨噬细胞和小鼠肾组织中 LXR-α和磷酸化 PI3K/AKT 的表达。此外，高剂量的圆柱菌素在体外抑制了 IL-4 刺激的巨噬细胞向 M2 极化。我们的研究结果表明，圆柱菌素通过下调 LXR-α抑制 PI3K/AKT 通路，减轻 M2 巨噬细胞极化，从而缓解肾纤维化。
