Zhou Zheng, Niu Hongjuan, Bian Meng, Zhu Chunsheng
Department of Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
Front Pharmacol. 2024 Jun 19;15:1392123. doi: 10.3389/fphar.2024.1392123. eCollection 2024.
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Due to its complex pathogenesis, new therapeutic agents are urgently needed. (Blume) Miq., commonly known as kidney tea, is widely used in DN treatment in China. However, the mechanisms have not been fully elucidated.
We used db/db mice as the DN model and evaluated the efficacy of kidney tea in DN treatment by measuring fasting blood glucose (FBG), serum inflammatory cytokines, renal injury indicators and histopathological changes. Furthermore, 16S rDNA gene sequencing, untargeted serum metabolomics, electron microscope, ELISA, qRT-PCR, and Western blotting were performed to explore the mechanisms by which kidney tea exerted therapeutic effects.
Twelve polyphenols were identified from kidney tea, and its extract ameliorated FBG, inflammation and renal injury in DN mice. Moreover, kidney tea reshaped the gut microbiota, reduced the abundance of , , , and , and enriched the abundance of , and . Kidney tea altered the levels of serum metabolites in pathways such as ferroptosis, arginine biosynthesis and mTOR signaling pathway. Importantly, kidney tea improved mitochondrial damage, increased SOD activity, and decreased the levels of MDA and 4-HNE in the renal tissues of DN mice. Meanwhile, this functional tea upregulated GPX4 and FTH1 expression and downregulated ACSL4 and NCOA4 expression, indicating that it could inhibit ferroptosis in the kidneys.
Our findings imply that kidney tea can attenuate DN development by modulating gut microbiota and ferroptosis, which presents a novel scientific rationale for the clinical application of kidney tea.
糖尿病肾病（DN）是终末期肾病的主要原因。由于其发病机制复杂，迫切需要新的治疗药物。肾茶（Blume）Miq.，俗称肾茶，在中国广泛用于DN的治疗。然而，其机制尚未完全阐明。
我们使用db/db小鼠作为DN模型，通过测量空腹血糖（FBG）、血清炎症细胞因子、肾损伤指标和组织病理学变化来评估肾茶在DN治疗中的疗效。此外，还进行了16S rDNA基因测序、非靶向血清代谢组学、电子显微镜、酶联免疫吸附测定（ELISA）、实时定量聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法，以探讨肾茶发挥治疗作用的机制。
从肾茶中鉴定出12种多酚，其提取物改善了DN小鼠的FBG、炎症和肾损伤。此外，肾茶重塑了肠道微生物群，降低了[具体菌属1]、[具体菌属2]、[具体菌属3]、[具体菌属4]和[具体菌属5]的丰度，并增加了[具体菌属6]、[具体菌属7]和[具体菌属8]的丰度。肾茶改变了铁死亡、精氨酸生物合成和mTOR信号通路等途径中的血清代谢物水平。重要的是，肾茶改善了线粒体损伤，增加了超氧化物歧化酶（SOD）活性，并降低了DN小鼠肾组织中丙二醛（MDA）和4-羟基壬烯醛（4-HNE）的水平。同时，这种功能性茶上调了谷胱甘肽过氧化物酶4（GPX4）和铁蛋白重链1（FTH1）的表达，下调了长链脂酰辅酶A合成酶4（ACSL4）和核受体辅激活因子4（NCOA4）的表达表明它可以抑制肾脏中的铁死亡。
我们的研究结果表明，肾茶可以通过调节肠道微生物群和铁死亡来减轻DN的发展，这为肾茶的临床应用提供了新的科学依据。
