关键词: Orthosiphon aristatus (Blume) Miq. diabetic nephropathy ferroptosis gut microbiota serum metabolites

来  源:   DOI:10.3389/fphar.2024.1392123   PDF(Pubmed)

Abstract:
UNASSIGNED: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Due to its complex pathogenesis, new therapeutic agents are urgently needed. Orthosiphon aristatus (Blume) Miq., commonly known as kidney tea, is widely used in DN treatment in China. However, the mechanisms have not been fully elucidated.
UNASSIGNED: 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.
UNASSIGNED: 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 Muribaculaceae, Lachnoclostridium, Prevotellaceae_UCG-001, Corynebacterium and Akkermansia, and enriched the abundance of Alloprevotella, Blautia and Lachnospiraceae_NK4A136_group. 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.
UNASSIGNED: 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.
摘要:
糖尿病肾病(DN)是终末期肾病的主要原因。由于其复杂的发病机制,迫切需要新的治疗药物。正交虹吸状态(蓝色)Miq。,通常被称为肾茶,在国内广泛应用于DN治疗。然而,机制尚未完全阐明。
我们使用db/db小鼠作为DN模型,并通过测量空腹血糖(FBG)来评估肾茶在DN治疗中的功效,血清炎性细胞因子,肾损伤指标及组织病理学改变。此外,16SrDNA基因测序,非靶向血清代谢组学,电子显微镜,ELISA,qRT-PCR,并进行蛋白质印迹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FBG,DN小鼠的炎症和肾损伤。此外,肾茶重塑了肠道微生物群,减少了Muribaculaceae的丰度,衣原体,Prevotellaceae_UCG-001,棒状杆菌和Akkermansia,丰富了大量的Alloprevotella,布劳特氏菌和蛇床子科_NK4A136_组。肾茶改变了铁凋亡等途径中血清代谢物的水平,精氨酸生物合成与mTOR信号通路.重要的是,肾茶改善线粒体损伤,增加SOD活性,并降低了DN小鼠肾组织中MDA和4-HNE的水平。同时,该功能性茶上调GPX4和FTH1表达,下调ACSL4和NCOA4表达,表明它可以抑制肾脏的铁性凋亡。
我们的发现暗示肾茶可以通过调节肠道菌群和铁死亡来减弱DN的发育,这为肾茶的临床应用提供了新的科学依据。
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