Madecassoside Improves Renal Injury via Activation of AMPK/Autophagy in Experimental Membranous Nephropathy

IF 2.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Hongyan Liu, Yamei Ge, Zheng Wang, Hongyun Wang, Qiong Wang, Jun Yuan
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Abstract

Currently, membranous nephropathy (MN) has received considerable attention in Chine due to its increasing prevalence and limited therapeutic approaches. Madecassoside (MA) is a natural compound with anti-inflammatory, antioxidant, anticancer, and wound healing effects. In this study, we aimed to investigate the roles and related mechanisms of MA in MN. The passive Heymann nephritis (PHN) model was established in rats to mimic human MN. MA was intraperitoneally injected into MN rats beginning 1 week after modeling for 4 weeks. Urine, blood samples, and kidney samples were collected for biochemical analysis and histopathological analysis. Western blot analysis and immunofluorescence staining were performed. MA relieved MN-induced renal dysfunctions and histopathology in rats. Additionally, MA reduced IgG and C3 deposition and alleviated podocyte injury in MN rats. Moreover, MA activated canonical autophagy by modulating AMPK/mTOR. Furthermore, MA ameliorated oxidative stress and inflammation in renal tissues of MN model rats. In conclusion, treatment with MA ameliorates proteinuria and renal dysfunctions in MN rats by activating AMPK/mTOR-mediated autophagy.

马栀子苷通过激活AMPK/自噬改善实验性膜性肾病的肾损伤
目前,膜性肾病(MN)由于其日益增加的患病率和有限的治疗方法在中国受到了相当大的关注。马钱子皂苷(MA)是一种具有抗炎、抗氧化、抗癌和伤口愈合作用的天然化合物。在本研究中,我们旨在探讨MA在MN中的作用及其相关机制。建立大鼠被动海曼肾炎(PHN)模型,模拟人MN。造模4周后1周开始向MN大鼠腹腔注射MA。收集尿液、血液、肾脏样本进行生化分析和组织病理学分析。Western blot分析和免疫荧光染色。MA对mn所致大鼠肾功能及组织病理学的影响有缓解作用。此外,MA可减少MN大鼠IgG和C3沉积,减轻足细胞损伤。此外,MA通过调节AMPK/mTOR激活典型自噬。此外,MA还能改善MN模型大鼠肾组织的氧化应激和炎症。综上所述,MA通过激活AMPK/ mtor介导的自噬来改善MN大鼠的蛋白尿和肾功能障碍。
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来源期刊
CiteScore
5.80
自引率
2.80%
发文量
277
审稿时长
6-12 weeks
期刊介绍: The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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