Astragaloside IV Protects against Diabetic Nephropathy by Inhibiting FUNDC1-Dependent Mitochondria-Associated Endoplasmic Reticulum Membranes

IF 3.5 2区 农林科学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Zeng Zhang, Yanyan Wang, Fengzhu Zhou, Siyu Xu, Xinyi Zhang, Yueying Ma, Yifei Liu, Yanming He
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Abstract

Studies have demonstrated the potential therapeutic effects of Astragaloside IV (AS-IV) in various diseases. However, its effect on diabetic nephropathy (DN) and the underlying mechanisms are not clear. The expression of FUNDC1 in DN patients and high glucose-induced human renal tubular epithelial cell line (HK-2) with or without AS-IV was analyzed using quantitative real-time polymerase chain reaction and Western blot. Cell Counting Kit-8 (CCK-8) assay was used to quantify cell viability. The intracellular oxygen consumption rate was measured by using the seahorse energy analyzer, and the mitochondrial reactive oxygen species and mitochondrial Ca2+ levels were determined by flow cytometry. A mice model of diabetes was constructed and treated with different doses of AS-IV. Hematoxylin-eosin and Masson staining were used to examine the pathological changes in renal tissue. Creatinine, blood urea nitrogen, and urinary protein were detected by the biochemical method. The results demonstrated increased FUNDC1 expression in patients with DN and high glucose-cultured HK-2 cells. FUNDC1 silencing inhibited high glucose-induced mitochondria-associated endoplasmic reticulum (ER) membrane formation and mitochondrial dysfunction in HK-2 cells. Importantly, AS-IV treatment inhibited FUNDC1-induced mitochondria-associated ER membrane formation and mitochondrial dysfunction in HK-2 cells. AS-IV treatment also protected against renal injury and improved renal function in mice. AS-IV alleviates the progression of DN by inhibiting FUNDC1-dependent mitochondria-associated ER membrane.

Abstract Image

黄芪皂苷 IV 通过抑制 FUNDC1 依赖性线粒体相关内质网膜保护糖尿病肾病
研究表明,黄芪皂苷 IV(AS-IV)对多种疾病具有潜在的治疗作用。然而,它对糖尿病肾病(DN)的作用及其机制尚不清楚。本研究采用实时定量聚合酶链反应和 Western 印迹法分析了 FUNDC1 在糖尿病肾病患者和高糖诱导的人肾小管上皮细胞系(HK-2)中的表达情况。细胞计数试剂盒-8(CCK-8)测定法用于量化细胞活力。海马能量分析仪测定了细胞内耗氧量,流式细胞仪测定了线粒体活性氧和线粒体 Ca2+ 水平。构建糖尿病小鼠模型并用不同剂量的 AS-IV 治疗。采用苏木精-伊红和马森染色法检测肾组织的病理变化。生化方法检测肌酐、血尿素氮和尿蛋白。结果表明,FUNDC1在DN患者和高糖培养的HK-2细胞中表达增加。沉默 FUNDC1 可抑制高糖诱导的线粒体相关内质网(ER)膜形成和 HK-2 细胞线粒体功能障碍。重要的是,AS-IV 可抑制 FUNDC1 诱导的线粒体相关内质网(ER)膜形成和 HK-2 细胞线粒体功能障碍。AS-IV 还能保护小鼠免受肾损伤并改善其肾功能。AS-IV通过抑制FUNDC1依赖的线粒体相关ER膜,缓解了DN的进展。
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来源期刊
Journal of Food Biochemistry
Journal of Food Biochemistry 生物-生化与分子生物学
CiteScore
7.80
自引率
5.00%
发文量
488
审稿时长
3.6 months
期刊介绍: The Journal of Food Biochemistry publishes fully peer-reviewed original research and review papers on the effects of handling, storage, and processing on the biochemical aspects of food tissues, systems, and bioactive compounds in the diet. Researchers in food science, food technology, biochemistry, and nutrition, particularly based in academia and industry, will find much of great use and interest in the journal. Coverage includes: -Biochemistry of postharvest/postmortem and processing problems -Enzyme chemistry and technology -Membrane biology and chemistry -Cell biology -Biophysics -Genetic expression -Pharmacological properties of food ingredients with an emphasis on the content of bioactive ingredients in foods Examples of topics covered in recently-published papers on two topics of current wide interest, nutraceuticals/functional foods and postharvest/postmortem, include the following: -Bioactive compounds found in foods, such as chocolate and herbs, as they affect serum cholesterol, diabetes, hypertension, and heart disease -The mechanism of the ripening process in fruit -The biogenesis of flavor precursors in meat -How biochemical changes in farm-raised fish are affecting processing and edible quality
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