{"title":"Astragaloside IV Protects against Diabetic Nephropathy by Inhibiting FUNDC1-Dependent Mitochondria-Associated Endoplasmic Reticulum Membranes","authors":"Zeng Zhang, Yanyan Wang, Fengzhu Zhou, Siyu Xu, Xinyi Zhang, Yueying Ma, Yifei Liu, Yanming He","doi":"10.1155/2024/2602406","DOIUrl":null,"url":null,"abstract":"<div>\n <p>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 Ca<sup>2+</sup> 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.</p>\n </div>","PeriodicalId":15802,"journal":{"name":"Journal of Food Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/2602406","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Food Biochemistry","FirstCategoryId":"97","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/2024/2602406","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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