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The Modified Shen-Yan-Fang-Shuai formula (M-SYFSF) shows clinical efficacy, yet its mechanism is unclear. This study tests whether M-SYFSF protects DKD by modulating HIF-1α–mediated mitochondrial energy metabolism.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/modified-shen-yan-fang-shuai-formula-attenuates-diabetic-kidney-disease-progression-via-regulation-of-hif-1-mediated-mitochondrial-energy-metabolism/460955/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/modified-shen-yan-fang-shuai-formula-attenuates-diabetic-kidney-disease-progression-via-regulation-of-hif-1-mediated-mitochondrial-energy-metabolism/460955.png","ImageObject",300,407,{"name":92,"@type":93},"Jordan Avery","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the study target?","Question",{"text":112,"@type":113},"The study targets diabetic kidney disease (DKD), a major global health burden and a leading cause of chronic kidney disease worldwide.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What experimental models and interventions are used?",{"text":117,"@type":113},"A streptozotocin-induced DKD rat model with unilateral nephrectomy is used, and M-SYFSF is administered for 12 weeks. An in vitro model uses HK-2 cells treated with advanced glycation end products under hypoxic conditions, including HIF-1α overexpression and knockdown.",{"name":119,"@type":110,"acceptedAnswer":120},"How does M-SYFSF affect the HIF-1α pathway and mitochondrial metabolism?",{"text":121,"@type":113},"M-SYFSF suppresses HIF-1α expression and nuclear translocation and shifts metabolism from glycolysis toward oxidative phosphorylation, improving mitochondrial ATP production and mitochondrial structure and respiratory chain complex activities.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},460955,1791067039,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":26,"preview_page_count":4},1099523882367,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Di et al. Chinese Medicine (2026) 21:23 [https://doi.org/10.1186/s13020-025-01298-5](https://doi.org/10.1186/s13020-025-01298-5)  \nChinese Medicine  \n RESEARCH Open Access  \nModified Shen-Yan-Fang-Shuai formula  \nattenuates diabetic kidney disease progression via regulation of HIF-1α-mediated mitochondrial energy metabolism  \nBingnan Di1,2†, Yaotan Li1,3†, Jinyan Wei5, Yizhen Han6, Jinyi Hou1,3, Xinghua Zhang1,3, Xiaochang Wu1,3, Weijing Liu1,3*, Huijuan Zheng1,3* and Yaoxian Wang1,3,4*  \nAbstract  \nBackground Diabetic kidney disease (DKD) represents a major global health burden, affecting 20–40% of diabetic patients worldwide. Metabolic reprogramming mediated by hypoxia-inducible factor-1α (HIF-1α) plays a central role in DKD pathogenesis, yet effective therapeutic strategies remain limited. The Modified Shen-Yan-Fang-Shuai formula (M-SYFSF), a traditional Chinese medicine formulation, has demonstrated clinical efficacy in DKD treatment, but its underlying mechanisms remain unclear.  \nMethods A DKD model was established using streptozotocin-induced diabetic rats following unilateral nephrectomy. Thirty rats were randomly divided into sham operation, model, and M-SYFSF treatment groups (n = 10/group) . M-SYFSF was administered at 11.34 g/kg/d for 12 weeks. Renal function, histopathology, oxidative stress markers, and metabolic parameters were assessed. Human proximal tubular epithelial cells (HK-2) were treated with advanced glycation end products under hypoxic conditions to establish an in vitro DKD model. HIF-1α overexpression and knockdown experiments were performed to investigate molecular mechanisms. Key glycolytic enzymes, mitochondrial dynamics proteins, and bioenergetic parameters were analyzed using Western blot, immunohistochemistry, immunofluorescence, and metabolic assays.  \nResults M-SYFSF treatment significantly improved renal function parameters, reducing serum creatinine (p \u003C 0. 001) and proteinuria (p \u003C 0. 001) while ameliorating characteristic DKD histopathological changes. M-SYFSF effectively suppressed HIF-1α expression and nuclear translocation, accompanied by consistent downregulation of key glycolytic enzymes including hexokinase 2, lactate dehydrogenase, and pyruvate dehydrogenase kinase 1. Metabolic analysis revealed that M-SYFSF promoted a shift from glycolysis toward oxidative phosphorylation, restoring mitochondrial ATP production capacity. Transmission electron microscopy demonstrated that M-SYFSF preserved mitochondrial ultrastructure and improved mitochondrial respiratory chain complex activities (I, III, and IV; all p \u003C 0. 01) . M-SYFSF  \n†Bingnan Di and Yaotan Li have contributed equally to this article.  \n*Correspondence:  \nWeijing Liu [liuweijing-1977@hotmail.com](liuweijing-1977@hotmail.com)[ ](liuweijing-1977@hotmail.com)Huijuan Zheng [tcmzhenghuijuan@163.com](tcmzhenghuijuan@163.com)[ ](tcmzhenghuijuan@163.com)Yaoxian Wang [wyx3203@sina.com](wyx3203@sina.com)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[","cbCaikMw7Te4DZ61","https://ap.wps.com/l/cbCaikMw7Te4DZ61","pdf",14706606,24,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"What problem does the study target?\",\"answer\":\"The study targets diabetic kidney disease (DKD), a major global health burden and a leading cause of chronic kidney disease worldwide.\"},{\"question\":\"What experimental models and interventions are used?\",\"answer\":\"A streptozotocin-induced DKD rat model with unilateral nephrectomy is used, and M-SYFSF is administered for 12 weeks. An in vitro model uses HK-2 cells treated with advanced glycation end products under hypoxic conditions, including HIF-1α overexpression and knockdown.\"},{\"question\":\"How does M-SYFSF affect the HIF-1α pathway and mitochondrial metabolism?\",\"answer\":\"M-SYFSF suppresses HIF-1α expression and nuclear translocation and shifts metabolism from glycolysis toward oxidative phosphorylation, improving mitochondrial ATP production and mitochondrial structure and respiratory chain complex activities.\"}]","Modified Shen-Yan-Fang-Shuai formula - attenuates diabetic kidney disease progression via regulation of HIF-1α-mediated mitochondrial energy metabolism | PDF",1790760162]