Modified huangfeng decoction alleviates diabetic nephropathy by activating autophagy and regulating the gut microbiota

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-03-20 DOI:10.1016/j.phymed.2025.156677

Yinhua Ni , Wenlong Yang , Sisi Wang , Yuxiang Pan , Haimei Du , Liujie Zheng , Cheguo Cai , Zhengwei Fu , Qiang He , Juan Jin , Peipei Zhang

{"title":"Modified huangfeng decoction alleviates diabetic nephropathy by activating autophagy and regulating the gut microbiota","authors":"Yinhua Ni , Wenlong Yang , Sisi Wang , Yuxiang Pan , Haimei Du , Liujie Zheng , Cheguo Cai , Zhengwei Fu , Qiang He , Juan Jin , Peipei Zhang","doi":"10.1016/j.phymed.2025.156677","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Diabetic nephropathy (DN) is one of the complications with the highest mortality among diabetes patients and can lead to renal failure. Modified Huangfeng decoction (MHD) has been widely applied in the clinical treatment of kidney diseases. However, the mechanism by which MHD affects DN has not been fully elucidated.</div></div><div><h3>Purpose</h3><div>To investigate the impact of MHD on DN in mice and the underlying mechanism.</div></div><div><h3>Methods</h3><div>The main ingredients of MHD were identified by liquid chromatography‒mass spectrometry. A high-fat diet- and streptozotocin (STZ)-induced DN mouse model was constructed and treated with MHD for 6 weeks. The serum and urine parameters were measured, and the tissue sections were histologically stained. The mRNA and protein levels of metabolism-, inflammation-, fibrosis-, and autophagy-related markers were examined by qPCR and western blotting. The microbial composition and metabolites of cecal contents were analyzed through full-length 16S rRNA sequencing and nontargeted metabolomics.</div></div><div><h3>Results</h3><div>MHD alleviated insulin resistance in DN mice and ameliorated changes in lipid metabolism and inflammation in the liver and fat. In addition, MHD reduced the levels of kidney injury markers in the serum and urine and attenuated inflammation and fibrosis in the kidney. These results were accompanied by enhanced gut barrier function and a markedly altered microbiota composition and metabolites, with an increased abundance of beneficial bacterial species and metabolites. Moreover, MHD itself and the microbial metabolite spermidine reduced podocyte damage by activating autophagy via the PI3K/AKT/mTOR pathway.</div></div><div><h3>Conclusions</h3><div>MHD potentially ameliorated DN by activating podocyte autophagy via the PI3K/AKT/mTOR pathway and modulating the gut microbiota and its metabolites. Our findings provide a more comprehensive understanding of the mechanism of MHD and the involvement of the gut‒kidney interaction in the progression of DN, laying a theoretical foundation for the clinical application of MHD in DN treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156677"},"PeriodicalIF":6.7000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0944711325003174","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Diabetic nephropathy (DN) is one of the complications with the highest mortality among diabetes patients and can lead to renal failure. Modified Huangfeng decoction (MHD) has been widely applied in the clinical treatment of kidney diseases. However, the mechanism by which MHD affects DN has not been fully elucidated.

Purpose

To investigate the impact of MHD on DN in mice and the underlying mechanism.

Methods

The main ingredients of MHD were identified by liquid chromatography‒mass spectrometry. A high-fat diet- and streptozotocin (STZ)-induced DN mouse model was constructed and treated with MHD for 6 weeks. The serum and urine parameters were measured, and the tissue sections were histologically stained. The mRNA and protein levels of metabolism-, inflammation-, fibrosis-, and autophagy-related markers were examined by qPCR and western blotting. The microbial composition and metabolites of cecal contents were analyzed through full-length 16S rRNA sequencing and nontargeted metabolomics.

Results

MHD alleviated insulin resistance in DN mice and ameliorated changes in lipid metabolism and inflammation in the liver and fat. In addition, MHD reduced the levels of kidney injury markers in the serum and urine and attenuated inflammation and fibrosis in the kidney. These results were accompanied by enhanced gut barrier function and a markedly altered microbiota composition and metabolites, with an increased abundance of beneficial bacterial species and metabolites. Moreover, MHD itself and the microbial metabolite spermidine reduced podocyte damage by activating autophagy via the PI3K/AKT/mTOR pathway.

Conclusions

MHD potentially ameliorated DN by activating podocyte autophagy via the PI3K/AKT/mTOR pathway and modulating the gut microbiota and its metabolites. Our findings provide a more comprehensive understanding of the mechanism of MHD and the involvement of the gut‒kidney interaction in the progression of DN, laying a theoretical foundation for the clinical application of MHD in DN treatment.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.