Research progress of traditional Chinese medicine in the prevention and treatment of diabetic nephropathy based on intestinal flora and branched-chain amino acids

doi:10.12092/j.issn.1009-2501.2026.04.012

Abstract

Abstract:

Diabetic nephropathy is characterized by progressive impairment of glomerular filtration and elevated blood glucose levels, ultimately leading to end-stage renal failure. It is one of the primary causes of end-stage renal disease worldwide. The gut microbiota plays a significant role in diabetic nephropathy, and branched-chain amino acids (BCAAs), as metabolites of the gut microbiota, are key regulators of energy support, nutrient sensing, neurotransmitter synthesis, and cell signaling. They serve as critical biomarkers in the development of diabetic nephropathy. Traditional Chinese Medicine (TCM) can prevent and treat diabetic nephropathy by improving gut microbiota function, maintaining its balanced homeostasis, and alleviating BCAAs metabolic disorders. This article primarily explores the roles of gut microbiota and BCAAs in diabetic nephropathy, as well as the research progress of TCM in preventing and treating diabetic nephropathy by regulating gut microbiota and BCAAs metabolism. The aim is to provide new insights with TCM characteristics for the prevention and treatment of diabetic nephropathy.

Key words: intestinal flora, branched-chain amino acids, traditional Chinese medicine, diabetic nephropathy, research progress

CLC Number:

Liya SUN, Jiaxin LI, Guiyan SUN, Zhichao CHEN, Qingfeng WANG, Yufeng YANG, Yan SHI. Research progress of traditional Chinese medicine in the prevention and treatment of diabetic nephropathy based on intestinal flora and branched-chain amino acids[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(4): 527-535.

Figures/Tables 1

References 60

1	He Y, Zhang H, Yang Y, et al. Using metabolomics in diabetes management with traditional Chinese medicine: A review[J]. Am J Chin Med, 2021, 49 (8): 1813- 1837. doi: 10.1142/S0192415X21500865
2	Sun H, Saeedi P, Karuranga S, et al. IDF diabetes atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045[J]. Diabetes Res Clin Pract, 2022, 183, 109119. doi: 10.1016/j.diabres.2021.109119
3	Saeedi P, Salpea P, Karuranga S, et al. Mortality attributable to diabetes in 20-79 years old adults, 2019 estimates: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition[J]. Diabetes Res Clin Pract, 2020, 162, 108086. doi: 10.1016/j.diabres.2020.108086
4	Zhu T, Goodarzi MO. Metabolites linking the gut microbiome with risk for type 2 diabetes[J]. Curr Nutr Rep, 2020, 9 (2): 83- 93. doi: 10.1007/s13668-020-00307-3
5	Sikalidis AK, Maykish A. The gut microbiome and type 2 diabetes mellitus: Discussing a complex relationship[J]. Biomedicines, 2020, 8 (1): 8. doi: 10.3390/biomedicines8010008
6	郭天灏, 程海波. 肠道菌群与氨基酸代谢的相互作用研究进展[J]. 中华中医药杂志, 2023, 38 (10): 4851- 4857.
7	Tao S, Li L, Li L, et al. Understanding the gut-kidney axis among biopsy-proven diabetic nephropathy, type 2 diabetes mellitus and healthy controls: an analysis of the gut microbiota composition[J]. Acta Diabetol, 2019, 56 (5): 581- 592. doi: 10.1007/s00592-019-01316-7
8	Asghari G, Farhadnejad H, Teymoori F, et al. High dietary intake of branched-chain amino acids is associated with an increased risk of insulin resistance in adults[J]. J Diabetes, 2018, 10 (5): 357- 364. doi: 10.1111/1753-0407.12639
9	Anderson JR, Carroll I, Azcarate-Peril MA, et al. A preliminary examination of gut microbiota, sleep, and cognitive flexibility in healthy older adults[J]. Sleep Med, 2017, 38, 104- 107. doi: 10.1016/j.sleep.2017.07.018
10	Cheng G, Liu Y, Guo R, et al. Molecular mechanisms of gut microbiota in diabetic nephropathy[J]. Diabetes Res Clin Pract, 2024, 213, 111726. doi: 10.1016/j.diabres.2024.111726
11	He L, Yang FQ, Tang P, et al. Regulation of the intestinal flora: A potential mechanism of natural medicines in the treatment of type 2 diabetes mellitus[J]. Biomed Pharmacother, 2022, 151, 113091. doi: 10.1016/j.biopha.2022.113091
12	Li Q, Chang Y, Zhang K, et al. Implication of the gut microbiome composition of type 2 diabetic patients from northern China[J]. Sci Rep, 2020, 10 (1): 5450. doi: 10.1038/s41598-020-62224-3
13	Tian E, Wang F, Zhao L, et al. The pathogenic role of intestinal flora metabolites in diabetic nephropathy[J]. Front Physiol, 2023, 14, 1231621. doi: 10.3389/fphys.2023.1231621
14	Du X, Liu J, Xue Y, et al. Alteration of gut microbial profile in patients with diabetic nephropathy[J]. Endocrine, 2021, 73 (1): 71- 84. doi: 10.1007/s12020-021-02721-1
15	Lu J, Chen PP, Zhang JX, et al. GPR43 deficiency protects against podocyte insulin resistance in diabetic nephropathy through the restoration of AMPKα activity[J]. Theranostics, 2021, 11 (10): 4728- 4742. doi: 10.7150/thno.56598
16	Lu CC, Hu ZB, Wang R, et al. Gut microbiota dysbiosis-induced activation of the intrarenal renin-angiotensin system is involved in kidney injuries in rat diabetic nephropathy[J]. Acta Pharmacol Sin, 2020, 41 (8): 1111- 1118. doi: 10.1038/s41401-019-0326-5
17	Fiaccadori E, Cosola C, Sabatino A. Targeting the gut for early diagnosis, prevention, and cure of diabetic kidney disease: Is the phenyl sulfate story another step forward ?[J]. Am J Kidney Dis, 2020, 75 (1): 144- 147. doi: 10.1053/j.ajkd.2019.07.001
18	Wang P, Guo R, Bai X, et al. Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice[J]. Front Endocrinol (Lausanne), 2022, 13, 1034818. doi: 10.3389/fendo.2022.1034818
19	Pengrattanachot N, Thongnak L, Lungkaphin A. The impact of prebiotic fructooligosaccharides on gut dysbiosis and inflammation in obesity and diabetes related kidney disease[J]. Food Funct, 2022, 13 (11): 5925- 5945. doi: 10.1039/D1FO04428A
20	Dai Y, Quan J, Xiong L, et al. Probiotics improve renal function, glucose, lipids, inflammation and oxidative stress in diabetic kidney disease: a systematic review and meta-analysis[J]. Ren Fail, 2022, 44 (1): 862- 880. doi: 10.1080/0886022X.2022.2079522
21	Li YJ, Chen X, Kwan TK, et al. Dietary fiber protects against diabetic nephropathy through short-chain fatty acid-mediated activation of G protein-coupled receptors GPR43 and GPR109A[J]. J Am Soc Nephrol, 2020, 31 (6): 1267- 1281. doi: 10.1681/ASN.2019101029
22	Zhang Y, Zhan L, Zhang L, et al. Branched-chain amino acids in liver diseases: Complexity and controversy[J]. Nutrients, 2024, 16 (12): 1875. doi: 10.3390/nu16121875
23	Kaspy MS, Hannaian SJ, Bell ZW, et al. The effects of branched-chain amino acids on muscle protein synthesis, muscle protein breakdown and associated molecular signalling responses in humans: an update[J]. Nutr Res Rev, 2024, 37 (2): 273- 286. doi: 10.1017/S0954422423000197
24	Jin Q, Ma R. Metabolomics in diabetes and diabetic complications: insights from Epidemiological Studies[J]. Cells, 2021, 10 (11): 2832. doi: 10.3390/cells10112832
25	Deng X, Tang C, Fang T, et al. Disruption of branched-chain amino acid homeostasis promotes the progression of DKD via enhancing inflammation and fibrosis-associated epithelial-mesenchymal transition[J]. Metabolism, 2025, 162, 156037. doi: 10.1016/j.metabol.2024.156037
26	Liu S, Li L, Lou P, et al. Elevated branched-chain α-keto acids exacerbate macrophage oxidative stress and chronic inflammatory damage in type 2 diabetes mellitus[J]. Free Radic Biol Med, 2021, 175, 141- 154. doi: 10.1016/j.freeradbiomed.2021.08.240
27	Zhenyukh O, González-Amor M, Rodrigues-Diez RR, et al. Branched-chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation[J]. J Cell Mol Med, 2018, 22 (10): 4948- 4962. doi: 10.1111/jcmm.13759
28	Wang Y, Li X, Zhang H, et al. Branched-chain amino acid catabolism deficiency accelerates diabetic kidney disease via activating mTORC1 signaling[J]. Kidney Int, 2022, 102 (4): 897- 911.
29	Yu D, Richardson NE, Green CL, et al. The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine[J]. Cell Metab, 2021, 33 (5): 905- 922. doi: 10.1016/j.cmet.2021.03.025
30	Zhao H, Zhang F, Sun D, et al. Branched-chain amino acids exacerbate obesity-related hepatic glucose and lipid metabolic disorders via attenuating Akt2 signaling[J]. Diabetes, 2020, 69 (6): 1164- 1177. doi: 10.2337/db19-0920
31	Dimou A, Tsimihodimos V, Bairaktari E. The critical role of the branched chain amino acids (BCAAs) catabolism-regulating enzymes, branched-chain aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKD), in human pathophysiology[J]. Int J Mol Sci, 2022, 23 (7): 4022. doi: 10.3390/ijms23074022
32	Zhang L, Yue Y, Shi M, et al. Dietary Luffa cylindrica (L. ) Roem promotes branched-chain amino acid catabolism in the circulation system via gut microbiota in diet-induced obese mice[J]. Food Chem, 2020, 320, 126648. doi: 10.1016/j.foodchem.2020.126648
33	Pillai SM, Herzog B, Seebeck P, et al. Differential impact of dietary branched chain and aromatic amino acids on chronic kidney disease progression in rats[J]. Front Physiol, 2019, 10, 1460. doi: 10.3389/fphys.2019.01460
34	Mi N, Zhang XJ, Ding Y, et al. Branched-chain amino acids attenuate early kidney injury in diabetic rats[J]. Biochem Biophys Res Commun, 2015, 466 (2): 240- 246. doi: 10.1016/j.bbrc.2015.09.017
35	Zhou C, Zhang Q, Lu L, et al. Metabolomic profiling of amino acids in human plasma distinguishes diabetic kidney disease from type 2 diabetes mellitus[J]. Front Med (Lausanne), 2021, 8, 765873. doi: 10.3389/fmed.2021.765873
36	Kim JE, Nam H, Park JI, et al. Gut microbial genes and metabolism for methionine and branched-chain amino acids in diabetic nephropathy[J]. Microbiol Spectr, 2023, 11 (2): e234422. doi: 10.1128/spectrum.02344-22
37	Pedersen HK, Gudmundsdottir V, Nielsen HB, et al. Human gut microbes impact host serum metabolome and insulin sensitivity[J]. Nature, 2016, 535 (7612): 376- 381. doi: 10.1038/nature18646
38	Nie Q, Hu J, Gao H, et al. Bioactive dietary fibers selectively promote gut microbiota to exert antidiabetic effects[J]. J Agric Food Chem, 2021, 69 (25): 7000- 7015. doi: 10.1021/acs.jafc.1c01465
39	Li WZ, Stirling K, Yang JJ, et al. Gut microbiota and diabetes: From correlation to causality and mechanism[J]. World J Diabetes, 2020, 11 (7): 293- 308. doi: 10.4239/wjd.v11.i7.293
40	Bloomgarden Z. Diabetes and branched-chain amino acids: What is the link ?[J]. J Diabetes, 2018, 10 (5): 350- 352.
41	Yang J, Dong H, Wang Y, et al. Cordyceps cicadae polysaccharides ameliorated renal interstitial fibrosis in diabetic nephropathy rats by repressing inflammation and modulating gut microbiota dysbiosis[J]. Int J Biol Macromol, 2020, 163, 442- 456. doi: 10.1016/j.ijbiomac.2020.06.153
42	罗欣杰, 杨建华, 胡君萍. 肉苁蓉多糖通过影响肠道菌群抑制Toll样受体4/核因子-κB途径改善小鼠糖尿病肾病[J]. 食品科学, 2024, 45 (21): 185- 193. doi: 10.7506/spkx1002-6630-20240416-154
43	Wang F, Liu C, Ren L, et al. Sanziguben polysaccharides improve diabetic nephropathy in mice by regulating gut microbiota to inhibit the TLR4/NF-κB/NLRP3 signalling pathway[J]. Pharm Biol, 2023, 61 (1): 427- 436. doi: 10.1080/13880209.2023.2174145
44	Zhou K, Zhang J, Liu C, et al. Sanziguben polysaccharides inhibit diabetic nephropathy through NF-κB-mediated anti-inflammation[J]. Nutr Metab (Lond), 2021, 18 (1): 81. doi: 10.1186/s12986-021-00601-z
45	Lyu X, Zhang TT, Ye Z, et al. Astragaloside IV mitigated diabetic nephropathy by restructuring intestinal microflora and ferroptosis[J]. Mol Nutr Food Res, 2024, 68 (6): e2300734. doi: 10.1002/mnfr.202300734
46	于晓依, 常畅, 陈天笑, 等. 王不留行黄酮苷改善糖尿病肾病小鼠肠道菌群紊乱和肾脏脂质沉积的研究[J]. 华西药学杂志, 2024, 39 (1): 36- 42. doi: 10.13375/j.cnki.wcjps.2024.01.008
47	Ju CG, Zhu L, Wang W, et al. Cornus officinalis prior and post-processing: Regulatory effects on intestinal flora of diabetic nephropathy rats[J]. Front Pharmacol, 2022, 13, 1039711. doi: 10.3389/fphar.2022.1039711
48	Han C, Shen Z, Cui T, et al. Yi-Shen-Hua-Shi granule ameliorates diabetic kidney disease by the "gut-kidney axis"[J]. J Ethnopharmacol, 2023, 307, 116257. doi: 10.1016/j.jep.2023.116257
49	姚宇剑, 武素, 倪雅丽, 等. 缩泉益肾方对db-/db-小鼠的肠道菌群影响的研究[J]. 时珍国医国药, 2022, 33 (2): 291- 294. doi: 10.3969/j.issn.1008-0805.2022.02.09
50	姚宇剑, 倪雅丽, 李想, 等. 缩泉益肾方对糖尿病肾病小鼠肠道菌群多样性的影响[J]. 时珍国医国药, 2020, 31 (8): 1846- 1848.
51	杨超茅, 张顺宵, 李园园, 等. 六味地黄汤加减联合氯沙坦钾对糖尿病肾病大鼠ACE1/AngⅡ/AT1R轴及肠道菌群的影响[J]. 中国实验方剂学杂志, 2024, 30 (6): 1- 9. doi: 10.13422/j.cnki.syfjx.20232122
52	Zhang CY, Yue DJ, Wang D, et al. Effects of Bifidobacterium bifidum tetragonum tablets and Jin Gui Ren Qi Pill on intestinal flora and metabolism in patients with diabetic kidney disease[J]. Front Pharmacol, 2024, 15, 1346168. doi: 10.3389/fphar.2024.1346168
53	Rong G, Weng W, Huang J, et al. Artemether alleviates diabetic kidney disease by modulating amino acid metabolism[J]. Biomed Res Int, 2022, 2022, 7339611. doi: 10.1155/2022/7339611
54	Chen R, Liao C, Guo Q, et al. Combined systems pharmacology and fecal metabonomics to study the biomarkers and therapeutic mechanism of type 2 diabetic nephropathy treated with Astragalus and Leech[J]. RSC Adv, 2018, 8 (48): 27448- 27463. doi: 10.1039/C8RA04358B
55	Liu Y, Chen X, Liu Y, et al. Metabolomic study of the protective effect of Gandi capsule for diabetic nephropathy[J]. Chem Biol Interact, 2019, 314, 108815. doi: 10.1016/j.cbi.2019.108815
56	Shi R, Tao Y, Tang H, et al. Abelmoschus manihot ameliorates the levels of circulating metabolites in diabetic nephropathy by modulating gut microbiota in non-obese diabetes mice[J]. Microb Biotechnol, 2023, 16 (4): 813- 826. doi: 10.1111/1751-7915.14200
57	Shao J, Liu Y, Wang H, et al. An integrated fecal microbiome and metabolomics in T2DM rats reveal antidiabetes effects from host-microbial metabolic axis of EtOAc extract from sophora flavescens[J]. Oxid Med Cell Longev, 2020, 2020, 1805418. doi: 10.1155/2020/1805418
58	Yue SJ, Liu J, Wang AT, et al. Berberine alleviates insulin resistance by reducing peripheral branched-chain amino acids[J]. Am J Physiol Endocrinol Metab, 2019, 316 (1): E73- E85. doi: 10.1152/ajpendo.00256.2018
59	Zheng XX, Li DX, Li YT, et al. Mulberry leaf water extract alleviates type 2 diabetes in mice via modulating gut microbiota-host co-metabolism of branched-chain amino acid[J]. Phytother Res, 2023, 37 (8): 3195- 3210.
60	Bao M, Hou K, Xin C, et al. Portulaca oleracea L. extract alleviated type 2 diabetes via modulating the gut microbiota and serum branched-chain amino acid metabolism[J]. Mol Nutr Food Res, 2022, 66 (11): e2101030. doi: 10.1002/mnfr.202101030

[1]	Ying ZHOU, Juntong LIU, Qingfeng WANG, Yufeng YANG, Yan SHI. Research progress on pharmacological mechanism of traditional Chinese medicine targeting type 2 diabetes related pathways [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(4): 500-508.
[2]	Yuanyuan HUANG, Lingzhun WANG. Research progress in the intervention of myocardial fibrosis by regulating signal pathways with traditional Chinese medicine [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(3): 372-381.
[3]	Zhiwei LIU, Shuqing CHEN, Youjun CHEN, Yiming LI, Fangrong YAN, Yang ZHAO, Hua SUN, Haitang XIE, Ling WANG. Current application of P-value: challenges and optimization strategies [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(2): 240-246.
[4]	Yiru WEN, Jinlamu YANG, Ga MEI, Na LI, Yapeng LU, Yan ZHANG, Jieting LIU. Progress in research on macrophage polarization, intestinal flora and their metabolites in organ injury [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(1): 125-132.
[5]	JIANG Jianxiang, DU Peiyan, LIU Yurong, LV Haihong. Correlation study between trimethylamine N-oxide and Hashimoto's thyroiditis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(9): 1208-1214.
[6]	JING Jiawen, MENG Qingbo, BI Zheng, WANG Fanjing, LI Yufan, FANG Zhaohui. Advances in animal models of diabetic erectile dysfunction based on therapeutic approaches [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(9): 1224-1232.
[7]	LYU Chengguo, WU Caiqian, MI Qianrui, ZHANG Guojing, LI Ling, YE Qifa. Apelin: A new target for the prevention and treatment of chronic kidney disease#br# [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(9): 1243-1252.
[8]	XING Ying, ZHENG Rongjiong, JIANG Chunhui, Mayila·kahaer, Muhuyati·wulasihan. Changes of intestinal flora in patients with type 2 diabetes mellitus complicated with coronary heart disease after liraglutide treatment and its correlation with glucose and lipid metabolism indexes [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(8): 1084-1091.
[9]	GAO Zitian, CHEN Yu, HE Haidong, TANG Yuyan. Short-chain fatty acids modulate the role of NLRP3 inflammatory vesicle pathway in CKD and the progress of traditional Chinese medicine intervention [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(6): 812-819.
[10]	ZHANG Yidan, SUN Xinghua, QU Yang, HU Xiaoyang, ZHANG Miao. Research progress on the regulation of PI3K/Akt signaling pathway by active ingredients of traditional Chinese medicine in the treatment of cerebral ischemia-reperfusion injury [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(6): 820-827.
[11]	DING Ding, WU Shengnan, WANG Ancai, WANG Deguo. Research progress on the inhibition of cardiac remodeling by vericiguat [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(6): 858-863.
[12]	ZHANG Mengli, WU Fangfang, TAN Zhien, OU Min, LIU Lingjie, LU Na, QIAO Liya, YANG Xiaonan. Effects of branched-chain and aromatic amino acids on type 2 diabetes mellitus and the progress [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(4): 526-532.
[13]	LIU Yeyuan, QI Yafeng, ZHANG Maofu, LI Xinyu, SHEN Yanyun, LIU Yu, ZHANG Shangzu, LI Yangyang, ZHANG Liying, ZHANG Zhiming. Research progress of traditional Chinese medicine intervention in chemotherapy renal injury [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(4): 556-569.
[14]	WANG Peipei, PAN Linkun, YANG Kui, FENG Dandan. Qingluo Yin inhibits synovial angiogenesis induced by adjuvant in arthritis rats by regulating HIF-1α/VEGF pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(3): 366-373.
[15]	HUANG Shumin, XIE Baocheng, LIU Guohui. Research progress on the mechanism of GLP-1 receptor agonists in the treatment of diabetic nephropathy [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(12): 1701-1710.