ORIGINAL RESEARCH article
Front. Med.
Sec. Nephrology
Total flavonoids from Abelmoschus manihot (L.) improve diabetes nephropathy by regulating the gut-kidney axis
Provisionally accepted
- 1Qilu Medical University, Zibo, China
- 2Nanjing Medical University, Nanjing, China
- 3Molecular medicine and surgery, China Pharmaceutical University, Nanjing, China
- 4Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
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Abstract Background: A recent clinical study demonstrated that Huangkui capsule (with its bioactive constituents being total flavones extracted from Abelmoschus manihot (L.), TFA) combined with irbesartan provides effective therapy for type 2 diabetes (T2D) patients with diabetic nephropathy (DN). Objective: To elucidate the therapeutic mechanisms of TFA in DN through modulation of the gut-kidney axis. Methods: The db/db mice were administered TFA, irbesartan, or vehicle. Urinary albumin/creatinine ratio (UACR) was measured by ELISA. Intestinal bacterial composition was analyzed using 16S rRNA sequencing. Serum metabolites were quantified via LC-ESI-MS/MS. Kidney transcriptomics were assessed using Illumina platform-based RNA sequencing. Results: Administration of TFA reduced UACR in db/db mice and significantly altered intestinal flora composition. Specifically, TFA elevated the abundance of Dietzia, Faecium, Streptococcus, and Brautella, while reducing Bacteroidetes, Firmicutes, Enterobacteriaceae, Rikenellaceae, Fusivibrio, and Treponema. In serum metabolomic analysis, TFA increased levels of quercetin 3-glucuronide and n-cinnamyl glycine but decreased cortisol concentrations. Concurrently, renal transcriptomics revealed downregulation of key genes (retnlg, ngp, mpo, camp, ctsg, elane, s100a8, s100a9, trem1, and mmp7), which primarily function in pathways related to neutrophil extracellular trap formation, steroid hormone biosynthesis, and cortisol synthesis/secretion. In contrast, irbesartan treatment did not significantly affect blood pressure or specific renal gene pathways in db/db mice. Conclusions: TFA attenuate diabetic nephropathy (DN) progression through pharmacological mechanisms involving three key axes: (1) modulation of intestinal flora composition, (2) regulation of circulating metabolites, and (3) suppression of renal gene activity pathways. These findings highlight the gut-kidney axis as a central therapeutic target for TFA in DN management.
Keywords: diabetic nephropathy, gut-kidney axis, Irbesartan, total flavones of A. manihot (L.), type 2 diabetes
Received: 27 Aug 2025; Accepted: 11 Dec 2025.
Copyright: © 2025 Yu, Liu, Gu, Tang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Wei Tang
Nan Li
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