ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Renal Pharmacology
This article is part of the Research TopicCardiorenal Metabolic Health and Diabetic Nephropathy: Mechanisms, Biomarkers, and Therapeutic AdvancesView all 7 articles
Huangkui Capsule Mitigates Diabetic Nephropathy via Epigenetic Therapy Effects
Provisionally accepted
- 1China Pharmaceutical University, Nanjing, China
- 2Taizhou University, Taizhou, China
- 3Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
- 4Nanjing University of Chinese Medicine, Nanjing, China
- 5Qilu Medical University, Zibo, China
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Background: Huangkui capsule (HKC), a Chinese herbal medicine derived from Abelmoschus manihot (L.) ethanol extract, has clinical efficacy against diabetic nephropathy (DN). Our research group has actively engaged in exploring the efficacy of HKC in treating DN. The underlying pharmacological mechanisms have progressively become clearer but its epigenetic mechanisms remain unclear. Objective: To elucidate HKC's epigenetic role in the treatment of DN. Methods: Db/db mice (a type 2 diabetes/DN model) were orally administered HKC or vehicle for four weeks. Kidney tissues underwent whole-genome bisulfite sequencing and transcriptome profiling to assess DNA methylation and gene expression patterns. Results: HKC significantly reduced urinary albumin/creatinine ratios, indicating renal protection. Comparative methylation analysis revealed HKC regulated the distribution of 5mC by modulating Tet2 expression, thereby influencing abnormal methylation patterns in DN. Integrative analysis identified 12 DN-associated genes with reversed methylation and expression post-HKC treatment, including Cdk8, Pde4d, Pisd-ps3, and Zc3h7a, which showed high susceptibility to DN progression and HKC intervention. Functional annotation linked these genes to immune regulation, synaptic signaling, and Notch pathways. Conclusion: This study provides the first evidence that HKC ameliorates DN through epigenetic therapy effects, specifically by restoring DNA methylation and transcriptional activity of renal target genes. Further biological experiments to validate these findings are necessary.
Keywords: Abelmoschus manihot (L), diabetic nephropathy, DNA Methylation, Epigenetic pharmacology, Transcriptome sequencing, Whole genome bisulfite sequencing
Received: 25 Dec 2025; Accepted: 11 Feb 2026.
Copyright: © 2026 Yu, Tang, Li, Ge, Wu and Gu. 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: Harvest F Gu
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