{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T15:22:35Z","timestamp":1785943355041,"version":"3.56.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Huangkui capsule (HKC), a Chinese herbal medicine derived from\n                      <jats:italic>Abelmoschus manihot<\/jats:italic>\n                      (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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To elucidate HKC\u2019s epigenetic role in the treatment of DN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Db\/db mice (a type 2 diabetes\/DN model) were orally administered HKC or vehicle for 4\u00a0weeks. Kidney tissues underwent whole-genome bisulfite sequencing and transcriptome profiling to assess DNA methylation and gene expression patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HKC significantly reduced urinary albumin\/creatinine ratios, indicating renal protection. Comparative methylation analysis revealed HKC regulated the distribution of 5\u00a0mC by modulating\n                      <jats:italic>Tet2<\/jats:italic>\n                      expression, thereby influencing abnormal methylation patterns in DN. Integrative analysis identified 12 DN-associated genes with reversed methylation and expression post-HKC treatment, including\n                      <jats:italic>Cdk8, Pde4d, Pisd-ps3<\/jats:italic>\n                      , and\n                      <jats:italic>Zc3h7a<\/jats:italic>\n                      , which showed high susceptibility to DN progression and HKC intervention. Functional annotation linked these genes to immune regulation, synaptic signaling, and Notch pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1775173","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:49:13Z","timestamp":1771922953000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Huangkui capsule mitigates diabetic nephropathy via epigenetic therapy effects"],"prefix":"10.3389","volume":"17","author":[{"given":"Yihong","family":"Yu","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Medicine, China Pharmaceutical University","place":["Nanjing, China"]},{"name":"Laboratory of Minigene Pharmacy, China Pharmaceutical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chemistry and Chemical Engineering, Taizhou University","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Ge","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory of Minigene Pharmacy, China Pharmaceutical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvest F.","family":"Gu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, China Pharmaceutical University","place":["Nanjing, China"]},{"name":"School of Pharmacy, Qilu Medical University","place":["Zibo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"R87","DOI":"10.1186\/gb-2012-13-10-r87","article-title":"methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles","volume":"13","author":"Akalin","year":"2012","journal-title":"Genome Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2490","DOI":"10.2337\/db20-0382","article-title":"Integrative omics analyses reveal epigenetic memory in diabetic renal cells regulating genes associated with kidney dysfunction","volume":"69","author":"Bansal","year":"2020","journal-title":"Diabetes"},{"key":"B3","doi-asserted-by":"publisher","first-page":"4343","DOI":"10.1210\/jc.2017-01922","article-title":"Diabetic microvascular disease: an endocrine society scientific statement","volume":"102","author":"Barrett","year":"2017","journal-title":"J. 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