{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T07:13:44Z","timestamp":1771485224277,"version":"3.50.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chronic hepatitis B virus (HBV) infection continues to pose a significant global health burden, and current therapies rarely target the viral covalently closed circular DNA reservoir. Kaempferol (KP), a major flavonoid found in various herbs and plants, exhibits diverse bioactivities, but its potential anti-HBV activity remains unclear. This study aims to investigate the anti-HBV potential of KP and to elucidate its underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The HBV-infected Huh7D\n                      <jats:sup>hNTCP<\/jats:sup>\n                      cell, viral stable transfection cell HepG2.2.15, as well as a hydrodynamic injection-based chronic HBV infection mouse model, were established to evaluate the antiviral effects of KP. The levels of HBV RNAs, DNA and proteins were detected using ELISA, western blot, qPCR, immunofluorescence and immunohistochemistry. To investigate the mechanisms, viral promoter activities were assessed\n                      <jats:italic>via<\/jats:italic>\n                      dual-luciferase reporter assays, and relevant transcription factors were validated through qPCR and western blot analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      KP dose- and time-dependently reduced the levels of viral antigens, RNA, and DNA\n                      <jats:italic>in vitro<\/jats:italic>\n                      , and also significantly lowered viral markers and attenuated HBV-induced hepatic pro-inflammatory cytokines expression\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Furthermore, KP acted in combination with the nucleoside analog entecavir to suppress HBV replication. Mechanistically, KP strongly inhibited the transcriptional activity of the HBV core promoter (Cp), and enhanced the phosphorylation of both extracellular signal-regulated kinase (ERK) and its downstream target forkhead box protein O1 (FOXO1). Importantly, the ERK-specific inhibitor U0126 completely abolished the antiviral effects of KP, confirming that its antiviral activity depended on the ERK\/FOXO1 pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, our results indicate that KP activates ERK-dependent FOXO1 phosphorylation, leading to transcriptional repression of the HBV Cp and thereby suppression of viral replication. These findings identify KP as a potential candidate for developing novel therapeutics against chronic HBV infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1780484","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T06:41:55Z","timestamp":1771483315000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Kaempferol inhibits hepatitis B virus replication via ERK\/FOXO1 pathway-mediated suppression of the viral core promoter"],"prefix":"10.3389","volume":"16","author":[{"given":"Wanyu","family":"Deng","sequence":"first","affiliation":[{"name":"College of Life Science, Shangrao Normal University","place":["Shangrao, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Tibetan Medicine, University of Tibetan Medicine","place":["Lhasa, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haifei","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fu","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Life Science, Shangrao Normal University","place":["Shangrao, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiefeng","family":"Ding","sequence":"additional","affiliation":[{"name":"Shaoxing Women and Children\u2019s Hospital","place":["Shaoxing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Yangzhong People\u2019s Hospital Affiliated to Medical College of Yangzhou University","place":["Yangzhong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]},{"name":"State Key Laboratory of Organ Failure Research, Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Guangdong Institute of Hepatology, Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Qin","sequence":"additional","affiliation":[{"name":"Shaoxing Women and Children\u2019s Hospital","place":["Shaoxing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Dou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/1387665","article-title":"Hepatoprotective effect of kaempferol: A review of the dietary sources, bioavailability, mechanisms of action, and safety","volume":"2023","author":"Alkandahri","year":"2023","journal-title":"Adv. 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