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Nonetheless, the potential of OBB in the treatment of hyperuricemic nephropathy (HN) warrants further investigation. Therefore, this investigation focused on elucidating the therapeutic efficacy and underlying mechanism of OBB in counteracting HN. An HN mouse model was established for in\u00a0vivo study, while uric acid (UA)\u2010stimulated human renal tubular epithelial cells (HK\u20102) were used for in\u00a0vitro evaluation. Bioinformatics and molecular docking analyses were also employed. Bioinformatics analysis and molecular docking results underscored the critical involvement of the NLRP3 axis in mediating the protective effects of OBB against HN. In\u00a0vivo, OBB treatment significantly reduced kidney weight and index, improved renal function, and mitigated abnormal histopathological alterations. Moreover, OBB lowered MDA, ROS, IL\u20101\u03b2, IL\u201018, and TNF\u2010\u03b1 levels, along with enhanced SOD and CAT activities, both in\u00a0vitro and in\u00a0vivo. Mechanistically, OBB markedly lowered serum UA levels by increasing the expression of organic cation transporter 1\/2 (OCT1\/2) and organic cation\/carnitine transporter 1\/2 (OCTN1\/2) at both transcriptional and translational levels. Additionally, OBB markedly reduced the expression of Keap1, TXNIP, NLRP3, ASC, Caspase\u20101, and GSDMD\u2010N, while promoting Nrf2 nuclear translocation and enhancing the protein expression of HO\u20101, NQO1, CAT, SOD1, GCLC, and GPX4. Our results for the first time indicated that OBB treatment exerted a significant anti\u2010HN effect. It reduced serum UA level by modulating the OCTs and OCTNs, a mechanism distinct from that of current first\u2010line agents. Additionally, OBB alleviated renal damage through the modulation of the Keap1\/Nrf2\u2010NLRP3 axis.<\/jats:p>","DOI":"10.1002\/ptr.70223","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T14:51:57Z","timestamp":1769179917000},"page":"1334-1353","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Protective Effects of Oxyberberine Against Hyperuricemic Nephropathy: Mechanistic Insights From In Silico, In\u00a0Vitro, and In\u00a0Vivo Studies"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6094-9873","authenticated-orcid":false,"given":"Lieqiang","family":"Xu","sequence":"first","affiliation":[{"name":"College of Bioscience and Bioengineering Jiangxi Agricultural University  Nanchang China"},{"name":"Biotechnological Engineering Center for Pharmaceutical Research and Development Jiangxi Agricultural University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxia","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering Jiangxi Agricultural University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoxiang","family":"Ai","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Institute of Animal Husbandry and Veterinary Science Jiangxi Academy of Agricultural Sciences  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoxing","family":"Dou","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoshu","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7018-3207","authenticated-orcid":false,"given":"Ziren","family":"Su","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7019-1170","authenticated-orcid":false,"given":"Jianhui","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome The Second Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"State Key Laboratory of Dampness Syndrome of Chinese Medicine The Second Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome The Second Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8692-6650","authenticated-orcid":false,"given":"Qingfeng","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome The Second Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucui","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2022.115775"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2022.113215"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603882"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.10.007"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113307"},{"key":"e_1_2_11_7_1","volume-title":"Chinese Pharmacopoeia:2020 Edition. 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