{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:05:15Z","timestamp":1791165915486,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173978"],"award-info":[{"award-number":["82173978"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bile\u2010Processed Coptidis Rhizoma (BPCR), which is processed with Coptidis Rhizoma (CR) and pig bile (PB), exhibits stronger efficacy in treating type 2 diabetes mellitus (T2DM) than CR alone. However, the impact of PB processing on the pharmacokinetics of active components in CR is still unclear. This study aims to investigate the pharmacokinetics and tissue distribution of BPCR in T2DM rats and clarify the enhancement mechanisms of PB processing. This study employed ultrahigh\u2010performance liquid chromatography quadrupole\u2010orbitrap high\u2010resolution mass spectrometry (UHPLC\u2010Q\u2010Orbitrap HRMS) to identify chemical components in the serum of rats after oral BPCR administration. A T2DM rat model was induced using a high\u2010fat diet and streptozotocin. T2DM rats received 10\u00a0g\/kg of CR, fried Coptidis Rhizoma (FCR), or BPCR, whereas the control group received the same dose of BPCR. Berberine levels in plasma and tissues were measured using ultrahigh\u2010performance liquid chromatography\u2010tandem mass spectrometry (UHPLC\u2010QQQ\u2010MS)\/MS. Serum pharmacochemical analysis after oral BPCR administration identified one parent compound, berberine, and four metabolites. Pharmacokinetic studies revealed significant differences in maximum plasma concentration (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ), time to peak concentration (\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ), and HL_Lambda_z (h) for BPCR compared to FCR and CR in T2DM rats (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.05). In T2DM rats, significant differences in area under the concentration\u2010time curve (AUClast) and clearance rate\/bioavailability (Cl_F_obs) were observed compared to the normal group (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.05). The concentration of berberine in various tissues after BPCR administration was consistently higher than that after FCR and CR. Additionally, T2DM rats showed significantly increased berberine concentrations after BPCR administration compared to the control group (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.05). PB processing significantly influences the pharmacokinetics and tissue distribution of berberine in T2DM rats.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202502803","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T17:54:41Z","timestamp":1765907681000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative Pharmacokinetics and Tissue Distribution of Berberine From Bile\u2010Processed Coptidis Rhizoma in Type 2 Diabetic Rats"],"prefix":"10.1002","volume":"23","author":[{"given":"Ying","family":"Zhu","sequence":"first","affiliation":[{"name":"College of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6071-051X","authenticated-orcid":false,"given":"Qinwan","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Modern Chinese Medicine Industry Chengdu University of Traditional Chinese Medicine  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Ethnic Medicine Chengdu University of Traditional Chinese Medicine  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109119"},{"key":"e_1_2_13_3_1","first-page":"2254","article-title":"[Berberine Regulates Type 2 Diabetes Mellitus Related With Insulin Resistance]","volume":"42","author":"Li C.","year":"2017","journal-title":"Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc23-S002"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.958218"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13099-021-00446-0"},{"key":"e_1_2_13_7_1","first-page":"4729","article-title":"Huanglian Wendan Decoction Regulates NLRP3 Inflammasome to Resist Atherosclerosis Mechanism","volume":"42","author":"Yang J.","year":"2022","journal-title":"Chinese Journal of Gerontology"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2018.09.228"},{"key":"e_1_2_13_9_1","first-page":"637","article-title":"[Medicinal Research Progress on Pig Bile and Overview of Its Quality Control]","volume":"43","author":"Shi Y.","year":"2018","journal-title":"Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.11.017"},{"key":"e_1_2_13_11_1","first-page":"2638","article-title":"Differences in Effective Mechanisms of Coptidis Rhizoma and Bile Processed Coptidis Rhizoma on Heat Syndrome Based on Urinary Metabonomics","volume":"41","author":"Wang J.","year":"2016","journal-title":"China Journal of Chinese Materia Medica"},{"key":"e_1_2_13_12_1","first-page":"140","article-title":"Exploration of Material Basis of \"Clearing Excessive Fire of Liver\u2010Gallbladder\" of Bile\u2010Processed Coptidis Rhizoma Based on UPLC\u2010Q\u2010TOF\/MS Metabolomics and Molecular Docking Technology","volume":"29","author":"Dong Z.","year":"2023","journal-title":"Chinese Journal of Experimental Traditional Medical 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of Pharmacokinetics of Berberine in Jiaotai Pill Aqueous Extract and Its Monomer in Rats","volume":"44","author":"Yang X.","year":"2022","journal-title":"Chinese Journal of Traditional Chinese Medicine"},{"key":"e_1_2_13_38_1","first-page":"127","article-title":"[Alteration of Related Transporters and Its Application Significance in Common Intestinal Disease, Liver Disease, Renal Disease and Diabetes]","volume":"50","author":"Wang L.","year":"2015","journal-title":"Yao Xue Xue Bao = Acta Pharmaceutica Sinica"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2022.08.005"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.07.011"}],"container-title":["Chemistry &amp; 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