{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:57:58Z","timestamp":1785765478789,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Technology R&D Project","doi-asserted-by":"publisher","award":["RS-2025-02219175"],"award-info":[{"award-number":["RS-2025-02219175"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive immunometabolic liver disorder involving lipid dysregulation, inflammation, fibrosis, and extrahepatic immune\u2013neural responses, yet therapies capable of modulating these interconnected processes remain limited. Berberine (BBR), an isoquinoline alkaloid derived from traditional medicinal plants including Coptis chinensis Franch. (Coptidis Rhizoma), has shown metabolic and anti-inflammatory activities; however, its effects on hepatic inflammation and the liver\u2013brain inflammatory axis in MASH remain unclear. Here, network pharmacology and molecular docking were used to predict BBR targets and pathways, followed by in vivo validation in a methionine- and choline-deficient diet-induced mouse model. Liver injury and metabolic alterations were assessed using serum biochemistry and lipid profiles, histological changes by hematoxylin and eosin and Sirius Red staining, and hepatic and hypothalamic inflammation by qRT-PCR, flow cytometry, and Iba-1\/GFAP immunostaining. SREBF1, AKT1, and TGFB1 were identified as core BBR targets, with pathways linked to lipid metabolism, oxidative stress, inflammation, and fibrogenesis. BBR attenuated liver injury, steatosis, steatohepatitis, and fibrosis, suppressed SREBF1-associated lipogenic signaling and fibrogenic gene expression, remodeled circulating monocyte subsets, reduced Kupffer cell accumulation, and inhibited hypothalamic microglial activation. These findings suggest that BBR alleviates MCD-induced steatohepatitis through multi-target regulation of hepatic metabolic dysfunction, immune remodeling, and hypothalamic neuroinflammation.<\/jats:p>","DOI":"10.3390\/ijms27156967","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network Pharmacology and In Vivo Validation Reveal Berberine-Mediated Regulation of the Liver\u2013Brain Inflammatory Axis in MCD-Induced Steatohepatitis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0910-4490","authenticated-orcid":false,"given":"Yeon-Joo","family":"Yoo","sequence":"first","affiliation":[{"name":"Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"},{"name":"Department of Nephrology & Endocrinology, Kyung Hee University Korean Medicine Hospital, Kyung Hee Medical Center, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4438-8093","authenticated-orcid":false,"given":"Ji-Han","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Hoon","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2209-6229","authenticated-orcid":false,"given":"Byung-Cheol","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"},{"name":"Department of Nephrology & Endocrinology, Kyung Hee University Korean Medicine Hospital, Kyung Hee Medical Center, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e65","DOI":"10.12771\/emj.2024.e65","article-title":"Pathogenesis and management of metabolic dysfunction-associated steatohepatitis-related hepatocellular carcinoma: A narrative review","volume":"47","author":"Lee","year":"2024","journal-title":"Ewha Med. 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