{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T10:21:47Z","timestamp":1793701307049,"version":"4.5.1"},"reference-count":77,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274357"],"award-info":[{"award-number":["82274357"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82474501"],"award-info":[{"award-number":["82474501"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC3606200"],"award-info":[{"award-number":["2023YFC3606200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Black sesame pigment (BSP), a key macromolecular component of the traditional food\u2013medicine black sesame, holds potential for improving non-alcoholic fatty liver disease (NAFLD), but its mechanisms remain unclear. We evaluated BSP and fired black sesame pigment (FBSP) in a high-fat diet\/streptozotocin-induced NAFLD mouse model. An integrated multi-omics strategy\u2014encompassing network pharmacology, urinary metabolomics, and 16S rRNA sequencing\u2014was employed to identify potential targets and pathways. Key findings were subsequently validated in a human liver organoid model of NAFLD. FBSP treatment significantly alleviated hepatic steatosis and dysfunction in mice. Multi-omics analysis revealed that FBSP reshaped the gut microbiota (increasing Lactobacillus and Bacteroides) and influenced host glycolysis\/gluconeogenesis metabolism. Both omics predictions converged on the HIF-1 signaling pathway. In human liver organoids, FBSP reduced lipid accumulation and inflammation, and modulated the expression of core HIF-1 pathway genes. This study demonstrates that FBSP ameliorates NAFLD, potentially through a gut\u2013liver axis mechanism that involves microbiota remodeling and subsequent modulation of the hepatic HIF-1 signaling pathway. Our findings position FBSP as a promising food-derived candidate for NAFLD intervention.<\/jats:p>","DOI":"10.3390\/antiox15020177","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T11:09:22Z","timestamp":1769771362000},"page":"177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Black Sesame Pigment Ameliorates Non-Alcoholic Fatty Liver Disease via Modulation of the Gut\u2013Liver Axis and HIF-1 Signaling Pathway"],"prefix":"10.3390","volume":"15","author":[{"given":"Qian","family":"Huang","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1950-2309","authenticated-orcid":false,"given":"Zhuowen","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingpeng","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8426-9060","authenticated-orcid":false,"given":"Wei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4318-5132","authenticated-orcid":false,"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155437","DOI":"10.1016\/j.phymed.2024.155437","article-title":"Rutin ameliorated lipid metabolism dysfunction of diabetic NAFLD via AMPK\/SREBP1 pathway","volume":"126","author":"Liu","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"154457","DOI":"10.1016\/j.metabol.2020.154457","article-title":"Bile acids profile, histopathological indices and genetic variants for non-alcoholic fatty liver disease progression","volume":"116","author":"Nimer","year":"2021","journal-title":"Metabolism"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8495630","DOI":"10.1155\/2016\/8495630","article-title":"Phytochemical Contents and Antioxidant and Antiproliferative Activities of Selected Black and White Sesame Seeds","volume":"2016","author":"Zhou","year":"2016","journal-title":"BioMed Res. 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