{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:02:08Z","timestamp":1780081328065,"version":"3.54.0"},"reference-count":37,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of SMEs and Startups (MSS, Korea)","award":["S3364921"],"award-info":[{"award-number":["S3364921"]}]},{"name":"Ministry of SMEs and Startups (MSS, Korea)","award":["NRF-2022R1A5A8033794"],"award-info":[{"award-number":["NRF-2022R1A5A8033794"]}]},{"name":"Korea government (MSIP)","award":["S3364921"],"award-info":[{"award-number":["S3364921"]}]},{"name":"Korea government (MSIP)","award":["NRF-2022R1A5A8033794"],"award-info":[{"award-number":["NRF-2022R1A5A8033794"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ilex rotunda is a famous medicinal plant with many ethnopharmacological uses. It is traditionally employed for treating inflammation and cardiovascular diseases. In this study, we established green technology to extract the leaves and twigs of I. rotunda. The obtained extracts and their fractions were evaluated for their anti-inflammatory potential. In cytokine assays, the extract, n-hexane (H), methylene chloride (MC), and EtOAc (E) fractions of the twigs of I. rotunda significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)-\u03b1 production in RAW264.7 macrophages. Furthermore, the extract, H, and MC fractions of the leaves of I. rotunda modulated cytokine expression by downregulating LPS-induced NO, IL-6, and TNF-\u03b1 production in RAW264.7 macrophages. Western blotting analysis revealed that the extracts and fractions of the leaves and twigs of I. rotunda inhibited inflammatory cytokines by inactivating nuclear factor kappa B (NF\u03baB) action by reducing the phosphorylation of transcript factor (p65) and nuclear factor-kappa B inhibitor alpha (I\u03baB\u03b1) degradation, or by inactivating mitogen-activated protein kinase (MAPK) through the p38 or ERK signaling pathways via the active ingredients of the leaves and twigs of I. rotunda. Ultra-high-resolution liquid chromatography\u2013Orbitrap mass analysis (UHPLC\u2013ESI-Orbitrap-MS\/MS)-based molecular networking, in cooperation with social open platform-guided isolation and dereplication, led to the identification of metabolites in this plant. Our findings indicate that the leaves and twigs of I. rotunda could be promising candidates for developing therapeutic strategies to treat anti-inflammatory diseases.<\/jats:p>","DOI":"10.3390\/ijms252211965","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T06:41:22Z","timestamp":1730961682000},"page":"11965","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Anti-Inflammatory Effects and Metabolomic Analysis of Ilex Rotunda Extracted by Supercritical Fluid Extraction"],"prefix":"10.3390","volume":"25","author":[{"given":"Duc Dat","family":"Le","sequence":"first","affiliation":[{"name":"College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungangno, Suncheon 57922, Jeonnam, Republic of Korea"},{"name":"Nano Bio Research Center, Jeonnam Bio Foundation, Jangseong 57248, Jeonnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Su","family":"Jang","sequence":"additional","affiliation":[{"name":"Nano Bio Research Center, Jeonnam Bio Foundation, Jangseong 57248, Jeonnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinhquang","family":"Truong","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungangno, Suncheon 57922, Jeonnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thientam","family":"Dinh","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungangno, Suncheon 57922, Jeonnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thinhulinh","family":"Dang","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungangno, Suncheon 57922, Jeonnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soojung","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Natural Cosmetics Science, Graduate School, Sunchon National University, 255 Jun-Gangno, Suncheon 57922, Jeonnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4187-3153","authenticated-orcid":false,"given":"Mina","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungangno, Suncheon 57922, Jeonnam, Republic of Korea"},{"name":"Department of Natural Cosmetics Science, Graduate School, Sunchon National University, 255 Jun-Gangno, Suncheon 57922, Jeonnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"ref_1","unstructured":"Zhonghu, R., Gongheguo, W., Sheng, B.-Y., Dian, W., and Yuan, H. 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