{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:31:48Z","timestamp":1792805508019,"version":"4.5.0"},"reference-count":24,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Semyung University Research Grant of 2021.","award":["Semyung University Research Grant of 2021."],"award-info":[{"award-number":["Semyung University Research Grant of 2021."]}],"id":[{"id":"https:\/\/ror.org\/01d100w34","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammation is an important immune response to pathogen invasion, but excessive inflammation leads to tissue injury and even cytokine storm. Therefore, proper response is needed depending on the intensity of the infection. Ras guanine nucleotide releasing protein 3 (RasGRP3) is a regulator of the TLR-mediated response. In low-intensity inflammation, it negatively regulates production of pro-inflammatory cytokines, especially IL-6. Citri Reticulatae Pericarpium, the peel of Citrus reticulata Blanco, is a major medicinal herb in Korean medicine. The present study aims to investigate whether the Citri Reticulatae Pericarpium extract (CRE) has immunomodulatory activity using the Raw264.7 macrophage. Also, we investigated the effect of CRE on RasGRP3 expression. In the present study, CRE reduced IL-6 production in the low-LPS environment (1 ng\/mL) and did not in the high-LPS environment (100 ng\/mL). The suppression of IL-6 production in the low-LPS environment (1 ng\/mL) was abolished after the pretreatment of RasGRP3 siRNA. The reduced RasGRP3 protein content by 100 ng\/mL LPS treatment was increased by CRE treatment. Additionally, nobiletin, a major component of CRE showed a suppressive effect on IL-6 production in the low-LPS environment (1 ng\/mL). The present results suggest that CRE alleviates inflammatory response via activating RasGRP3 expression in low-intensity inflammation.<\/jats:p>","DOI":"10.3390\/ijms241813777","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T09:51:37Z","timestamp":1694080297000},"page":"13777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Citri Reticulatae Pericarpium Limits TLR-4-Triggered Inflammatory Response in Raw264.7 Macrophages by Activating RasGRP3"],"prefix":"10.3390","volume":"24","author":[{"given":"Ji Hye","family":"Lee","sequence":"first","affiliation":[{"name":"School of Korean Medicine, Pusan National University, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yon-Suk","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Biomedical and Health Science, Research Institute of Inflammatory Disease (RID), Konkuk University, Chungju 27478, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5271-0475","authenticated-orcid":false,"given":"Kang Hyun","family":"Leem","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Semyung University, 65 Semyung-ro, Jecheon 27126, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and Metabolic Disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4657","DOI":"10.1038\/ncomms5657","article-title":"RasGRP3 Limits Toll-like Receptor-Triggered Inflammatory Response in Macrophages by Activating Rap1 Small GTPase","volume":"5","author":"Tang","year":"2014","journal-title":"Nat. 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