{"doi":"10.3390/pharmaceutics13050667","title":"Nobiletin Inhibits Inflammatory Reaction in Interleukin-1β-Stimulated Human Periodontal Ligament Cells","abstract":"<jats:p>The immune response in periodontal lesions is involved in the progression of periodontal disease. Therefore, it is important to find a bioactive substance that has anti-inflammatory effects in periodontal lesions. This study aimed to examine if nobiletin, which is found in the peel of citrus fruits, could inhibit inflammatory responses in interleukin (IL)-1β-stimulated human periodontal ligament cells (HPDLCs). The release of cytokines (IL-6, IL-8, CXCL10, CCL20, and CCL2) and matrix metalloproteinases (MMP-1 and MMP-3) was assessed by ELISA. The expression of cell adhesion molecules (ICAM-1and VCAM-1) and the activation of signal transduction pathways (nuclear factor (NF)-κB, mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt)) in HPDLCs were detected by Western blot analysis. Our experiments revealed that nobiletin decreased the expression of inflammatory cytokines, cell adhesion molecules, and MMPs in IL-1β-stimulated HPDLCs. Moreover, we revealed that nobiletin treatment could suppress the activation of the NF-κB, MAPKs, and Akt pathways. These findings indicate that nobiletin could inhibit inflammatory reactions in IL-1β-stimulated HPDLCs by inhibiting multiple signal transduction pathways, including NF-κB, MAPKs, and Akt.</jats:p>","journal":"Pharmaceutics","year":2021,"id":687682,"datarank":0.5333022092234121,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":0.0,"self_endowment_contribution":0.5333022092234121,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1617204,"name":"Ikuko Hosokawa","orcid":null,"position":1,"is_corresponding":false},{"id":1042110,"name":"Kazumi Ozaki","orcid":null,"position":2,"is_corresponding":false},{"id":190618,"name":"Takashi Matsuo","orcid":null,"position":3,"is_corresponding":false},{"id":202748,"name":"Yoshitaka Hosokawa","orcid":"0000-0002-4526-4902","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Nobiletin Inhibits Inflammatory Reaction in Interleukin-1β-Stimulated Human Periodontal Ligament Cells","abstract":"<jats:p>The immune response in periodontal lesions is involved in the progression of periodontal disease. Therefore, it is important to find a bioactive substance that has anti-inflammatory effects in periodontal lesions. This study aimed to examine if nobiletin, which is found in the peel of citrus fruits, could inhibit inflammatory responses in interleukin (IL)-1β-stimulated human periodontal ligament cells (HPDLCs). The release of cytokines (IL-6, IL-8, CXCL10, CCL20, and CCL2) and matrix metalloproteinases (MMP-1 and MMP-3) was assessed by ELISA. The expression of cell adhesion molecules (ICAM-1and VCAM-1) and the activation of signal transduction pathways (nuclear factor (NF)-κB, mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt)) in HPDLCs were detected by Western blot analysis. Our experiments revealed that nobiletin decreased the expression of inflammatory cytokines, cell adhesion molecules, and MMPs in IL-1β-stimulated HPDLCs. Moreover, we revealed that nobiletin treatment could suppress the activation of the NF-κB, MAPKs, and Akt pathways. These findings indicate that nobiletin could inhibit inflammatory reactions in IL-1β-stimulated HPDLCs by inhibiting multiple signal transduction pathways, including NF-κB, MAPKs, and Akt.</jats:p>","is_dataset_classified":null,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34066937","pmcid":"PMC8148442","openalex_id":"https://openalex.org/W3159033506","authors":[],"funders":[{"funder_name":"japan society for the promotion of science","grant_id":"18K09600 and 19K10151","title":null}],"total_grants":1,"fwci":5.534,"citation_percentile":0.95389124,"influential_citations":0,"citation_trend":[{"year":2022,"count":4},{"year":2023,"count":5},{"year":2024,"count":18},{"year":2025,"count":6},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1999-4923/13/5/667/pdf","host_type":"journal"},{"url":"https://www.mdpi.com/1999-4923/13/5/667/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/pharmaceutics13050667","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34066937","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8148442","host_type":"repository"},{"url":"https://doaj.org/article/1129b3075e4b43b38baa1c1c421ad8dd","host_type":"repository"},{"url":"https://tokushima-u.repo.nii.ac.jp/records/2009521","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/pharmaceutics13050667","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8148442","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC8148442?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Bioactive Compounds in Plants","Natural product bioactivities and synthesis","Phytochemical Studies and Bioactivities"],"mesh_terms":[],"keywords":["Nobiletin","Protein kinase B","Signal transduction","Chemistry","Periodontal fiber","Cell biology","Proinflammatory cytokine","Chemokine","Interleukin","NF-κB","Kinase","Inflammation","Cancer research","Cytokine","Immunology","Medicine","Biology","Biochemistry","Dentistry","Periodontal ligament cells","Anti-inflammatory effect"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T22:29:17.424358Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}