{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T22:15:57Z","timestamp":1778710557354,"version":"3.51.4"},"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Chronic oral inflammation and biofilm-mediated infections drive diseases such as dental caries and periodontitis. This study investigated the anti-inflammatory and antibacterial potential of an ethanol extract from<jats:italic>Astilbe chinensis<\/jats:italic>inflorescence (GA-13-6) as a prominent candidate for natural complex substances (NCS) with therapeutic potential. In LPS-stimulated RAW 264.7 macrophages, GA-13-6 significantly suppressed proinflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor (TNF), and nitric oxide (NO), surpassing purified astilbin, a known bioactive compound found in<jats:italic>A<\/jats:italic>.<jats:italic>chinensis<\/jats:italic>. Furthermore, GA-13-6 downregulated the expression of cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS), indicating an inhibitory effect on the inflammatory cascade. Remarkably, GA-13-6 exhibited selective antibacterial activity against<jats:italic>Streptococcus mutans<\/jats:italic>,<jats:italic>Streptococcus sanguinis<\/jats:italic>, and<jats:italic>Porphyromonas gingivalis<\/jats:italic>, key players in dental caries and periodontitis, respectively. These findings suggest that complex GA-13-6 holds the potential for the treatment or prevention of periodontal and dental diseases, as well as various other inflammation-related conditions, while averting the induction of antibiotic resistance.<\/jats:p>","DOI":"10.1371\/journal.pone.0306543","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T17:23:43Z","timestamp":1720027423000},"page":"e0306543","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ethanol extract from Astilbe chinensis inflorescence suppresses inflammation in macrophages and growth of oral pathogenic bacteria"],"prefix":"10.1371","volume":"19","author":[{"given":"Jong Min","family":"Han","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ina","family":"Yun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung Mi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye-Sung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Youn","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wonsik","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2498-7546","authenticated-orcid":true,"given":"Seong Su","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4973-6823","authenticated-orcid":true,"given":"Inseong","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"issue":"4","key":"pone.0306543.ref001","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.adaj.2015.11.008","article-title":"Clinical practice guidelines for oral management of Sj\u00f6gren disease: Dental caries prevention","volume":"147","author":"DT Zero","year":"2016","journal-title":"J Am Dent Assoc"},{"key":"pone.0306543.ref002","doi-asserted-by":"crossref","first-page":"17038","DOI":"10.1038\/nrdp.2017.38","article-title":"Periodontal diseases","volume":"3","author":"DF Kinane","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"3","key":"pone.0306543.ref003","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1128\/MMBR.66.3.486-505.2002","article-title":"Communication among oral bacteria","volume":"66","author":"PE Kolenbrander","year":"2002","journal-title":"Microbiol Mol Biol Rev"},{"key":"pone.0306543.ref004","doi-asserted-by":"crossref","first-page":"986264","DOI":"10.1155\/2014\/986264","article-title":"LPS from P. gingivalis and hypoxia increases oxidative stress in periodontal ligament fibroblasts and contributes to periodontitis","volume":"2014","author":"L Golz","year":"2014","journal-title":"Mediators Inflamm"},{"issue":"3","key":"pone.0306543.ref005","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1177\/0022034510379602","article-title":"The role of bacteria in the caries process: ecological perspectives","volume":"90","author":"N Takahashi","year":"2011","journal-title":"J Dent Res"},{"issue":"7","key":"pone.0306543.ref006","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1039\/C9MD00015A","article-title":"Targeting S. mutans biofilms: a perspective on preventing dental caries","volume":"10","author":"AM Scharnow","year":"2019","journal-title":"Medchemcomm"},{"issue":"5","key":"pone.0306543.ref007","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1007\/s13238-018-0548-1","article-title":"Oral microbiomes: more and more importance in oral cavity and whole body","volume":"9","author":"L Gao","year":"2018","journal-title":"Protein Cell"},{"issue":"6","key":"pone.0306543.ref008","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1111\/mmi.12625","article-title":"The relationship of the lipoprotein SsaB, manganese and superoxide dismutase in Streptococcus sanguinis virulence for endocarditis","volume":"92","author":"KE Crump","year":"2014","journal-title":"Mol Microbiol"},{"issue":"5","key":"pone.0306543.ref009","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.autrev.2017.03.009","article-title":"Streptococcus mutans antigen I\/II and autoimmunity in cardiovascular diseases","volume":"16","author":"A. Lucchese","year":"2017","journal-title":"Autoimmun Rev"},{"key":"pone.0306543.ref010","doi-asserted-by":"crossref","first-page":"609614","DOI":"10.3389\/fphys.2020.609614","article-title":"Inflammation in Periodontal Disease: Possible Link to Vascular Disease","volume":"11","author":"O Paul","year":"2020","journal-title":"Front Physiol"},{"issue":"1","key":"pone.0306543.ref011","doi-asserted-by":"crossref","first-page":"eaau3333","DOI":"10.1126\/sciadv.aau3333","article-title":"Porphyromonas gingivalis in Alzheimer\u2019s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors","volume":"5","author":"SS Dominy","year":"2019","journal-title":"Sci Adv"},{"issue":"1","key":"pone.0306543.ref012","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3233\/JAD-200064","article-title":"Clinical and Bacterial Markers of Periodontitis and Their Association with Incident All-Cause and Alzheimer\u2019s Disease Dementia in a Large National Survey","volume":"75","author":"MA Beydoun","year":"2020","journal-title":"J Alzheimers Dis"},{"key":"pone.0306543.ref013","first-page":"1","article-title":"Porphyromonas gingivalis Outer Membrane Vesicles as the Major Driver of and Explanation for Neuropathogenesis, the Cholinergic Hypothesis, Iron Dyshomeostasis, and Salivary Lactoferrin in Alzheimer\u2019s Disease","author":"PL Nara","year":"2021","journal-title":"J Alzheimers Dis"},{"key":"pone.0306543.ref014","doi-asserted-by":"crossref","first-page":"585917","DOI":"10.3389\/fcimb.2020.585917","article-title":"The Role of Porphyromonas gingivalis Outer Membrane Vesicles in Periodontal Disease and Related Systemic Diseases","volume":"10","author":"Z Zhang","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"issue":"35","key":"pone.0306543.ref015","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.2174\/1381612828666220920114723","article-title":"Current Issues and Perspectives in Antimicrobials use in Dental Practice","volume":"28","author":"L Santacroce","year":"2022","journal-title":"Curr Pharm Des"},{"issue":"1","key":"pone.0306543.ref016","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12941-023-00585-z","article-title":"The oral microbiota is a reservoir for antimicrobial resistance: resistome and phenotypic resistance characteristics of oral biofilm in health, caries, and periodontitis","volume":"22","author":"AC Anderson","year":"2023","journal-title":"Ann Clin Microbiol Antimicrob"},{"issue":"2","key":"pone.0306543.ref017","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41579-023-00963-6","article-title":"The oral microbiome: diversity, biogeography and human health","volume":"22","author":"JL Baker","year":"2024","journal-title":"Nat Rev Microbiol"},{"key":"pone.0306543.ref018","doi-asserted-by":"crossref","first-page":"127548","DOI":"10.1016\/j.micres.2023.127548","article-title":"Inhibition of pathogenic microbes in oral infectious diseases by natural products: Sources, mechanisms, and challenges","volume":"279","author":"X Cao","year":"2024","journal-title":"Microbiol Res"},{"issue":"2","key":"pone.0306543.ref019","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1080\/10286020.2010.546355","article-title":"Chemical constituents from Astilbe chinensis","volume":"13","author":"Y Xue","year":"2011","journal-title":"J Asian Nat Prod Res"},{"key":"pone.0306543.ref020","doi-asserted-by":"crossref","first-page":"1347612","DOI":"10.1155\/2018\/1347612","article-title":"Antiobesity Effect of Astilbe chinensis Franch. et Savet. Extract through Regulation of Adipogenesis and AMP-Activated Protein Kinase Pathways in 3T3-L1 Adipocyte and High-Fat Diet-Induced C57BL\/6N Obese Mice","volume":"2018","author":"XH Zhang","year":"2018","journal-title":"Evid Based Complement Alternat Med"},{"issue":"2","key":"pone.0306543.ref021","first-page":"261","article-title":"Screening of Korean Medicinal Plant Extracts for \u03b1-Glucosidase Inhibitory Activities","volume":"10","author":"S Sancheti","year":"2011","journal-title":"Iran J Pharm Res"},{"issue":"2","key":"pone.0306543.ref022","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.intimp.2010.12.002","article-title":"Effects of astilbic acid on airway hyperresponsiveness and inflammation in a mouse model of allergic asthma","volume":"11","author":"JE Yuk","year":"2011","journal-title":"Int Immunopharmacol"},{"key":"pone.0306543.ref023","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.3389\/fphar.2018.01187","article-title":"Astilbin Inhibits High Glucose-Induced Inflammation and Extracellular Matrix Accumulation by Suppressing the TLR4\/MyD88\/NF-\u03baB Pathway in Rat Glomerular Mesangial Cells","volume":"9","author":"F Chen","year":"2018","journal-title":"Front Pharmacol"},{"issue":"8","key":"pone.0306543.ref024","first-page":"606","article-title":"HPLC determination of bergenin in Astilbe chinensis (Maxim.) Franch. et Sav. and Bergenia purpurascens (Hook. F. et Thoms.) Engl","volume":"23","author":"WD Chen","year":"1988","journal-title":"Yao Xue Xue Bao"},{"issue":"1","key":"pone.0306543.ref025","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1248\/bpb.28.24","article-title":"Antiinflammatory activity of astilbic acid from Astilbe chinensis","volume":"28","author":"TC Moon","year":"2005","journal-title":"Biol Pharm Bull"},{"issue":"3","key":"pone.0306543.ref026","first-page":"3789","article-title":"Astilbin emulsion improves guinea pig lesions in a psoriasis-like model by suppressing IL-6 and IL-22 via p38 MAPK","volume":"17","author":"J Yu","year":"2018","journal-title":"Mol Med Rep"},{"issue":"22","key":"pone.0306543.ref027","doi-asserted-by":"crossref","first-page":"13104","DOI":"10.1111\/jcmm.15915","article-title":"Astilbin prevents osteoarthritis development through the TLR4\/MD-2 pathway","volume":"24","author":"S Sun","year":"2020","journal-title":"J Cell Mol Med"},{"issue":"1","key":"pone.0306543.ref028","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1186\/s12906-020-03073-5","article-title":"Astilbe chinensis ethanol extract suppresses inflammation in macrophages via NF-\u03baB pathway","volume":"20","author":"TY Gil","year":"2020","journal-title":"BMC Complement Med Ther"},{"issue":"12","key":"pone.0306543.ref029","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/ptr.1599","article-title":"Effect of the rhizomes of Astilbe chinensis on UVB-induced inflammatory response","volume":"18","author":"M Na","year":"2004","journal-title":"Phytother Res"},{"issue":"11","key":"pone.0306543.ref030","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1002\/ijc.23161","article-title":"Targeting NOX, INOS and COX-2 in inflammatory cells: Chemoprevention using food phytochemicals","volume":"121","author":"A Murakami","year":"2007","journal-title":"Int J Cancer"},{"key":"pone.0306543.ref031","doi-asserted-by":"crossref","first-page":"113790","DOI":"10.1016\/j.phytochem.2023.113790","article-title":"Natural complex substances: From molecules to the molecular complexes. Analytical and technological advances for their definition and differentiation from the corresponding synthetic substances","volume":"215","author":"L Mattoli","year":"2023","journal-title":"Phytochemistry"},{"key":"pone.0306543.ref032","unstructured":"EFEO\/IFRA. Guidelines on Substance Identification and Sameness of Natural Complex Substances (NCS) under REACH and CLP. 2015:3\u20136."},{"issue":"2","key":"pone.0306543.ref033","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jep.2008.07.007","article-title":"Immunomodulatory and antitumor activity of triterpenoid fractions from the rhizomes of Astilbe chinensis","volume":"119","author":"J Tu","year":"2008","journal-title":"J Ethnopharmacol"},{"issue":"4","key":"pone.0306543.ref034","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/j.bmc.2005.09.043","article-title":"Induction of apoptosis in HeLa cells by 3\u03b2-hydroxy-12-oleanen-27-oic acid from the rhizomes of Astilbe chinensis","volume":"14","author":"HX Sun","year":"2006","journal-title":"Bioorg Med Chem"},{"issue":"2\u20133","key":"pone.0306543.ref035","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jep.2003.10.003","article-title":"Cytotoxic oleanane triterpenoids from the rhizomes of Astilbe chinensis (Maxim.) Franch. et Savat","volume":"90","author":"HX Sun","year":"2004","journal-title":"J Ethnopharmacol"},{"issue":"7","key":"pone.0306543.ref036","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1021\/np900028v","article-title":"Cytotoxic triterpenoids from the rhizomes of Astilbe chinensis","volume":"72","author":"XF Cai","year":"2009","journal-title":"J Nat Prod"},{"issue":"8","key":"pone.0306543.ref037","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1002\/cbdv.200800187","article-title":"Immunomodulatory activity of 3\u03b2,6\u03b2-dihydroxyolean-12-en-27-oic acid in tumor-bearing mice","volume":"6","author":"W Deng","year":"2009","journal-title":"Chem Biodivers"},{"key":"pone.0306543.ref038","doi-asserted-by":"crossref","first-page":"3835021","DOI":"10.1155\/2018\/3835021","article-title":"Astilbe chinensis Modulates Platelet Function via Impaired MAPK and PLC\u03b32 Expression","volume":"2018","author":"BR Jeon","year":"2018","journal-title":"Evid Based Complement Alternat Med"},{"issue":"1","key":"pone.0306543.ref039","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/s12035-013-8425-7","article-title":"Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway","volume":"48","author":"K Lucas","year":"2013","journal-title":"Mol Neurobiol"},{"issue":"16","key":"pone.0306543.ref040","doi-asserted-by":"crossref","first-page":"10689","DOI":"10.1074\/jbc.274.16.10689","article-title":"Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction","volume":"274","author":"JC Chow","year":"1999","journal-title":"J Biol Chem"},{"issue":"1","key":"pone.0306543.ref041","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1172\/JCI11830","article-title":"NF-\u03baB: a key role in inflammatory diseases","volume":"107","author":"PP Tak","year":"2001","journal-title":"J Clin Invest"},{"issue":"7","key":"pone.0306543.ref042","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.lfs.2005.04.051","article-title":"Inhibitory effect of naringin on lipopolysaccharide (LPS)-induced endotoxin shock in mice and nitric oxide production in RAW 264.7 macrophages","volume":"78","author":"S Kanno","year":"2006","journal-title":"Life Sci"},{"key":"pone.0306543.ref043","doi-asserted-by":"crossref","first-page":"610813","DOI":"10.1155\/2015\/610813","article-title":"Interrelation of oxidative stress and inflammation in neurodegenerative disease: role of TNF","volume":"2015","author":"R Fischer","year":"2015","journal-title":"Oxid Med Cell Longev"},{"issue":"10","key":"pone.0306543.ref044","doi-asserted-by":"crossref","first-page":"a016295","DOI":"10.1101\/cshperspect.a016295","article-title":"IL-6 in inflammation, immunity, and disease","volume":"6","author":"T Tanaka","year":"2014","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"6","key":"pone.0306543.ref045","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1007\/s10787-007-0013-x","article-title":"Role of nitric oxide in inflammatory diseases","volume":"15","author":"JN Sharma","year":"2007","journal-title":"Inflammopharmacology"},{"issue":"3","key":"pone.0306543.ref046","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1182\/blood.V86.3.1184.1184","article-title":"Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): analysis of iNOS mRNA, iNOS protein, biopterin, and nitric oxide production by blood monocytes and peritoneal macrophages","volume":"86","author":"JB Weinberg","year":"1995","journal-title":"Blood"},{"issue":"1","key":"pone.0306543.ref047","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/j.1365-2125.2007.02990.x","article-title":"Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism","volume":"65","author":"E Schwedhelm","year":"2008","journal-title":"Br J Clin Pharmacol"},{"issue":"15","key":"pone.0306543.ref048","doi-asserted-by":"crossref","first-page":"7240","DOI":"10.1073\/pnas.90.15.7240","article-title":"Nitric oxide activates cyclooxygenase enzymes","volume":"90","author":"D Salvemini","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6","key":"pone.0306543.ref049","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1189\/jlb.71.6.1005","article-title":"Regulation of cyclooxygenase-2 by nitric oxide in activated hepatic macrophages during acute endotoxemia","volume":"71","author":"N Ahmad","year":"2002","journal-title":"J Leukoc Biol"},{"key":"pone.0306543.ref050","doi-asserted-by":"crossref","first-page":"101933","DOI":"10.1016\/j.redox.2021.101933","article-title":"Network analysis of nitrate-sensitive oral microbiome reveals interactions with cognitive function and cardiovascular health across dietary interventions","volume":"41","author":"A Vanhatalo","year":"2021","journal-title":"Redox Biol"},{"issue":"7","key":"pone.0306543.ref051","doi-asserted-by":"crossref","first-page":"R473","DOI":"10.1152\/ajpregu.00355.2012","article-title":"Reciprocal regulation of the nitric oxide and cyclooxygenase pathway in pathophysiology: relevance and clinical implications","volume":"304","author":"D Salvemini","year":"2013","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"pone.0306543.ref052","doi-asserted-by":"crossref","first-page":"8246420","DOI":"10.1155\/2017\/8246420","article-title":"Astilbin from Smilax glabra Roxb. Attenuates Inflammatory Responses in Complete Freund\u2019s Adjuvant-Induced Arthritis Rats","volume":"2017","author":"L Dong","year":"2017","journal-title":"Evid Based Complement Alternat Med"},{"issue":"1","key":"pone.0306543.ref053","doi-asserted-by":"crossref","first-page":"625","DOI":"10.3390\/molecules20010625","article-title":"Optimization of astilbin extraction from the rhizome of Smilax glabra, and evaluation of its anti-inflammatory effect and probable underlying mechanism in lipopolysaccharide-induced RAW264.7 macrophages","volume":"20","author":"CL Lu","year":"2015","journal-title":"Molecules"},{"issue":"4","key":"pone.0306543.ref054","first-page":"268","article-title":"An in vitro inhibitory effect on RAW 264.7 cells by anti-inflammatory compounds from Smilax corbularia Kunth","volume":"30","author":"S Ruangnoo","year":"2012","journal-title":"Asian Pac J Allergy Immunol"},{"key":"pone.0306543.ref055","doi-asserted-by":"crossref","first-page":"104894","DOI":"10.1016\/j.phrs.2020.104894","article-title":"Astilbin: A Promising Unexplored Compound with Multidimensional Medicinal and Health Benefits","volume":"158","author":"A Sharma","year":"2020","journal-title":"Pharmacol Res"},{"key":"pone.0306543.ref056","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.intimp.2015.12.035","article-title":"Astilbin inhibits Th17 cell differentiation and ameliorates imiquimod-induced psoriasis-like skin lesions in BALB\/c mice via Jak3\/Stat3 signaling pathway","volume":"32","author":"TT Di","year":"2016","journal-title":"Int Immunopharmacol"},{"issue":"4","key":"pone.0306543.ref057","doi-asserted-by":"crossref","first-page":"e0124002","DOI":"10.1371\/journal.pone.0124002","article-title":"Decrease of Functional Activated T and B Cells and Treatment of Glomerulonephitis in Lupus-Prone Mice Using a Natural Flavonoid Astilbin","volume":"10","author":"L Guo","year":"2015","journal-title":"PLoS ONE"},{"issue":"9","key":"pone.0306543.ref058","doi-asserted-by":"crossref","first-page":"4562","DOI":"10.1021\/jf2002969","article-title":"Isolation and characterization of two flavonoids, engeletin and astilbin, from the leaves of Engelhardia roxburghiana and their potential anti-inflammatory properties","volume":"59","author":"H Huang","year":"2011","journal-title":"J Agric Food Chem"},{"issue":"4","key":"pone.0306543.ref059","first-page":"3078","article-title":"Astilbin-induced inhibition of the PI3K\/AKT signaling pathway decelerates the progression of osteoarthritis","volume":"20","author":"C Chen","year":"2020","journal-title":"Exp Ther Med"},{"issue":"1","key":"pone.0306543.ref060","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/prd.12344","article-title":"Clinical and public health implications of periodontal and systemic diseases: An overview","volume":"83","author":"RJ Genco","year":"2020","journal-title":"Periodontol 2000"},{"key":"pone.0306543.ref061","first-page":"53","article-title":"Porphyromonas gingivalis: An Overview of Periodontopathic Pathogen below the Gum Line","volume":"7","author":"KY How","year":"2016","journal-title":"Front Microbiol"},{"issue":"9","key":"pone.0306543.ref062","doi-asserted-by":"crossref","first-page":"5367","DOI":"10.1128\/IAI.73.9.5367-5378.2005","article-title":"Porphyromonas gingivalis fimbria-dependent activation of inflammatory genes in human aortic endothelial cells","volume":"73","author":"HH Chou","year":"2005","journal-title":"Infect Immun"},{"issue":"1","key":"pone.0306543.ref063","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1128\/IAI.70.1.257-267.2002","article-title":"Fimbria-dependent activation of cell adhesion molecule expression in Porphyromonas gingivalis-infected endothelial cells","volume":"70","author":"M Khlgatian","year":"2002","journal-title":"Infect Immun"},{"issue":"5","key":"pone.0306543.ref064","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1111\/j.1462-5822.2005.00661.x","article-title":"Fimbria-dependent activation of pro-inflammatory molecules in Porphyromonas gingivalis infected human aortic endothelial cells","volume":"8","author":"Y Takahashi","year":"2006","journal-title":"Cell Microbiol"},{"issue":"5","key":"pone.0306543.ref065","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/j.1365-2796.2007.01917.x","article-title":"The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation","volume":"263","author":"T Bengtsson","year":"2008","journal-title":"J Intern Med"},{"issue":"12","key":"pone.0306543.ref066","doi-asserted-by":"crossref","first-page":"8050","DOI":"10.1128\/IAI.73.12.8050-8059.2005","article-title":"Sensitization of human aortic endothelial cells to lipopolysaccharide via regulation of Toll-like receptor 4 by bacterial fimbria-dependent invasion","volume":"73","author":"H Yumoto","year":"2005","journal-title":"Infect Immun"},{"issue":"2","key":"pone.0306543.ref067","doi-asserted-by":"crossref","first-page":"433","DOI":"10.2337\/diacare.28.2.433","article-title":"Relationship of periodontal bacterium genotypic variations with periodontitis in type 2 diabetic patients","volume":"28","author":"M Ojima","year":"2005","journal-title":"Diabetes Care"},{"issue":"7","key":"pone.0306543.ref068","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1177\/0022034520911037","article-title":"Porphyromonas gingivalis Induces Insulin Resistance by Increasing BCAA Levels in Mice","volume":"99","author":"J Tian","year":"2020","journal-title":"J Dent Res"},{"issue":"5","key":"pone.0306543.ref069","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1097\/BOR.0000000000000638","article-title":"Porphyromonas gingivalis and rheumatoid arthritis","volume":"31","author":"C Perricone","year":"2019","journal-title":"Curr Opin Rheumatol"},{"issue":"1","key":"pone.0306543.ref070","doi-asserted-by":"crossref","first-page":"1563405","DOI":"10.1080\/20002297.2018.1563405","article-title":"Assessing the role of Porphyromonas gingivalis in periodontitis to determine a causative relationship with Alzheimer\u2019s disease","volume":"11","author":"SK Singhrao","year":"2019","journal-title":"J Oral Microbiol"},{"issue":"1","key":"pone.0306543.ref071","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3233\/JAD-140315","article-title":"Active invasion of Porphyromonas gingivalis and infection-induced complement activation in ApoE-\/- mice brains","volume":"43","author":"S Poole","year":"2015","journal-title":"J Alzheimers Dis"},{"issue":"1","key":"pone.0306543.ref072","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1600-0757.2010.00377.x","article-title":"Dichotomy of gingipains action as virulence factors: from cleaving substrates with the precision of a surgeon\u2019s knife to a meat chopper-like brutal degradation of proteins","volume":"54","author":"Y Guo","year":"2010","journal-title":"Periodontol 2000"},{"key":"pone.0306543.ref073","doi-asserted-by":"crossref","first-page":"646259","DOI":"10.3389\/fimmu.2021.646259","article-title":"Characterization of Human Genes Modulated by Porphyromonas gingivalis Highlights the Ribosome, Hypothalamus, and Cholinergic Neurons","volume":"12","author":"S Patel","year":"2021","journal-title":"Front Immunol"},{"issue":"7","key":"pone.0306543.ref074","doi-asserted-by":"crossref","first-page":"166836","DOI":"10.1016\/j.jmb.2021.166836","article-title":"Molecular Strategies Underlying Porphyromonas gingivalis Virulence","volume":"433","author":"I Lunar Silva","year":"2021","journal-title":"J Mol Biol"},{"issue":"5","key":"pone.0306543.ref075","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/omi.12134","article-title":"Spheres of influence: Porphyromonas gingivalis outer membrane vesicles","volume":"31","author":"MJ Gui","year":"2016","journal-title":"Mol Oral Microbiol"},{"issue":"1","key":"pone.0306543.ref076","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/ptr.6208","article-title":"Antibacterial activity of flavonoids and their structure-activity relationship: An update review","volume":"33","author":"F Farhadi","year":"2019","journal-title":"Phytother Res"},{"issue":"1","key":"pone.0306543.ref077","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s11101-018-9591-z","article-title":"Comprehensive review of antimicrobial activities of plant flavonoids","volume":"18","author":"I G\u00f3rniak","year":"2019","journal-title":"Phytochem Rev"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0306543","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T11:23:22Z","timestamp":1732361002000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0306543"}},"subtitle":[],"editor":[{"given":"Wan-su","family":"Park","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,7,3]]},"references-count":77,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0306543","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,3]]}}}