{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:35:46Z","timestamp":1789760146189,"version":"4.0.1"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["2012\/01500-4"],"award-info":[{"award-number":["2012\/01500-4"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["2012\/14323-3"],"award-info":[{"award-number":["2012\/14323-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The isoflavone (3S)-vestitol, obtained from red propolis, has exhibited anti-inflammatory, antimicrobial, and anti-caries activity; however, few manuscripts deal with its anti-inflammatory mechanisms in macrophages. The objective is to elucidate the anti-inflammatory mechanisms of (3S)-vestitol on those cells. Peritoneal macrophages of C57BL6 mice, stimulated with lipopolysaccharide, were treated with 0.37 to 0.59 \u00b5M of (3S)-vestitol for 48 h. Then, nitric oxide (NO) quantities, macrophages viability, the release of 20 cytokines and the transcription of several genes related to cytokine production and inflammatory response were evaluated. The Tukey\u2013Kramer variance analysis test statistically analyzed the data. (3S)-vestitol 0.55 \u00b5M (V55) lowered NO release by 60% without altering cell viability and diminished IL-1\u03b2, IL-1\u03b1, G-CSF, IL-10 and GM-CSF levels. V55 reduced expression of Icam-1, Wnt5a and Mmp7 (associated to inflammation and tissue destruction in periodontitis) and Scd1, Scd2, Egf1 (correlated to atherosclerosis). V55 increased expression of Socs3 and Dab2 genes (inhibitors of cytokine signaling and NF-\u03baB pathway), Apoe (associated to atherosclerosis control), Igf1 (encoder a protein with analogous effects to insulin) and Fgf10 (fibroblasts growth factor). (3S)-vestitol anti-inflammatory mechanisms involve cytokines and NF-\u03baB pathway inhibition. Moreover, (3S)-vestitol may be a candidate for future in vivo investigations about the treatment\/prevention of persistent inflammatory diseases such as atherosclerosis and periodontitis.<\/jats:p>","DOI":"10.3390\/ph15050553","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T07:08:58Z","timestamp":1651475338000},"page":"553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Anti-Inflammatory Effects of (3S)-Vestitol on Peritoneal Macrophages"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3275-5910","authenticated-orcid":false,"given":"Bruno","family":"Bueno-Silva","sequence":"first","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-900, SP, Brazil"},{"name":"Dental Research Division, Guarulhos University, Guarulhos 07023-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela Rocha","family":"Bueno","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dione","family":"Kawamoto","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato C.","family":"Casarin","sequence":"additional","affiliation":[{"name":"Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Marcos Spessoto","family":"Pingueiro","sequence":"additional","affiliation":[{"name":"Dental Research Division, Guarulhos University, Guarulhos 07023-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6637-7973","authenticated-orcid":false,"given":"Severino Matias","family":"Alencar","sequence":"additional","affiliation":[{"name":"College of Agriculture \u201cLuiz de Queiroz\u201d (ESALQ\/USP), University of S\u00e3o Paulo, Piracicaba 13418-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Luiz","family":"Rosalen","sequence":"additional","affiliation":[{"name":"Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5910-8433","authenticated-orcid":false,"given":"Marcia Pinto Alves","family":"Mayer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.cell.2016.05.051","article-title":"Autophagy, Inflammation, and Immunity: A Troika Governing Cancer and Its Treatment","volume":"166","author":"Zhong","year":"2016","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Leyva-Lopez, N., Gutierrez-Grijalva, E.P., Ambriz-Perez, D.L., and Heredia, J.B. (2016). Flavonoids as Cytokine Modulators: A Possible Therapy for Inflammation-Related Diseases. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060921"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ferlazzo, N., Cirmi, S., Calapai, G., Ventura-Spagnolo, E., Gangemi, S., and Navarra, M. (2016). Anti-Inflammatory Activity of Citrus bergamia Derivatives: Where Do We Stand?. Molecules, 21.","DOI":"10.3390\/molecules21101273"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33720","DOI":"10.1038\/srep33720","article-title":"Tanshinones and diethyl blechnics with anti-inflammatory and anti-cancer activities from Salvia miltiorrhiza Bunge (Danshen)","volume":"6","author":"Gao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.3892\/or.2016.5108","article-title":"Baicalein inhibits TNF-alpha-induced NF-kappaB activation and expression of NF-kappaB-regulated target gene products","volume":"36","author":"Li","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/978-3-319-41334-1_12","article-title":"Celastrol and Its Role in Controlling Chronic Diseases","volume":"928","author":"Venkatesha","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100672","DOI":"10.1016\/j.jbior.2019.100672","article-title":"Abilities of beta-Estradiol to interact with chemotherapeutic drugs, signal transduction inhibitors and nutraceuticals and alter the proliferation of pancreatic cancer cells","volume":"75","author":"Akula","year":"2020","journal-title":"Adv. Biol. Regul."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.archoralbio.2016.03.016","article-title":"Extract of acai-berry inhibits osteoclast differentiation and activity","volume":"68","author":"Brito","year":"2016","journal-title":"Arch. Oral Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.3389\/fmicb.2017.02280","article-title":"Probiotic Bacteria Alter Pattern-Recognition Receptor Expression and Cytokine Profile in a Human Macrophage Model Challenged with Candida albicans and Lipopolysaccharide","volume":"8","author":"Matsubara","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_10","first-page":"1583","article-title":"Main pathways of action of Brazilian red propolis on the modulation of neutrophils migration in the inflammatory process","volume":"23","author":"Franchin","year":"2016","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.jep.2017.06.015","article-title":"Brazilian red propolis effects on peritoneal macrophage activity: Nitric oxide, cell viability, pro-inflammatory cytokines and gene expression","volume":"207","author":"Kawamoto","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.jff.2017.07.029","article-title":"Anti-inflammatory mechanisms of neovestitol from Brazilian red propolis in LPS-activated macrophages","volume":"36","author":"Rosalen","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrd4510","article-title":"The re-emergence of natural products for drug discovery in the genomics era","volume":"14","author":"Harvey","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/ecam\/nem059","article-title":"Chemical composition and botanical origin of red propolis, a new type of brazilian propolis","volume":"5","author":"Silva","year":"2008","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1021\/jf011432b","article-title":"Botanical origin and chemical composition of Brazilian propolis","volume":"50","author":"Park","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tiveron, A.P., Rosalen, P.L., Franchin, M., Lacerda, R.C., Bueno-Silva, B., Benso, B., Denny, C., Ikegaki, M., and Alencar, S.M. (2016). Chemical Characterization and Antioxidant, Antimicrobial, and Anti-Inflammatory Activities of South Brazilian Organic Propolis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165588"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4546","DOI":"10.1021\/jf305468f","article-title":"Anti-inflammatory and antimicrobial evaluation of neovestitol and vestitol isolated from Brazilian red propolis","volume":"61","author":"Alencar","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1080\/08927014.2013.834050","article-title":"Effect of neovestitol-vestitol containing Brazilian red propolis on accumulation of biofilm in vitro and development of dental caries in vivo","volume":"29","author":"Koo","year":"2013","journal-title":"Biofouling"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106329","DOI":"10.1016\/j.intimp.2020.106329","article-title":"Vestitol drives LPS-activated macrophages into M2 phenotype through modulation of NF-kappaB pathway","volume":"82","author":"Rosalen","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9927","DOI":"10.1021\/jf801870f","article-title":"GC-MS determination of isoflavonoids in seven red Cuban propolis samples","volume":"56","author":"Piccinelli","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1021\/acs.jnatprod.5b00938","article-title":"Vestitol Isolated from Brazilian Red Propolis Inhibits Neutrophils Migration in the Inflammatory Process: Elucidation of the Mechanism of Action","volume":"79","author":"Franchin","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"87","DOI":"10.2307\/2807701","article-title":"A synopsis of the genus Dalbergia (Fabaceae: Dalbergieae) in Brazil","volume":"49","year":"1997","journal-title":"Brittonia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nature17039","article-title":"Reparative inflammation takes charge of tissue regeneration","volume":"529","author":"Karin","year":"2016","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S1359-6101(97)00023-3","article-title":"Interleukin-1","volume":"8","author":"Dinarello","year":"1997","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bueno-Silva, B., Kawamoto, D., Ando-Suguimoto, E.S., Alencar, S.M., Rosalen, P.L., and Mayer, M.P. (2015). Brazilian Red Propolis Attenuates Inflammatory Signaling Cascade in LPS-Activated Macrophages. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144954"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Xie, W., Li, M., Xu, N., Lv, Q., Huang, N., He, J., and Zhang, Y. (2013). MiR-181a regulates inflammation responses in monocytes and macrophages. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058639"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/nri2356","article-title":"Colony-stimulating factors in inflammation and autoimmunity","volume":"8","author":"Hamilton","year":"2008","journal-title":"Nat. Reviews. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1056\/NEJMra052706","article-title":"Lineage-specific hematopoietic growth factors","volume":"354","author":"Kaushansky","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1172\/JCI79590","article-title":"Disabled homolog 2 controls macrophage phenotypic polarization and adipose tissue inflammation","volume":"126","author":"Adamson","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_31","unstructured":"(2022, April 27). Geneglobe quiagen. Available online: https:\/\/geneglobe.qiagen.com\/br\/explore\/pathway-details\/nf-kb-signaling."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1042\/BJ20140143","article-title":"Suppressor of cytokine signalling (SOCS) proteins as guardians of inflammatory responses critical for regulating insulin sensitivity","volume":"461","author":"Galic","year":"2014","journal-title":"Biochem. J."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nanbara, H., Wara-aswapati, N., Nagasawa, T., Yoshida, Y., Yashiro, R., Bando, Y., Kobayashi, H., Khongcharoensuk, J., Hormdee, D., and Pitiphat, W. (2012). Modulation of Wnt5a expression by periodontopathic bacteria. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034434"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1177\/0022034516687248","article-title":"Differential Expression and Roles of Secreted Frizzled-Related Protein 5 and the Wingless Homolog Wnt5a in Periodontitis","volume":"96","author":"Maekawa","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1002\/jcp.26086","article-title":"Wnt5a suppresses osteoblastic differentiation of human periodontal ligament stem cell-like cells via Ror2\/JNK signaling","volume":"233","author":"Hasegawa","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/j.joen.2013.06.015","article-title":"MMP-7 and TIMP-1, new targets in predicting poor wound healing in apical periodontitis","volume":"39","author":"Letra","year":"2013","journal-title":"J. Endod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/jcpe.12670","article-title":"Mucin 4 and matrix metalloproteinase 7 as novel salivary biomarkers for periodontitis","volume":"44","author":"Lundmark","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1182\/blood.V98.5.1429","article-title":"Lipopolysaccharide activation of the MEK-ERK1\/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor alpha expression by inducing Elk-1 phosphorylation and Egr-1 expression","volume":"98","author":"Guha","year":"2001","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Cao, C., Zhu, Y., Chen, W., Li, L., Qi, Y., Wang, X., Zhao, Y., Wan, X., and Chen, X. (2013). IKKepsilon knockout prevents high fat diet induced arterial atherosclerosis and NF-kappaB signaling in mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064930"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1161\/01.RES.0000112405.61577.95","article-title":"Early growth response-1 promotes atherogenesis: Mice deficient in early growth response-1 and apolipoprotein E display decreased atherosclerosis and vascular inflammation","volume":"94","author":"Harja","year":"2004","journal-title":"Circ. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Braesch-Andersen, S., Paulie, S., Smedman, C., Mia, S., and Kumagai-Braesch, M. (2013). ApoE production in human monocytes and its regulation by inflammatory cytokines. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079908"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1042\/BJ20100016","article-title":"Apolipoprotein E inhibits toll-like receptor (TLR)-3-and TLR-4-mediated macrophage activation through distinct mechanisms","volume":"428","author":"Zhu","year":"2010","journal-title":"Biochem. J."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"de Figueiredo, K.A., da Silva, H.D.P., Miranda, S.L.F., Goncalves, F., de Sousa, A.P., de Figueiredo, L.C., Feres, M., and Bueno-Silva, B. (2020). Brazilian Red Propolis Is as Effective as Amoxicillin in Controlling Red-Complex of Multispecies Subgingival Mature Biofilm In Vitro. Antibiotics, 9.","DOI":"10.3390\/antibiotics9080432"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1080\/08927014.2019.1598976","article-title":"Brazilian red propolis reduces orange-complex periodontopathogens growing in multispecies biofilms","volume":"35","author":"Miranda","year":"2019","journal-title":"Biofouling"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.seppur.2010.12.007","article-title":"Isolation and analysis of bioactive isoflavonoids and chalcone from a new type of Brazilian propolis","volume":"77","author":"Oldoni","year":"2011","journal-title":"Sep. Purif. Technol."},{"key":"ref_46","unstructured":"(2022, April 27). PubChem, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/177149#section=2D-Structure."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3389\/fcimb.2016.00033","article-title":"Alteration of Homeostasis in Pre-osteoclasts Induced by Aggregatibacter actinomycetemcomitans CDT","volume":"6","author":"Kawamoto","year":"2016","journal-title":"Front. Cell. Infect. Microbiol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/5\/553\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:04:26Z","timestamp":1760137466000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/5\/553"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,29]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ph15050553"],"URL":"https:\/\/doi.org\/10.3390\/ph15050553","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,29]]}}}