{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:47:36Z","timestamp":1790092056607,"version":"4.0.1"},"reference-count":37,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Funda\u00e7\u00e3o Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["310571\/2020-0"],"award-info":[{"award-number":["310571\/2020-0"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["310571\/2020-0"],"award-info":[{"award-number":["310571\/2020-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Capsaicin, a bioactive compound found in peppers, is recognized for its anti-inflammatory, antioxidant, and anti-lipidemic properties. This study aimed to evaluate the effects of capsaicin on atherosclerosis progression. Methods: Apolipoprotein E knockout mice and their C57BL\/6 controls were utilized to assess blood lipid profile, inflammatory status, and atherosclerotic lesions. We also examined the influence of capsaicin on cholesterol influx and efflux, and the role of TRPV1 and PPAR\u03b3 signaling pathways in bone marrow-derived macrophages. Results: Capsaicin treatment reduced weight gain, visceral adiposity, blood triglycerides, and total and non-HDL cholesterol. These improvements were associated with a reduction in atherosclerotic lesions in the aorta and carotid. Capsaicin also improved hepatic oxidative and inflammatory status. Systemic inflammation was also reduced, as indicated by reduced leukocyte rolling and adhesion on the mesenteric plexus. Capsaicin decreased foam cell formation by reducing cholesterol influx through scavenger receptor A and increasing cholesterol efflux via ATP-binding cassette transporter A1, an effect primarily linked to TRPV1 activation. Conclusions: These findings underscore the potential of capsaicin as a promising agent for atherosclerosis prevention, highlighting its comprehensive role in modulating lipid metabolism, foam cell formation, and inflammatory responses.<\/jats:p>","DOI":"10.3390\/nu16183167","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T08:12:27Z","timestamp":1726733547000},"page":"3167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Capsaicin Improves Systemic Inflammation, Atherosclerosis, and Macrophage-Derived Foam Cells by Stimulating PPAR Gamma and TRPV1 Receptors"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8409-7705","authenticated-orcid":false,"given":"Danielle Lima","family":"\u00c1vila","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8349-7099","authenticated-orcid":false,"given":"Weslley","family":"Fernandes-Braga","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6975-1289","authenticated-orcid":false,"given":"Janayne Luihan","family":"Silva","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5017-2500","authenticated-orcid":false,"given":"Elandia Aparecida","family":"Santos","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianne","family":"Campos","sequence":"additional","affiliation":[{"name":"Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola Caroline Lacerda","family":"Leoc\u00e1dio","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano Santos Aggum","family":"Capettini","sequence":"additional","affiliation":[{"name":"Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edenil Costa","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6601-9853","authenticated-orcid":false,"given":"Jacqueline Isaura","family":"Alvarez-Leite","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1124\/dmd.107.019240","article-title":"In vitro hepatic and skin metabolism of capsaicin","volume":"36","author":"Chanda","year":"2008","journal-title":"Drug Metab. Dispos."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102870","DOI":"10.1016\/j.ceca.2024.102870","article-title":"TRPV1: Receptor structure, activation, modulation and role in neuro-immune interactions and pain","volume":"119","author":"TMaximiano","year":"2024","journal-title":"Cell Calcium"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Silva, J.L., Santos, E.A., and Alvarez-Leite, J.I. (2023). Are We Ready to Recommend Capsaicin for Disorders Other Than Neuropathic Pain?. Nutrients, 15, (In English).","DOI":"10.20944\/preprints202309.1822.v1"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nawaka, N., Wanmasae, S., Makarasen, A., Dechtrirat, D., Techasakul, S., and Jeenduang, N. (2022). Allicin and Capsaicin Ameliorated Hypercholesterolemia by Upregulating LDLR and Downregulating PCSK9 Expression in HepG2 Cells. Int. J. Mol. Sci., 23, (In English).","DOI":"10.3390\/ijms232214299"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3892\/mmr.2023.13042","article-title":"Improvement of wound healing by capsaicin through suppression of the inflammatory response and amelioration of the repair process","volume":"28","author":"Huang","year":"2023","journal-title":"Mol. Med. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1097\/AJP.0b013e318227403d","article-title":"NGX-4010, a capsaicin 8% dermal patch, administered alone or in combination with systemic neuropathic pain medications, reduces pain in patients with postherpetic neuralgia","volume":"28","author":"Irving","year":"2012","journal-title":"Clin. J. Pain"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Thongin, S., Den-Udom, T., Uppakara, K., Sriwantana, T., Sibmooh, N., Laolob, T., Boonthip, C., Wichai, U., Muta, K., and Ketsawatsomkron, P. (2022). Beneficial effects of capsaicin and dihydrocapsaicin on endothelial inflammation, nitric oxide production and antioxidant activity. Biomed. Pharmacother., 154, (In English).","DOI":"10.1016\/j.biopha.2022.113521"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3892\/mmr.2024.13162","article-title":"Pharmacological activity of capsaicin: Mechanisms and controversies (Review)","volume":"29","author":"Zhang","year":"2024","journal-title":"Mol. Med. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kim, H.J. (2023). Capsaicin supplementation prevents western diet-induced hyperleptinemia by reducing endoplasmic reticulum stress in apolipoprotein E-deficient mice. Food Nutr. Res., 67, (In English).","DOI":"10.29219\/fnr.v67.9610"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1089\/jmf.2010.1367","article-title":"Dietary capsaicin attenuates metabolic dysregulation in genetically obese diabetic mice","volume":"14","author":"Kang","year":"2011","journal-title":"J. Med. Food"},{"key":"ref_11","first-page":"e1861","article-title":"A model of disturbed flow-induced atherosclerosis in mouse carotid artery by partial ligation and a simple method of RNA isolation from carotid endothelium","volume":"40","author":"Nam","year":"2010","journal-title":"J. Vis. Exp."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.numecd.2014.01.002","article-title":"Butyrate impairs atherogenesis by reducing plaque inflammation and vulnerability and decreasing NF\u03baB activation","volume":"24","author":"Aguilar","year":"2014","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.jnutbio.2011.01.007","article-title":"Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis","volume":"23","author":"Vieira","year":"2012","journal-title":"J. Nutr. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/1476-511X-10-204","article-title":"The combination of high-fat diet-induced obesity and chronic ulcerative colitis reciprocally exacerbates adipose tissue and colon inflammation","volume":"10","author":"Teixeira","year":"2011","journal-title":"Lipids Health Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0076-6879(86)28068-4","article-title":"Single vertical spin density gradient ultracentrifugation","volume":"128","author":"Chung","year":"1986","journal-title":"Methods Enzymol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0022-2275(20)40759-X","article-title":"Rapid fluorometric assay of LDL receptor activity by DiI-labeled LDL","volume":"34","author":"Stephan","year":"1993","journal-title":"J. Lipid Res."},{"key":"ref_18","first-page":"21","article-title":"The atheroprotective role of fucoidan involves the reduction of foam cell formation by altering cholesterol flux-associated factors in macrophages","volume":"650","author":"Aguilar","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/sj.bjp.0705533","article-title":"Signal transduction for inhibition of inducible nitric oxide synthase and cyclooxygenase-2 induction by capsaicin and related analogs in macrophages","volume":"140","author":"Chen","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"925171","DOI":"10.1155\/2013\/925171","article-title":"Activation of TRPV1 prevents OxLDL-induced lipid accumulation and TNF-\u03b1-induced inflammation in macrophages: Role of liver X receptor \u03b1","volume":"2013","author":"Zhao","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.taap.2012.06.014","article-title":"A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4","volume":"263","author":"Min","year":"2012","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/1475-2840-11-139","article-title":"Telmisartan ameliorates insulin sensitivity by activating the AMPK\/SIRT1 pathway in skeletal muscle of obese db\/db mice","volume":"11","author":"Shiota","year":"2012","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00424-012-1078-y","article-title":"TRPV1 activation prevents nonalcoholic fatty liver through UCP2 upregulation in mice","volume":"463","author":"Li","year":"2012","journal-title":"Pflug. Arch."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"E315","DOI":"10.1152\/ajpendo.00354.2014","article-title":"A combination of exercise and capsinoid supplementation additively suppresses diet-induced obesity by increasing energy expenditure in mice","volume":"308","author":"Ohyama","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hu, Y.-W., Ma, X., Huang, J.-L., Mao, X.-R., Yang, J.-Y., Zhao, J.-Y., Li, S.-F., Qiu, Y.-R., Yang, J., and Zheng, L. (2013). Dihydrocapsaicin Attenuates Plaque Formation through a PPAR\u03b3\/LXR\u03b1 Pathway in apoE(\u2212\/\u2212) Mice Fed a High-Fat\/High-Cholesterol Diet. PLoS ONE, 8, (In English).","DOI":"10.1371\/journal.pone.0066876"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zheng, Y., Shao, M., Zheng, Y., Sun, W., Qin, S., Sun, Z., Zhu, L., Guan, Y., Wang, Q., and Wang, Y. (2024). PPARs in atherosclerosis: The spatial and temporal features from mechanism to druggable targets. J. Adv. Res., 29, (In English).","DOI":"10.1016\/j.jare.2024.03.020"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Khan, A.A., Alsahli, M.A., and Rahmani, A.H. (2018). Myeloperoxidase as an Active Disease Biomarker: Recent Biochemical and Pathological Perspectives. Med. Sci., 6, (In English).","DOI":"10.20944\/preprints201802.0104.v1"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez, L., Rivera, K., Andia, M.E., and Rodriguez, G.M. (2022). The IL-1 Family and Its Role in Atherosclerosis. Int. J. Mol. Sci., 24, (In English).","DOI":"10.3390\/ijms24010017"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1093\/cvr\/cvr245","article-title":"Activation of TRPV1 reduces vascular lipid accumulation and attenuates atherosclerosis","volume":"92","author":"Ma","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1146\/annurev.cellbio.042308.113238","article-title":"Rolling cell adhesion","volume":"26","author":"McEver","year":"2010","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1097\/MPA.0b013e3181a5ef3a","article-title":"Capsaicin reduces tissue damage in experimental acute pancreatitis","volume":"38","author":"Schneider","year":"2009","journal-title":"Pancreas"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0898-6568(02)00086-4","article-title":"Capsaicin exhibits anti-inflammatory property by inhibiting IkB-a degradation in LPS-stimulated peritoneal macrophages","volume":"15","author":"Kim","year":"2003","journal-title":"Cell Signal"},{"key":"ref_33","first-page":"136","article-title":"CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterial intima","volume":"119","author":"Park","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.intimp.2015.06.007","article-title":"Capsaicin attenuates LPS-induced inflammatory cytokine production by upregulation of LXRalpha","volume":"28","author":"Tang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.prostaglandins.2006.06.006","article-title":"PPARgamma activation induces CD36 expression and stimulates foam cell like changes in rVSMCs","volume":"80","author":"Lim","year":"2006","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/83301","article-title":"Progress in cardiovascular biology: PPAR for the course","volume":"7","author":"Lazar","year":"2001","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3242","DOI":"10.4049\/jimmunol.179.5.3242","article-title":"Individual variation of scavenger receptor expression in human macrophages with oxidized low-density lipoprotein is associated with a differential inflammatory response","volume":"179","author":"Civeira","year":"2007","journal-title":"J. Immunol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/18\/3167\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:59:31Z","timestamp":1760111971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/18\/3167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,19]]},"references-count":37,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["nu16183167"],"URL":"https:\/\/doi.org\/10.3390\/nu16183167","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,19]]}}}