{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:38:29Z","timestamp":1784770709843,"version":"3.55.0"},"reference-count":41,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Endometriosis is an estrogen-linked gynecological disease defined by the presence of endometrial tissue on extrauterine sites where it forms invasive lesions. Alterations in estrogen-mediated cellular signaling seems to have an essential role in the pathogenesis of endometriosis. Higher estrogen receptor (ER)-\u03b2 levels and enhanced ER-\u03b2 activity were detected in endometriotic tissues. It is well known that ER-\u03b2 interacts with components of the cytoplasmic inflammasome-3 (NALP-3), the NALP-3 activation increases interleukin (IL)-1\u03b2 and IL-18, enhancing cellular adhesion and proliferation. Otherwise, the inhibition of ER-\u03b2 activity suppresses the ectopic lesions growth. The present study aims to investigate the potential effect of \u03b1-lipoic acid (ALA) on NALP-3 and ER-\u03b2 expression using a western blot analysis, NALP-3-induced cytokines production by ELISA, migration and invasion of immortalized epithelial (12Z) and stromal endometriotic cells (22B) using a 3D culture invasion assay, and matrix-metalloprotease (MMPs) activity using gelatin zymography. ALA significantly reduces ER-\u03b2, NALP-3 protein expression\/activity and the secretion of IL-1\u03b2 and IL-18 in both 12Z and 22B cells. ALA treatment reduces cellular adhesion and invasion via a lower expression of adhesion molecules and MMPs activities. These results provide convincing evidence that ALA might inhibit endometriosis progression.<\/jats:p>","DOI":"10.3390\/molecules26020288","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T21:21:45Z","timestamp":1610313705000},"page":"288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Alpha-Lipoic Acid Plays a Role in Endometriosis: New Evidence on Inflammasome-Mediated Interleukin Production, Cellular Adhesion and Invasion"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4776-1889","authenticated-orcid":false,"given":"Fiorella","family":"Di Nicuolo","sequence":"first","affiliation":[{"name":"Istituto Scientifico Internazionale PaoloVI, ISI, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Castellani","sequence":"additional","affiliation":[{"name":"Istituto di Clinica Ostetrica e Ginecologica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"De Cicco Nardone","sequence":"additional","affiliation":[{"name":"U.O.C. di Ostetricia e Patologia Ostetrica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Barbaro","sequence":"additional","affiliation":[{"name":"Istituto di Clinica Ostetrica e Ginecologica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Paciullo","sequence":"additional","affiliation":[{"name":"Istituto di Clinica Ostetrica e Ginecologica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Pontecorvi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Scambia","sequence":"additional","affiliation":[{"name":"U.O.C. Ginecologia Oncologica, Dipartimento per la Salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1273-3335","authenticated-orcid":false,"given":"Nicoletta","family":"Di Simone","sequence":"additional","affiliation":[{"name":"U.O.C. di Ostetricia e Patologia Ostetrica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1177\/1933719115584446","article-title":"Statins as Targeted \u201cMagical Pills\u201dfor the Conservative Treatment of Endometriosis: May Potential Adverse Effects On Female Fertility Represent the \u201cDark side of the Same Coin\u201d? A Systematic Review of Literature","volume":"23","author":"Vitagliano","year":"2016","journal-title":"Reprod. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nrurol.2017.58","article-title":"Pathophysiology and management of urinary tract endometriosis","volume":"14","author":"Nezhat","year":"2017","journal-title":"Nat. Rev. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"734","DOI":"10.3109\/09513590903159664","article-title":"Endometriosis in Italy: From cost estimates to new medical treatment","volume":"25","author":"Luisi","year":"2009","journal-title":"Gynecol. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.fertnstert.2011.05.090","article-title":"World Endometriosis Research Foundation Global Study of Women\u2019s Health consortium. Impact of endometriosis on quality of life and work productivity: A multicentre study across ten countries","volume":"96","author":"Nnoaham","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/1477-7827-12-50","article-title":"Molecular aspects of development and regulation of endometriosis","volume":"13","author":"Aznaurova","year":"2014","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.fertnstert.2012.06.029","article-title":"Pathogenesis and pathophysiology of endometriosis","volume":"98","author":"Burney","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"179515","DOI":"10.1155\/2014\/179515","article-title":"Theories on the pathogenesis of endometriosis","volume":"2014","author":"Sourial","year":"2014","journal-title":"Int. J. Reprod. Med."},{"key":"ref_8","first-page":"RA92","article-title":"Is abnormal eutopic endometrium the cause of endometriosis? The role of eutopic endometrium in pathogenesis of endoetriosis","volume":"17","author":"Liu","year":"2011","journal-title":"Med. Sci. Monit."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/j.1447-0756.2011.01734.x","article-title":"Effects of 17\u03b2\u2013estradiol on the release of monocyte chemotactic protein-1 and MAPK activity in monocytes stimulated with peritioneal fluid from endometriosis patients","volume":"38","author":"Lee","year":"2012","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1177\/1933719111430998","article-title":"Statins inhibit monocyte chemotactic protein 1 expression in endometriosis","volume":"19","author":"Cakmak","year":"2012","journal-title":"Reprod. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.fertnstert.2004.04.038","article-title":"Lipopolysaccharide-promoted proliferation of endometriotic stromal cells via induction of tumor necrosis factor alpha and interleukin-8 expression","volume":"82","author":"Iba","year":"2004","journal-title":"Fertil. Steril."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1210\/jc.2008-2218","article-title":"Increased production of 17 beta-estradiol in endometriosis lesions is the result of impaired metabolism","volume":"94","author":"Delvoux","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3960","DOI":"10.1210\/en.2012-1294","article-title":"Role of estrogen receptor signalling required for endometriosis-like lesion established in a mouse model","volume":"153","author":"Burns","year":"2012","journal-title":"Endocrinology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2015.10.034","article-title":"Estrogen receptor \u03b2 modulates apoptosis complexes and the inflammasome to drive the pathogenesis of endometriosis","volume":"163","author":"Han","year":"2015","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dutartre, P. (2016). Inflammasomes and Natural Ingredients towards New Anti-Inflammatory Agents. Molecules, 21.","DOI":"10.3390\/molecules21111492"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"455","DOI":"10.2174\/0929866525666180412160045","article-title":"An Emerging Role of Endometrial Inflammasome in Reproduction: New Therapeutic Approaches","volume":"25","author":"Specchia","year":"2018","journal-title":"Protein Pept. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1007\/s00018-016-2205-2","article-title":"The intersection of cell death and inflammasome activation","volume":"73","author":"Vince","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.fertnstert.2015.09.027","article-title":"Inflammosome in the human endometrium: Further step in the evaluation of the \u201cmaternal side\u201d","volume":"105","author":"Tersigni","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e13153","DOI":"10.1111\/aji.13153","article-title":"Effect of alpha-lipoic acid and myoinositol on endometrial inflammasome from recurrent pregnancy loss women","volume":"82","author":"Castellani","year":"2019","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_20","first-page":"2250","article-title":"Searching of Protein Targets for Alpha Lipoic Acid","volume":"22","year":"2011","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Salehi, B., Berkay Y\u0131lmaz, Y., Antika, G., Tumer, T.B., Mahomoodally, M.F., Lobine, D., Akram, M., Riaz, M., Capanoglu, E., and Shaporov, F. (2019). Insights on the Use of \u03b1-Lipoic Acid for Therapeutic Purposes. Biomolecules, 9.","DOI":"10.3390\/biom9080356"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1097\/FJC.0b013e3181be7554","article-title":"Antioxidant properties of an endogenous thiol: Alpha-lipoic acid, useful in the prevention of cardiovascular diseases","volume":"54","author":"Ghibu","year":"2009","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1007\/s00011-017-1079-6","article-title":"Biochemical and clinical relevance of alpha lipoic acid: Antioxidant and anti-inflammatory activity, molecular pathways and therapeutic potential","volume":"66","author":"Tibullo","year":"2017","journal-title":"Inflamm. Res."},{"key":"ref_24","first-page":"1016","article-title":"The potent antioxidant alpha lipoic acid","volume":"2","author":"Hussein","year":"2017","journal-title":"J. Plant Chem. Ecophysiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1042\/CS20120560","article-title":"\u03b1-Lipoic acid enhances endogenous peroxisome-proliferator-activated receptor-\u03b3 to ameliorate experimental autoimmune encephalomyelitis in mice","volume":"125","author":"Wang","year":"2013","journal-title":"Clin. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.bbagen.2009.07.026","article-title":"Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential","volume":"1790","author":"Shay","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s11033-012-2071-4","article-title":"Lipoic acid attenuates the expression of adhesion molecules by increasing endothelial mitric-oxide synthase activity","volume":"40","author":"Jin","year":"2013","journal-title":"Mol. Biol. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1093\/humrep\/deh711","article-title":"A selective estrogen receptor-beta agonist causes lesion regression in an experimentally induced model of endometriosis","volume":"20","author":"Harris","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1093\/humupd\/dmu059","article-title":"A clear and present danger: Inflammasomes DAMPing down disorders of pregnancy","volume":"21","author":"Khan","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1177\/1933719112459240","article-title":"Bacterial LPS differently modulates inflammasome gene expression and IL-1\u03b2 secretion in trophoblast cells, decidual stromal cells, and decidual endothelial cells","volume":"20","author":"Pontillo","year":"2013","journal-title":"Reprod. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1002\/eji.201141550","article-title":"A clinical perspective of IL-1\u03b2 as the gatekeeper of inflammation","volume":"41","author":"Dinarello","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nri2691","article-title":"The IL-1 family: Regulators of immunity","volume":"10","author":"Sims","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.semnephrol.2006.09.013","article-title":"Interleukin-18 and the pathogenesis of inflammatory diseases","volume":"27","author":"Dinarello","year":"2007","journal-title":"Semin. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1586\/1744666X.1.4.619","article-title":"Interleukin-18 treatment options for inflammatory diseases","volume":"1","author":"Dinarello","year":"2005","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1007\/s10875-010-9440-3","article-title":"Molecular mechanism of NLRP3 inflammasome activation","volume":"30","author":"Jin","year":"2010","journal-title":"J. Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Netea, M.G., Simon, A., Van De Veerdonf, F., Kullberg, B.J., Van Der Meer, J.W., and Joosten, L.A. (2010). Il-1beta processing in host defence: Beyond the inflammasomes. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000661"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Park, C., Jeong, J.W., Lee, D.S., Yim, M.J., Lee, J.M., Han, M.H., Kim, S., Kim, H.S., Kim, G.K., and Park, E.K. (2018). Sargassum serratifolium extract attenuates interleukin-1\u03b2-induced oxidative stress and inflammatory response in chondrocytes by suppressing the activation of NF-kB, p38 MAPK, and PI3K\/Akt. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082308"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sulistyowati, E., Lee, M.Y., Wu, L.C., Hsu, J.H., Dai, Z.K., Wu, B.N., Lin, M.C., and Yen, J.L. (2018). Exogenus heat shock cognate protein 70 suppresses LPS-Induced inflammation by down-regulating NF-kB through MAPK and MMP-2\/-9 pathways in macrophages. Molecules, 23.","DOI":"10.3390\/molecules23092124"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.abb.2018.08.003","article-title":"Alpha-lipoic acid, but not di-hydrolipoic acid, activates Nrf2 response in primary human umbilical-vein endothelial cells and protects against TNF-\u03b1 induced endothelium dysfunction","volume":"655","author":"Fratantonio","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00011-010-0256-7","article-title":"Evidence that \u03b1-lipoic acid inhibits NF-\u03baB activation independent of its antioxidant function","volume":"60","author":"Ying","year":"2011","journal-title":"Inflamm. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1016\/j.fertnstert.2010.01.038","article-title":"Selective blockade of prostaglandin E2 receptors EP2 and EP4 signalling inhibits proliferation of human endometriotic epithelial cells and stromal cells through distinct cell cycle arrest","volume":"93","author":"Lee","year":"2010","journal-title":"Fertil. Steril."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/2\/288\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:08:41Z","timestamp":1760159321000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/2\/288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,8]]},"references-count":41,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["molecules26020288"],"URL":"https:\/\/doi.org\/10.3390\/molecules26020288","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,8]]}}}