Elucidating the Role of Protandim and 6-Gingerol in Protection Against Osteoarthritis

dc.contributor.authorAbusarah, Jamilah
dc.contributor.authorBenabdoune, Houda
dc.contributor.authorShi, Qin
dc.contributor.authorLussier, Bertrand
dc.contributor.authorMartel-Pelletier, Johanne
dc.contributor.authorMalo, Michel
dc.contributor.authorFernandes, Julio C.
dc.contributor.authorde Souza, Fátima Pereira [UNESP]
dc.contributor.authorFahmi, Hassan
dc.contributor.authorBenderdour, Mohamed
dc.contributor.institutionUniversité de Montréal
dc.contributor.institutionCentre hospitalier de l'Université de Montréal (CRCHUM)—Hôpital Notre-Dame
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2018-12-11T17:08:47Z
dc.date.available2018-12-11T17:08:47Z
dc.date.issued2017-05-01
dc.description.abstractProtandim and 6-gingerol, two potent nutraceuticals, have been shown to decrease free radicals production through enhancing endogenous antioxidant enzymes. In this study, we evaluated the effects of these products on the expression of different factors involved in osteoarthritis (OA) process. Human OA chondrocytes were treated with 1 ng/ml IL-1β in the presence or absence of protandim (0–10 μg/ml) or 6-gingerol (0–10 μM). OA was induced surgically in mice by destabilization of the medial meniscus (DMM). The animals were treated weekly with an intraarticular injection of 10 μl of vehicle or protandim (10 μg/ml) for 8 weeks. Sham-operated mice served as controls. In vitro, we demonstrated that protandim and 6-gingerol preserve cell viability and mitochondrial metabolism and prevented 4-hydroxynonenal (HNE)-induced cell mortality. They activated Nrf2 transcription factor, abolished IL-1β-induced NO, PGE2, MMP-13, and HNE production as well as IL-β-induced GSTA4-4 down-regulation. Nrf2 overexpression reduced IL-1β-induced HNE and MMP-13 as well as IL-1β-induced GSTA4-4 down-regulation. Nrf2 knockdown following siRNA transfection abolished protandim protection against oxidative stress and catabolism. The activation of MAPK and NF-κB by IL-1β was not affected by 6-gingerol. In vivo, we observed that Nrf2 and GSTA4-4 expression was significantly lower in OA cartilage from humans and mice compared to normal controls. Interestingly, protandim administration reduced OA score in DMM mice. Altogether, our data indicate that protandim and 6-gingerol are essential in preserving cartilage and abolishing a number of factors known to be involved in OA pathogenesis. J. Cell. Biochem. 118: 1003–1013, 2017. © 2016 Wiley Periodicals, Inc.en
dc.description.affiliationOrthopedic Research Laboratory Hôpital du Sacré-Coeur de Montréal and Department of Surgery Université de Montréal, 5400 Gouin Blvd. West
dc.description.affiliationOsteoarthritis Research Unit and Research Centre Centre hospitalier de l'Université de Montréal (CRCHUM)—Hôpital Notre-Dame
dc.description.affiliationUniversidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP) Departamento de Física Laboratório de Biologia Molecular, Centro Multiusuário de Inovação Biomolecular (CMIB), 15054–000
dc.description.affiliationUnespUniversidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP) Departamento de Física Laboratório de Biologia Molecular, Centro Multiusuário de Inovação Biomolecular (CMIB), 15054–000
dc.description.sponsorshipCanadian Institutes of Health Research
dc.description.sponsorshipIdCanadian Institutes of Health Research: #IMH 131570
dc.format.extent1003-1013
dc.identifierhttp://dx.doi.org/10.1002/jcb.25659
dc.identifier.citationJournal of Cellular Biochemistry, v. 118, n. 5, p. 1003-1013, 2017.
dc.identifier.doi10.1002/jcb.25659
dc.identifier.issn1097-4644
dc.identifier.issn0730-2312
dc.identifier.lattes3313511334783986
dc.identifier.orcid0000-0002-4731-4977
dc.identifier.scopus2-s2.0-85008199859
dc.identifier.urihttp://hdl.handle.net/11449/174025
dc.language.isoeng
dc.relation.ispartofJournal of Cellular Biochemistry
dc.relation.ispartofsjr1,209
dc.relation.ispartofsjr1,209
dc.rights.accessRightsAcesso restrito
dc.sourceScopus
dc.subjectCARTILAGE
dc.subjectGSTA4-4
dc.subjectHNE
dc.subjectNrf2
dc.subjectOSTEOARTHRITIS
dc.subjectPROTANDIM
dc.titleElucidating the Role of Protandim and 6-Gingerol in Protection Against Osteoarthritisen
dc.typeArtigo
unesp.author.lattes3313511334783986[8]
unesp.author.orcid0000-0002-4731-4977[8]

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