title: Elucidating the Role of Protandim and 6-Gingerol in Protection Against Osteoarthritis.
abstract: Protandim 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.
authors.affiliation: Orthopedic Research Laboratory, Hôpital du Sacré-Coeur de Montréal and Department of Surgery, Université de Montréal, 5400 Gouin Blvd. West, Montreal, Quebec, Canada H4J 1C5.
authors.forename: Jamilah
authors.initials: J
authors.lastname: Abusarah
authors.affiliation: Orthopedic Research Laboratory, Hôpital du Sacré-Coeur de Montréal and Department of Surgery, Université de Montréal, 5400 Gouin Blvd. West, Montreal, Quebec, Canada H4J 1C5.
authors.forename: Houda
authors.initials: H
authors.lastname: Benabdoune
authors.affiliation: Orthopedic Research Laboratory, Hôpital du Sacré-Coeur de Montréal and Department of Surgery, Université de Montréal, 5400 Gouin Blvd. West, Montreal, Quebec, Canada H4J 1C5.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Osteoarthritis Research Unit and Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM)-Hôpital Notre-Dame, Montreal, Quebec, Canada H2L 4M1.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lussier
authors.affiliation: Osteoarthritis Research Unit and Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM)-Hôpital Notre-Dame, Montreal, Quebec, Canada H2L 4M1.
authors.forename: Johanne
authors.initials: J
authors.lastname: Martel-Pelletier
authors.affiliation: Orthopedic Research Laboratory, Hôpital du Sacré-Coeur de Montréal and Department of Surgery, Université de Montréal, 5400 Gouin Blvd. West, Montreal, Quebec, Canada H4J 1C5.
authors.forename: Michel
authors.initials: M
authors.lastname: Malo
authors.affiliation: Orthopedic Research Laboratory, Hôpital du Sacré-Coeur de Montréal and Department of Surgery, Université de Montréal, 5400 Gouin Blvd. West, Montreal, Quebec, Canada H4J 1C5.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Fernandes
authors.affiliation: Universidade Estadual Paulista "Júlio de Mesquita Filho", (UNESP), Departamento de Física, Laboratório de Biologia Molecular, Centro Multiusuário de Inovação Biomolecular (CMIB), 15054-000, São José Do Rio Preto, SP, Brazil.
authors.forename: Fátima Pereira
authors.initials: FP
authors.lastname: de Souza
authors.affiliation: Osteoarthritis Research Unit and Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM)-Hôpital Notre-Dame, Montreal, Quebec, Canada H2L 4M1.
authors.forename: Hassan
authors.initials: H
authors.lastname: Fahmi
authors.affiliation: Orthopedic Research Laboratory, Hôpital du Sacré-Coeur de Montréal and Department of Surgery, Université de Montréal, 5400 Gouin Blvd. West, Montreal, Quebec, Canada H4J 1C5.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benderdour
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002396:Catechols / Q000008:administration & dosage* / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000494:pharmacology; D005233:Fatty Alcohols / Q000008:administration & dosage* / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007270:Injections, Intra-Articular; D053583:Interleukin-1beta / Q000009:adverse effects; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D002396:Catechols; D004365:Drugs, Chinese Herbal; D005233:Fatty Alcohols; D053583:Interleukin-1beta; D051267:NF-E2-Related Factor 2; C509374:Protandim; C007845:gingerol; D005982:Glutathione Transferase
keywords: CARTILAGE; GSTA4-4; HNE; Nrf2; OSTEOARTHRITIS; PROTANDIM