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J Cell Biochem. 2017 May;118(5):1003-1013. doi: 10.1002/jcb.25659. Epub 2017 Jan 5.

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

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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.
Osteoarthritis Research Unit and Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM)-Hôpital Notre-Dame, Montreal, Quebec, Canada H2L 4M1.
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.


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.



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