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, PGE , 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.

Wogonin, a plant derived small molecule, exerts potent anti-inflammatory and chondroprotective effects through the activation of ROS/ERK/Nrf2 signaling pathways in human Osteoarthritis chondrocytes

“…5I). These results are in agreement with a recent report demonstrating that Nrf2 over-expression reduced the production of MMP-13 in IL-1β stimulated OA chondrocytes [48]. Collectively, these results demonstrate that Wogonin is a potent inducer of anabolic genes in OA chondrocytes in vitro and has the potential to suppress matrix degradation in vivo .…”

“…A recent study using nutraceuticals showed that protandim and 6-gingerol mediated Nrf2 activation offers protection against IL-1β-induced NO and PGE 2 production in OA chondrocytes [48]. Wogonin treatment of OA chondrocytes under stimulation with IL-1β completely inhibited the expression and production of varieties of inflammatory mediators including COX-2, PGE 2 , iNOS, NO, IL-6 and MMP-13 in human OA chondrocytes (Fig.…”

6-Gingerol protects cardiocytes H9c2 against hypoxia-induced injury by suppressing BNIP3 expression

“…As a consequence, inhibition of cell death is regarded as an attractive approach to control cardiac disease. It has been reported that 6 G exerts cellular protective effects against radiation-induced cell damage [29], 4-hydroxynonenalinduced cells mortality [19], amyloid-b-induced pheochromocytoma cells injury [30], and chlorpyrifos-induced oxidative damage in the brain, ovary and uterus [18]. The cyto-protection of 6 G has also been elucidated in hypoxia-induced injury [20].…”

“…6-Gingerol (6 G) is a natural chemical compound isolated from ginger (Zingiber officinale). Specifically, 6 G has been indicated to possess potential efficacies against tumour [11][12][13][14][15][16], oxidative stress and inflammation [17][18][19]. Moreover, potent protection of 6 G against hypoxia/reoxygenation-induced injury has been recently elucidated.…”

Could Oxidative Stress Regulate the Expression of MicroRNA-146a and MicroRNA-34a in Human Osteoarthritic Chondrocyte Cultures?

“…The chondroprotective effects of some antioxidant substances, such as gingerol and wogonin, have been demonstrated in human OA chondrocytes, through the activation of NRF2 signaling pathway [ 57 , 58 ]. No previous data was available regarding the effect of taurine on this transcription factor, so we showed for the first time a significant increase in NRF2 mRNA levels in the H 2 O 2 -stimulated chondrocyte cultures after treatment with taurine at a concentration of 200 μM.…”