Elucidating the Role of Protandim and 6‐Gingerol in Protection Against Osteoarthritis
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Bibliographic record
Abstract
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 2 , 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.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it