1. Downregulating Akt/NF-κB signaling and its antioxidant activity with Loureirin A for alleviating the progression of osteoarthritis: In vitro and vivo studies.
- Author
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Hu SL, Wang K, Shi YF, Shao ZX, Zhang CX, Sheng KW, Ge ZD, Chen JX, and Wang XY
- Subjects
- Animals, Anti-Inflammatory Agents pharmacology, Antioxidants pharmacology, Cell Survival drug effects, Cells, Cultured, Chalcones pharmacology, Chondrocytes drug effects, Chondrocytes metabolism, Chondrocytes pathology, Down-Regulation drug effects, Extracellular Matrix drug effects, Female, Male, Malondialdehyde metabolism, Mice, Inbred C57BL, NF-kappa B metabolism, Osteoarthritis metabolism, Proto-Oncogene Proteins c-akt metabolism, Reactive Oxygen Species metabolism, Signal Transduction drug effects, Superoxide Dismutase metabolism, Anti-Inflammatory Agents therapeutic use, Antioxidants therapeutic use, Chalcones therapeutic use, Osteoarthritis drug therapy
- Abstract
Osteoarthritis(OA) is one of the most common diseases in orthopedics. It is characterized by degeneration of articular cartilage and chronic inflammation. In this study, we aim to elucidate the mechanism of Loureirin A's therapeutic effect in OA progression. In vitro, Loureirin A pretreatment can significantly inhibit production of NO, PGE2, COX-2, TNF-α, iNOS andIL-6 induced by IL-1β in mouse articular chondrocytes. Moreover, Loureirin A suppressed the expression of matrix metalloproteinase-9(MMP-9), which leads to degradation of the extracellular matrix. The degradation of aggrecan and type II collagen protein in the extracellular matrix (ECM) stimulated by IL-1β was reversed. For signal pathway research, Loureirin A dramatically inhibited the phosphorylation of AKT and subsequent NF-κB entering into the nucleus caused by IL-1β in chondrocytes. Besides, a number of related indicators suggested that Loureirin A has a strong antioxidant activity in the treatment of osteoarthritis via increasing content of SOD2 and suppressing MDA and ROS. In addition, in vivo study demonstrated that Loureirin A could ameliorated the progression of OA in mice DMM model In conclusion, all results showed that Loureirin A may be a potential therapeutic candidate for the OA., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
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