Downregulating Akt/NF-κB signaling and its antioxidant activity with Loureirin A for alleviating the progression of osteoarthritis: In vitro and vivo studies

Int Immunopharmacol. 2020 Jan:78:105953. doi: 10.1016/j.intimp.2019.105953. Epub 2019 Nov 26.

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.

Keywords: Inflammation; Loureirin A; Osteoarthritis; Oxidative stress.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chalcones / pharmacology
  • Chalcones / therapeutic use*
  • 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 / drug therapy*
  • Osteoarthritis / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Superoxide Dismutase / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Chalcones
  • NF-kappa B
  • Reactive Oxygen Species
  • loureirin A
  • Malondialdehyde
  • Superoxide Dismutase
  • superoxide dismutase 2
  • Proto-Oncogene Proteins c-akt