Chondroprotective Effect of Cynaroside in IL-1β-Induced Primary Rat Chondrocytes and Organ Explants via NF-κB and MAPK Signaling Inhibition.
Seul Ah LeeBo-Ram ParkSung-Min MoonJoon Ho HongDo-Kyung KimChun Sung KimPublished in: Oxidative medicine and cellular longevity (2020)
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. Interleukin-1β is the key player in the pathogenesis of OA, which induces the expression of various catabolic factors that contribute to cartilage degradation. Cynaroside (luteolin-7-O-glucoside or luteoloside) is a flavonoid that has various pharmacological properties, such as antitumor, anti-inflammatory, and antioxidant activities. In this study, we investigated the chondroprotective effects of cynaroside on IL-1β-stimulated chondrocytes and organ explants. The production of nitrite, PGE2, collagen type II, and aggrecan was measured by a Griess reagent and ELISAs, and the production of ROS was measured by H2DCF-DA fluorescence. The protein levels of iNOS, Cox-2, MMP-1, MMP-3, MMP-13, ADAMTS-4, MAPKs, and the NF-κB p65 subunit were measured by western blot. Proteoglycan analysis was performed by Alcian Blue staining (in vitro) and Safranin O staining (ex vivo). Cynaroside inhibited IL-1β-induced expression of catabolic factors (nitrite, iNOS, ROS, PGE2, Cox-2, MMP-1, MMP-3, MMP-13, and ADAMTS-4) and degradation of anabolic factors (collagen type II and aggrecan). Furthermore, cynaroside suppressed IL-1β-induced phosphorylation of MAPKs and translocation of the NF-κB p65 subunit into the nucleus. Collectively, these results suggest that cynaroside may be a potential candidate for the development of new therapeutic drugs for the alleviation of OA progression.
Keyphrases
- oxidative stress
- diabetic rats
- signaling pathway
- cell migration
- high glucose
- anti inflammatory
- poor prognosis
- pi k akt
- knee osteoarthritis
- dna damage
- lps induced
- nitric oxide
- drug induced
- nuclear factor
- extracellular matrix
- cell death
- binding protein
- endothelial cells
- rheumatoid arthritis
- high resolution
- small molecule
- toll like receptor
- south africa
- risk assessment
- protein protein