Effects of baicalein on IL-1β-induced inflammation and apoptosis in rat articular chondrocytes

Abstract

In osteoarthritis (OA), activated synoviocytes and articular chondrocytes produce pro-inflammatory cytokines, such as IL-1β, that promote chondrocyte apoptosis and activate the NF-κB signaling pathway to induce catabolic factors. In this study, we examined the anti-inflammatory and anti-apoptotic effect of baicalein on IL-1β signaling and NF-κB-regulated gene products in rat chondrocytes. Rat chondrocytes were pretreated with 10 ng/ml IL-1β for 24 h and then co-treated with 10 ng/ ml IL-1β and 50 μM baicalein for 0, 12, 24, 36 and 48h. The expression levels of poly(ADP-ribose) polymerase (PARP), Bcl-2, caspase-3, matrix metalloproteinase (MMP)-9, MMP-3, cyclooxygenase (COX)-2 and SOX-9 were detected by Western blot and quantitative reverse transcription-PCR (qPCR). The effects of baicalein on the translocation and phosphorylation of the NF-κB system were studied by Western blotting and immunofluorescence. Baicalein stimulated the expression of anti-apoptotic genes and reduced the pro-apoptotic and pro-inflammatory gene products in chondrocytes. Baicalein promoted SOX-9 expression in a time-dependent manner in chondrocytes. Baicalein inhibited the NF-κB activation that was induced by IL-1β in a time-dependent manner in chondrocytes. Our results suggest that the anti-inflammatory and anti-apoptotic effects of baicalein are mediated through the inhibition of the translocation of phosphorylated p65 to the nucleus.

Aminoguanidine inhibits IL‑1β‑induced protein expression of iNOS and COX‑2 by blocking the NF‑κB signaling pathway in rat articular chondrocytes

“…IL-1β is involved in the pathogenesis of OA and it may result in marked alterations to the cartilage, including matrix degradation, inflammation, chondrocyte phenotypic changes and chondrocyte apoptosis ( 26 , 37-39 ). Previous studies have reported that 10 ng/ml IL-1β induces an inflammatory response in chondrocytes ( 27 , 40 ); therefore, 10 ng/ml was used as the working concentration of IL-1β in the present study. IL-1β induces iNOS and COX-2 expression, promotes the synthesis of inflammatory mediators, including prostaglandin E2 and nitric oxide, and stimulates articular chondrocytes to produce high levels of NF-κB ( 26 ).…”

“…As previously described (27), cartilage debris was isolated with trypsin (Gibco; Thermo Fisher Scientific, Inc.) at 37˚C for 30 min, and subsequently rinsed with PBS containing penicillin and streptomycin solution. The tissue was digested with collagenase Type II (Gibco; Thermo Fisher Scientific, Inc.) in PBS at 37˚C for 4 h. Subsequently, the supernatant was collected and centrifuged at 500 x g, 27˚C for 7 min.…”

Therapeutic potential of hyaluronic acid/chitosan nanoparticles for the delivery of curcuminoid in knee osteoarthritis and an in�vitro evaluation in chondrocytes

“…Therefore, HA/CNP can be used to inhibit the NF-κB pathway by increasing IκB. Moreover, Li et al have proved that inhibiting phosphorylated P65 translocation to the nucleus can promote the effect of baicalein against chondrocyte inflammation and apoptosis ( 22 ). Therefore, inhibiting P65 translocation to the nucleus may be a target for OA therapy.…”

Emerging Natural-Product-Based Treatments for the Management of Osteoarthritis

“…Baicalein is a flavonoid (5,6,7-trihydroxyflavone) that is isolated from the roots of Scutellaria baicalensis and Scutellaria lateriflora and has medicinal properties, including neuroprotective, anti-oxidant, anti-fibrosis, and anti-cancer properties [ 40 , 41 ]. Recently, it has been demonstrated that baicalein has anti-catabolic and anti-apoptotic effects through inhibiting IL-1β induction in chondrocytes [ 42 , 43 ]. Another study showed that the intra-articular injection of medium and high doses of baicalein alleviated OA progression in a rabbit OA model, diminishing cartilage degradation, and showing a lower Mankin score [ 44 ].…”