Osteoarthritis (OA) is a common degenerative
joint disease featuring the degeneration, destruction, and ossification of cartilage.
Inflammation which may facilitate OA occurrence and development is considered as the main pathological factor.
Betulin, a
natural product extracted from birch bark, has been commonly used for
inflammation treatment; however, its role in OA remains unclear. This study is aimed to explore whether
betulin can suppress IL-1β-induced
inflammation in chondrocytes and alleviate OA in vitro and in vivo. In in vitro studies, the generation of pro-inflammatory factors, such as
interleukin-6 (IL-6),
tumor necrosis factor alpha (TNF-α),
prostaglandin E2 (
PGE2), and
nitric oxide (NO), was assessed using the
enzyme-linked
immunosorbent assay (ELISA) and Griess reaction. As revealed by results,
betulin inhibited the expression of pro-inflammatory mediators. In addition, the
protein expressions of
inducible nitric oxide synthase (iNOS),
cyclooxygenase-2 (COX-2),
matrix metalloproteinase (MMP-13),
thrombospondin motifs 5 (ADAMTS5),
Collagen II, and
Aggrecan were quantified using Western blot analysis. We found that
betulin could inhibit the generation of COX-2 and iNOS induced by IL-1β, indicating that
betulin has anti-inflammatory effects in chondrocytes. Furthermore,
betulin downregulates the expression of MMP-13 and ADAMTS-5 and upregulates the expression of
Collagen II and
Aggrecan, indicating that it can inhibit the degradation of the extracellular matrix. In mechanism,
betulin activated the AKT/Nrf2 pathway and inhibited the phosphorylation of p65. In in vivo studies, administration of
betulin in vivo could inhibit cartilage destruction and inflammatory progression. Therefore, these findings suggest that
betulin may alleviate IL-1β-induced OA via the AKT/Nrf2/HO-1/NF-κB signal axis, and
betulin may be a potential
drug for the treatment of OA.