neobavaisoflavone and Hypoxia

Osteoarthritis (OA) is a chronic inflammatory joint disease. There have been some studies on the treatment of OA with traditional Chinese medicine (TCM). Neobavaisoflavone (NBIF) is an isoflavone isolated from TCM Psoralea corylifolia L (also called 'Buguzhi') and shows anti-inflammatory effects. This study aims to explore the potential role of NBIF in treating OA. The rat chondrocytes were dealt with interleukin-1beta (IL-1β) for inducing an in-vitro OA model and a rat OA model was established by medial collateral ligament resection. Followed by NBIF treatment, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry were performed to evaluate chondrocyte proliferation and apoptosis. The expression of inflammatory factors and oxidative stress factors in chondrocyte medium and rat serum was tested by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining and Safranin O-Fast Green staining were carried out to examine the histopathological changes in knee joints. Caspase-3, nuclear factor-kappaB (NF-κB), and hypoxia-inducible factor-2alpha (HIF-2α) expressions were monitored by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, and/or immunohistochemistry. As indicated by the results, NBIF mitigated cartilage matrix degradation and chondrocyte apoptosis in the OA rat model. NBIF hampered IL-1β-mediated cell viability inhibition, apoptosis, inflammatory reactions, and oxidative stress of chondrocytes. Moreover, NBIF suppressed NF-κB phosphorylation and HIF-2α expression. HIF-2α overexpression induced inflammation, oxidative stress, and apoptosis in chondrocytes, while NBIF reversed HIF-2α overexpression-caused chondrocyte damage. Overall, NBIF had antiapoptotic, anti-inflammatory, and antioxidative stress effects in OA models by impeding NF-κB/HIF-2α axis, suggesting that NBIF has potential therapeutic effects in OA.

Topics: Animals; Anti-Inflammatory Agents; Basic Helix-Loop-Helix Transcription Factors; Collateral Ligaments; Hypoxia; Inflammation; Interleukin-1beta; Isoflavones; NF-kappa B; Osteoarthritis; Rats