dendrobine and Inflammation

Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and cartilage degradation. Dendrobine (DEN) is reported to inhibit inflammation and oxidative stress in some diseases, but its role in chondrocyte senescence and OA progress has not yet been elucidated. Our study aimed to explore the protective effects of DEN on OA both in vitro and in vivo. We found that DEN inhibited extracellular matrix (ECM) degradation and promoted ECM synthesis. Meanwhile, DEN inhibited senescence-associated secretory phenotype (SASP) factors expression and senescence phenotype in IL-1β-treated chondrocytes. Furthermore, DEN improved mitochondrial function and reduced the production of intracellular reactive oxygen species (ROS). Also, DEN suppressed IL-1β-induced activation of the NF-κB pathway. Further, using NAC (ROS inhibitor), we found that DEN might inhibit NF-κB cascades by reducing ROS. Additionally, X-ray, micro-CT, and histological analyses in vivo demonstrated that DEN significantly alleviated cartilage inflammation, ECM degradation, and subchondral alterations in OA progression. In conclusion, DEN inhibits SASP factors expression and senescence phenotype in chondrocytes and alleviated the progression of OA via the ROS/NF-κB axis, which provides innovative strategies for the treatment of OA.

Topics: Cells, Cultured; Cellular Senescence; Chondrocytes; Humans; Inflammation; Interleukin-1beta; NF-kappa B; Osteoarthritis; Reactive Oxygen Species

Topics: Alkaloids; Antioxidants; Apoptosis; HaCaT Cells; Humans; Hydrogen Peroxide; Inflammation; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Oxidative Stress; Oxidoreductases; Reactive Oxygen Species; Signal Transduction

Gestational diabetes mellitus (GDM) is a common disease in pregnant women with a prevalence from 1.4% to 14% based on the population studied. The number of patients with GDM is increasing annually, and yet, the treatment for GDM remains limited. In this study, we aimed to explore the potential of dendrobine against GDM. For this purpose, a genetic mouse model of GDM was established. GDM mice were orally administered with 20 mg/kg dendrobine daily from the beginning of pregnancy to delivery. It was found that dendrobine significantly ameliorated the symptoms of GDM, as evidenced by reduced maternal body-weight and blood glucose levels, as well as increased insulin levels and insulin sensitivity in GDM mice. Dendrobine also remarkably attenuated the impairments to offspring, such as decreased birth-weight and birth size. Moreover, dendrobine reduced the secretion of inflammatory cytokines by T helper 17 (Th17) cells, including interleukin-1β, interleukin-6, tumour necrosis factor-α and interleukin-17. Furthermore, we found that dendrobine also reduced the population of Th17 cells in GDM mice. In conclusion, dendrobine could effectively alleviate GDM in mice and might serve as a potential therapeutic drug candidate for GDM patients.

Topics: Alkaloids; Animals; Diabetes, Gestational; Female; Inflammation; Mice; Mice, Inbred C57BL; Pregnancy; Th17 Cells