Hydroxysafflor Yellow A Regulates Inflammation and Oxidative Stress by Suppressing the HIF-1α/JAK/STAT3 Signaling Pathway to Attenuate Osteoarthritis

Abstract

Hydroxysafflor yellow A is extracted from Carthamus tinctorius L., Asteraceae, and has extensive pharmacological properties. In this study, interleukin-1 beta was used to establish the osteoarthritis model in vitro, and the impacts of hydroxysafflor yellow A on the cell model were analyzed. CCK8 was used to measure cell viability, and flow cytometry was used to evaluate apoptosis and reactive oxygen species. An enzyme-linked immunosorbent assay was performed to calculate the release of inflammatory cytokines and oxidative stress index. Western blotting was performed to measure the expression of collagen-related proteins. The protein levels in the HIF-1α/JAK/STAT3 signaling pathway were also measured. The results showed that hydroxysafflor yellow A promoted cell viability and inhibited apoptosis and oxidative stress. In addition, quinochalcone C-glycoside upregulated the expression of collagen II and Sry-related HMG box-9, while downregulating the expression of matrix metalloproteinase-13. Interleukin-1 beta induced high levels of interleukin-6 and tumor necrosis factor-α that were inhibited by hydroxysafflor yellow A. Meanwhile, hydroxysafflor yellow A inhibited the interleukin-1 beta–induced high levels of reactive oxygen species and malondialdehyde and enhanced the interleukin-1 beta–induced low levels of superoxide dismutase and glutathione peroxidase. Furthermore, hydroxysafflor yellow A downregulated the mRNA expression of HIF-1α, JAK, STAT3, and interleukin-6 as well as the protein expression of HIF-1α, p-JAK, and p-STAT3. The results suggest that hydroxysafflor yellow A inhibited the JAK/STAT3 signaling pathways by inhibiting HIF-1α. Therefore, hydroxysafflor yellow A regulates the inflammatory response and oxidative stress in vitro.Graphical abstract