BackgroundOsteoarthritis (OA) is known to be associated with inflammation and cholesterol metabolism disorder. As a chronic and complex disease, uncovering its molecular mechanism and finding effective therapy with low side effects are urgent. Hydroxysafflor yellow A (HSYA) is extracted from Carthamus tinctorius L, which has extensive pharmacological effects. MethodsIn this study, Interleukin 1β (IL-1β) was used to establish the OA model in vitro, and the impacts of HSYA on the OA cell model were analyzed. We used CCK-8 to measure the cell viability and Flow Cytometry to test the apoptosis. ELISA was performed to calculate the release of inflammatory cytokines. And WB was carried out to measure the expression of collagen and cholesterol relevant proteins. We also measured the protein levels in NF-κB and PI3K/Akt/mTOR signaling pathways. ResultsThe results showed that HSYA promoted cell viability and inhibited apoptosis. And it up-regulated the expression levels of collagen II (Col-II) and Sry related HMG box-9 (SOX9) while down-regulated the expression of matrix metalloproteinase-13 (MMP13). The IL-1β induced high levels of IL-6 and TNF-α were inhibited by HSYA. Also, HSYA regulated the expression of cholesterol relevant proteins. Compared with the model group, the levels of APT-binding cassette transporter 1 (ABCA1) and cholesterol transport gene (APOA-1) were significantly elevated. However, the levels of cholesterol-processing enzymes cholesterol 25-hydroxylase (CH25H) and 25-hydroxy-cholesterol 7-alpha- hydroxylase (CYP7B1) were inhibited. Besides, HSYA inhibited the protein expression in NF-κB and PI3K/Akt/mTOR signaling pathways. ConclusionsHSYA was proved to regulate inflammatory response and cholesterol metabolism in vitro.