Hydroxysafflor yellow A inhibits lipopolysaccharide-induced proliferation and migration of vascular smooth muscle cells via Toll-like receptor-4 pathway

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is closely associated with early vascular hyperplasic lesions. Toll-like receptor (TLR)-4 is a pathogen pattern recognition receptor expressed on VSMCs, and can be activated by lipopolysaccharide. Activated TLR-4 plays a promoting role in VSMCs proliferation and migration through the downstream signaling pathways including Rac1/Akt. Hydroxysafflor yellow A (HSYA) is the main component of the safflower yellow pigments, which has long been used for the treatment of cardiovascular diseases in traditional Chinese medicine. However, the effect of HSYA on VSMC proliferation and migration remains unknown. In the present study, we showed that HYSA could inhibit LPS-induced VSMCs proliferation and migration, accompanied by the downregulated levels of several key pro-inflammatory cytokines, including TNF-alpha, IL-6, and IL-8. We further showed that HYSA inhibited LPS-induced upregulation of TLR-4 expression as well as the activation of Rac1/Akt pathway, suggesting that HSYA inhibits LPS-induced VSMCs proliferation and migration, partly at least, via inhibition of TLR-4/Rac1/Akt pathway. Accordingly, HSYA may be used as a promising agent for prevention and treatment of vascular hyperplasic disorders.