Brassinin Induces H2S Signals and Improves Vascular Smooth Muscle Cell Functions.

Brassinin, a sulfur-containing phytoalexin, exerts anticancer and anti-inflammatory effects. Hydrogen sulfide (H2S) is an important gasotransmitter with significant cardioprotective properties. The effects of brassinin on H2S signaling and vascular smooth muscle cell (SMC) functions remain unexplored. This study found that brassinin protected against angiotensin II (Ang II)-induced SMC dysfunctions. These effects included the attenuation of excessive cell proliferation, migration, and oxidative stress; and upregulation of smooth muscle contractile protein expressions; and down-regulation of inflammatory gene expressions. Notably, brassinin did not directly release H2S under the tested conditions; instead, it stimulated endogenous H2S synthesis in cultured SMCs by inducing the expression of cystathionine gamma-lyase (CSE), a key H2S-generating enzyme. Further mechanistic investigations revealed that brassinin may bind to the transcription factor C/EBPβ and enhance its interaction with the CSE promoter, thereby upregulating CSE transcription. In conclusion, our findings demonstrate that brassinin protects against SMC dysfunction, at least in part, by activating H2S signaling rather than acting as a direct H2S donor. These results provide new insights into the potential of brassinin as a therapeutic agent for improving vascular health and preventing cardiovascular diseases.