Tetrahydroxystilbene glucoside attenuated homocysteine‐upregulated endothelin receptors in vascular smooth muscle cells via the ERK1/2/NF‐κB signaling pathway

2,3,5,4’‐Tetrahydrostilbene‐2‐o‐β‐d‐glucoside (TSG) is the main active component of Polygonum multiflorum Thunb. It has effects on hypertension. However, the mechanism is unclear. Current research is devoted to exploring the mechanism of TSG improving HHcy‐induced hypertension. The mice received a subcutaneous injection of Hcy in the presence or absence of TSG for 4 weeks. Blood pressure (BP) was measured using a noninvasive tail‐cuff plethysmography method. Levels of plasma Hcy and endothelin‐1 were measured using ELISA. Rat SMA without endothelium was cultured in a serum‐free medium in the presence or absence of TSG with or without Hcy. The contractile response to sarafotoxin 6c or endothein‐1 was studied using a sensitive myography. The levels of protein were detected using Western blotting. The results showed that TSG lowered HHcy‐elevated BP and decreased levels of plasma Hcy and endothelin‐1 in mice. Furthermore, the results showed that TSG inhibited Hcy‐upregulated ET receptor expression and ET receptor‐mediated contractile responses as well as the levels of p‐ERK1/2 and p‐p65 in SMA. In vivo results further validate the in vitro results. In conclusion, TSG can decrease the levels of plasma Hcy and ET‐1 and downregulate Hcy‐upregulated ET receptors in VSMCs by inhibiting the ERK1/2/NF‐κB/ETB2 pathway to lower the BP.