Prunellae Spica Extract Contains Antagonists for Human Endothelin Receptors

Endothelin-1 (ET-1) is a powerful vasoconstrictor that contributes to blood pressure elevation. The biological effects of ETs are mediated by two receptors, namely, endothelin type A receptor (ETAR) and endothelin type B receptor (ETBR). Chinese herbal medicines (CHM) with antagonist activity for these two receptors were screened by establishing stable clones of CHO-K1 cells expressing high levels of human ETAR and ETBR, namely CHO-ETAR and CHO-ETBR. The aqueous extract of Prunellae Spica (P1) inhibited the binding of I-125-ET-1 to ETAR and ETBR in CHO-ETAR and CHO-ETBR cells, respectively. P1 suppressed the ET-1-induced mobilization of intracellular Ca2+. Through the alcohol fractionation of P1, the antagonists of human ETAR and ETBR were found to belong to different, separable ingredients and the antagonist of ETAR is more soluble in alcohol. The two antagonists were also effective in the test on human primary cells, HASMC and HUVEC. P1 successfully prevented the development of ET-1-associated hypertension in rats without further purification. These results indicate the presence of anti-hypertensive ingredients in P. Spica extract, at least through the inactivation of ETAR and/or ETBR.