T. Ohshima et al., PHEOPHORBIDE A, A POTENT ENDOTHELIN RECEPTOR ANTAGONIST FOR BOTH ET(A) AND ET(B) SUBTYPES, Chemical and Pharmaceutical Bulletin, 42(10), 1994, pp. 2174-2176
Many crude drugs were screened for their capacity to inhibit the bindi
ng of endothelin-1 (ET-1) to ET receptors; several crude drugs showed
significant binding inhibitory activity. Pheophorbide a (1), a potent
non-peptide ET receptor antagonist, was isolated from Altemisiae capil
laris Flos (''Inchinko'' in Japanese), which has been utilized as a re
medy for hepatitis in Oriental medicine. In receptor binding experimen
ts, compound 1 inhibited ET-1 binding specifically to both the ET(A) r
eceptor (ET(A)R) and ET(B) receptor (ET(B)R), with IC50 values of 8.0
x 10(-8) and 2.1x10(-7)M, respectively. Thus, compound 1 is an ET-1 bi
nding inhibitor; however, it exhibited no affinity for the other recep
tors of angiotensin IT and atrial natriuretic peptide. We also evaluat
ed the inhibitory activity of porphyrin compounds, and found that some
exhibited moderate activity.