Arai et al. reported the ex vivo (rat aorta) vasorelaxant activities of A. macrophylla-derived alkaloids (161–172, Fig. 14.34) (Arai et al. 2012). Various mechanisms were proposed for the vasoconstriction. Administration of 0.3 µM of
phenylephrine to the thoracic aortic rings with endothelium resulted in vasoconstriction. Vincamedine (169) resulted in a potential activity within 5–15 min, while
alstiphyllanine H (168) exhibited poor activity. Further, to understand the
involvement of endothelial cells, vasorelaxant activity was tested using
endothelium-denuded aorta (-EC rings). In the presence of a nitric oxide synthase
(NOS) inhibitor, N
G -monomethyl-L-arginine (L-NMMA, 100 µM), the relaxation
was attenuated in -EC rings, clearly indicating that the vasorelaxation was partially
mediated by the NO release from endothelial cells. Further, it was confirmed that
the vasorelaxant effect of 169 did not involve a K
+ channel.
N
N
O
O
O
O
OH
O
O
Alstiphyllanine M (167)
Alstiphyllanine I (161); R
1 = H, R
2 = R
3 = OMe, R
4 = OCOCH 3
Alstiphyllanine J (162); R
1 = R
2 = R
3 = OMe, R
4 = OCOCH 3
Alstiphyllanine K (163); R
1 = R
2 = R
3 = H, R
4 = OCOCH 3
Alstiphyllanine L (164); R
1 = H, R
2 = R
3 = OMe, R
4 = OH
Alstiphyllanine N (165); R
1 = R
2 = R
3 = H, R
4 = OH
Alstiphyllanine O (166); R
1 = R
2 = R
3 = OMe, R
4 = OH
N
N
O
O
O
Vincamedine (169)
N
N
O
O
O
O
Vincamajine-17-O-3',4',5'-trimethoxybenzoate (171)
N
+
N
HO
O
O
O
-
Alstiphyllanine H (168)
Vincamajine (170)
N
N
HO
O
O
N
N
O
O
O
O
MeO
MeO
MeO
Vincamajine-17-O-veratrate (172)
N
N
O
O
O
O
MeO
MeO
R
1
R
2
R
3
R
4
Fig. 14.34 Chemical structures of various alkaloids from A. macrophylla (161–172)
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