New vasorelaxant indole alkaloids, villocarines A–D from Uncaria villosa

Abstract

Villocarines A-D (1-4), four new indole alkaloids have been isolated from the leaves of Uncaria villosa (Rubiaceae) and their structures were elucidated by 2D NMR methods and chemical correlations. Villocarine A (1) showed vasorelaxation activity against rat aortic ring and showed inhibition effect on vasocontraction of depolarized aorta with high concentration potassium, and also inhibition effect on phenylephrine (PE)-induced contraction in the presence of nicardipine in a Ca(2+) concentration-dependent manner. The vasorelaxant effect by 1 might be attributed mainly to inhibition of calcium influx from extracellular space through voltage-dependent calcium channels (VDC) and/or receptor-operated Ca(2+)-channels (ROC), and also partly mediated through the increased release of NO from endothelial cells and opening of voltage-gated K(+)-channels.

Medicinal uses, phytochemistry and pharmacology of the genus Uncaria

“…These results suggested that rhynchophylline (32) and isorhynchophylline (40) exert antihypertensive activities by inhibiting of the vasomotor center, sympathetic nerves and ganglia and blocking of L-type decrease of calcium (Ca 2 þ ) channels (Song et al, 2000;Shi et al, 1989;Wang and Li, 1998;Zhang et al, 2004;Li et al, 2013); Villocarine A (10) and geissoschizine methyl ether (11) acted on rat aortic ring to show vasorelaxation activities. The underlying mechanisms of villocarine A (10) mainly described as follows: (i) inhibited calcium influx from extracellular space through voltage-dependent calcium channels and/or receptor-operated Ca 2 þ -channels; (ii) promoted the release of NO from endothelial cells; (iii) stimulated the opening of voltage-gated K þ -channels (Matsuo et al, 2011). Different from villocarine A (10), geissoschizine methyl ether (11) affected aortic ring through endothelial dependency with nitric oxide at low concentrations of 0.1-3 mM and endothelial independency with Ca 2 þ channel blockade at higher concentrations of 10-100 mM (Yuzurihara et al, 2002).…”

Plant-Based Indole Alkaloids: A Comprehensive Overview from a Pharmacological Perspective

“…Villocarine showed slightly less vascular relaxation activity in aortic tissues with no endothelium. Villocarine A was isolated from Uncaria villosa ( Figure 11 ) [ 39 ].…”

Alkaloids from the hook-bearing branch ofUncariarhynchophyllaand their neuroprotective effects against glutamate-induced HT22 cell death

“…The structures of 1 – 4 were elucidated by 1D and 2D NMR, UV, MS, and circular dichroism (CD) techniques, and 5 – 11 were identified by comparing their 1 H NMR, UV, MS, and CD data with reported values [8–10]. Compound 1 was confirmed as a new alkaloid, 4-geissoschizine N -oxide methyl ether (1) , together with the following 10 known alkaloids 3-epi-geissoschizine methyl ether (2) isolated from U. rhynchophylla for the first time [11], geissoschizine methyl ether (3) , 4-hirsuteine N -oxide (4) , hirsuteine (5) , hirsutine (6) , 3α-dihydro-cadambine (7) , 3β-isodihydro-cadambine (8), cadambine (9) , strictosamide (10) , and akuammigine (11) . The neuroprotection of 1 – 9 against glutamate-induced HT22 cell death was assayed for the first time.…”