The Involvement of a Ca²⁺Channel Blocking Mode of Action in the Pharmacology ofAmmi visnagaFruits¹

Abstract

Based on a screening program of medicinal plants for their possible calcium antagonistic mode of action, the most active lipophilic extract of Ammi visnaga fruits (DAB 10) was fractionated by CC and investigated pharmacologically at K+ (60 mM)-depolarized guinea-pig aortic strips. Visnadin, khellin, and visnagin were identified and determined as the effective principles in this testing model with the dihydropyranocoumarin visnadin being the most active. Further selectivity tests against norepinephrine (100 microM)-induced contractions evaluated a possible pharmacological differentiation between these compounds as the furanochromones khellin and visnagin inhibited both spasms to a similar extent while visnadin's activity was significantly higher against K(+)-spasms, suggesting an involvement of a calcium channel blocking mode of action for visnadin.

Anti-inflammatory effect of visnagin in lipopolysaccharide-stimulated BV-2 microglial cells

“…1A), 4-methoxy-7-methyl-5H-furo[3,2-g][1]benzopyran-5-one (IUPAC name) is an active compound extracted from the fruits of Ammi visnaga (Kaul and Staba, 1965). Visnagin and other related active compounds, such as visnadin and khellin have vasodilator effects in vascular smooth muscle and in isolated aorta by inhibiting Ca 2+ activation and the Ca 2+ channel (Ubeda et al, 1991;Rauwald et al, 1994;Duarte et al, 1995). Visnagin also decreases blood pressure and blocks blood vessel contraction by inhibiting calcium influx into the cell (Duarte et al, 2000).…”

Neuroprotective Effect of Visnagin on Kainic Acid-induced Neuronal Cell Death in the Mice Hippocampus

“…Visnagin not only inhibited microglial and astroglial activation but also attenuated the inflammatory marker expressions concomitantly, suggesting that visnagin exerts its neuroprotective effects via an anti-inflammatory mechanism in KA model. Visnagin has been shown to relax KCl-and noradrenaline induced contractions in guinea-pig aortic strips to a similar extent [13] and this vasorelaxant effect was explained by the inhibition of Ca 2＋ entry into vascular smooth muscle cells. During excitotoxicity, glutamate concentrations increase in the synapse leads to intracellular Ca 2＋ concentration increase, activating a cell death pathway [2,3,24].…”

“…This result suggests that in addition to the anti-inflammatory effects, visnagin may also be effective during the acute damage process. First, direct inhibition of Ca 2＋ influx into neurons may be one possibility as mentioned above [13] although the underlying mechanism remains to be explored in detail. Second, the antioxydative effect of visnagin may be another candidate on co-treatment effect [37].…”

“…The fruit or its isolated active components have been used for the treatment of angina pectoris due to their peripheral and coronary vasodilator activity [10,11]. In isolated aorta, visnagin, and other related active principles present in these fruits such as visnadin and khellin inhibited vascular smooth muscle contractility, probably by acting at multiple sites to decrease the availability of Ca 2＋ required for activation [12][13][14]. Several reports have demonstrated that visnagin descents blood pressure and blocks blood vessel contraction as inhibiting calcium influx into cell [15].…”

Heterocycles [f]-Fused onto Quinolones. Synthesis of Novel Dioxo-Nethylpyrano[ 2,3-f ]- and [3,2-f ]quinoline-10-carboxylic Acids

“…The compounds of this family are well-known as antioxidants [3,4]. Some chromone derivatives, such as khellin [5] and 2,4-thiazolidenedione [6 -8], have antispasmodic and antidiabetic activities, respectively. These biological properties made this family of compounds the target of innumerous studies focusing on syntheses and structural modifications [9 -15].…”