Vasodilator Effect of Cassiarin A, a Novel Antiplasmodial Alkaloid from Cassia siamea, in Rat Isolated Mesenteric Artery

Abstract

Cassia siamea (Leguminosae), a small-to medium-sized tree, is one of the most commonly cultivated trees in Southeast Asia. Different parts of this plant can be used for a variety of medical purposes, giving the plant considerable medicinal potential. In traditional folk medicine, its stem bark is used as a mild, pleasant, safe purgative; a decoction of the bark is given to treat diabetes; a paste is used as a dressing for ringworm and chilblains; the roots are used as an antipyretic; and the leaves are used for the treatment of constipation, hypertension, and insomnia.1,2) A number of compounds, including barakol, emodin, b-and g-sitosterol, lupeol, luteolin, D-pinitol, chromone alkaloids, flavonoid glycosides, and a number of anthraquinones and bianthraquinones, have been isolated from Cassia siamea. 1,3,4) Although members of the genus Cassia are widely distributed in tropical and subtropical regions, where they have long been used in traditional folk medicine, particularly for the treatment of periodic fever and malaria, 5) we only recently have isolated the novel heteroaromatic alkaloid cassiarin A (Fig. 1) from the leaves of Cassia siamea. 6) This was followed a year later by the first total synthesis of cassiarin A, a process completed in eight steps from a known compound, methyl 2,4-dihydroxybenzoate.7) This alkaloid possesses an unprecedented tricyclic skeleton and exhibits potent antiplasmodial activity. 6,8,9) Although we have recently reported that some alkaloids and peptides exhibit not only antiplasmodial activity, but also vasorelaxant activity in the rat aorta, 10-12) the effect of cassiarin A on vascular tone remains unclear. We have very recently found that cassiarin A induces relaxation in the rat thoracic aorta and this was largely due to endotheliumderived nitric oxide (NO).9) However, no study has investigated the effects of cassiarin A on vascular tone in other, smaller arteries. The primary purpose of this study was therefore to test the hypothesis that cassiarin A induces in vitro vascular relaxation in rat mesenteric arteries precontracted with phenylephrine. In addition, we wanted to determine whether the vascular relaxation is endothelium dependent or whether cassiarin A acts directly upon vascular smooth muscle. MATERIALS AND METHODS Drugs and Chemicals, glibenclamide, 4-aminopyridine (4-AP), and tetraethylammonium (TEA) were all purchased from Sigma Chemical Co. (St. Louis, MO, U.S.A.). Acetylcholine chloride was from Daiichi-Sankyo Pharmaceuticals (Tokyo, Japan), 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (ODQ) was from Wako (Osaka, Japan), and iberiotoxin was from the Peptide Institute Inc. (Osaka, Japan). Drugs were dissolved in saline, except for glibenclamide [dissolved in dimethyl sulfoxide (DMSO)] and indomethacin (dissolved first in a small amount of Na 2 CO 3 0.1 M solution, then made up to the final volume with distilled water).Cassiarin A was prepared as previously reported. 6) Briefly, leaves of Cassia siamea (collected at the Purwodadi Botanical Garden, Pasuruan, Indon...

Vasorelaxant action of the total alkaloid fraction obtained from Solanum paludosum Moric. (Solanaceae) involves NO/cGMP/PKG pathway and potassium channels

“…There are few compounds potassium channel activators; cassiarin A being an example of an alkaloid among those (Matsumoto et al, 2010).…”

Echinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP-PKG-BKCa channels and reducing intracellular Ca2+ levels

“…The opening of K + channels leads to an efflux of K + that causes the cell membrane to become hyperpolarized, leading to the closure of L-type calcium channels and the reduction of intracellular Ca 2+ [15,16] . In this study, we found that BaCl 2 (an inhibitor of K IR channels) and TEA (an inhibitor of BK Ca channels) remarkably reduced the vasorelaxant effect of ECH, indicating that the K IR and BK Ca channels could be involved in this effect.…”

A Bioactivity Versus Ethnobotanical Survey of Medicinal Plants from Nigeria, West Africa

“…These are Cajanus cajan used in cancer treatment [89], Cassia alata used in the treatment of skin diseases such as ringworm, eczema, pruritis, itching, scabies, ulcers and other related diseases, Berlina grandiflora used in the treatment of gastrointestinal disorders, as well as Abrus precatorius and Cassia siamea , both used in the treatment of malaria. A dichloromethane (CH 2 Cl 2 ) fraction of the leaves of Cajanus cajan had IC 50 value 5–10 μg mL −1 , with the two constituent stilbenes, longistylins A ( 78 ) and C ( 79 ), being primarily responsible, with IC 50 values of 0.7–14.7 μM against the range of cancer cell lines [89–91]. …”