Cardio-selective inhibitory effect of the betel nut extract: possible explanation.

Chewing of betel nut, the seed of Areca catechu, is associated with a host of physical and psychological effects while it is also traditionally used in constipation and hypertension. In this study, we report the cardio-selective cholinomimetic activity of the betel nut crude extract (Ac.Cr). Ac.Cr, that tested positive for saponins, tannins, phenols, alkaloids and terpenes, exhibited dose-dependent atropine-sensitive inhibition of isolated guinea-pig atrial contractility with an EC50 value of 0.93 microg/ml (0.57-1.51, 95% CI). In rabbit jejunum, Ac.Cr showed atropine-sensitive spasmogenicity with an EC50 of 7.31 microg/ml (5.41-9.88, 95% CI) showing that it is around 8 times more potent in the cardiac than the intestinal preparation. Both carbachol and physostigmine exhibited acetylcholine-like stimulant activity in jejunum with the latter being more potent in jejunum than in atrial tissues. Activity-directed fractionation of Ac.Cr yielded fractions with similar cholinergic activity in atria and jejunum except the aqueous fraction being 6 times more potent in the atria. Arecoline, the known betel nut compound with cholinergic activity showed similar potency in both tissues while catechin and tannic acid exhibited intestinal spasmolytic effect but were inactive in atria. The results show the cardio-selective inhibitory effect of Ac.Cr which might possibly be due to selective gut-spasmolytic behaviour of catechin and tannic acid thus reducing the cholinomimetic activity of Ac.Cr in the gut though the preferential binding of the constituents of betel nut extract at muscarinic receptor subtypes in heart cannot be ignored.

Studies on the antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities of the Carum copticum seed extract.

This study describes the antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities of the aqueous-methanolic extract of Carum copticum Benth. seeds (CSE) to rationalize some of its traditional uses. CSE (3-100 mg/kg) caused a dose-dependent fall in arterial blood pressure in anaesthetized rats. In isolated rabbit aorta and jejunum preparations, CSE (0.1-3.0 mg/ml) caused an inhibitory effect on the K+-induced contractions. The calcium channel blocking (CCB) effect was confirmed when CSE shifted the Ca2+ dose-response curves (DRCs) to right similar to verapamil. In isolated guinea-pig tracheal preparations, it caused inhibition of carbachol and K+-induced bronchoconstriction at 0.1-1.0 mg/ml as well as shifted the dose-response curves (DRCs) of carbachol and histamine to the right with suppression of maximum response suggestive of non-specific bronchodilator effect mediated possibly through CCB. Pretreatment of rats with CSE (500 mg/kg orally for 2 days at 12 h intervals) prevented paracetamol (640 mg/kg) and CCl4 (150 ml/kg)-induced rise in serum alkaline phosphatase (ALP) and aminotransferases (AST and ALT). The same dose of CSE was able to prevent the CCl4-induced prolongation in pentobarbital-induced sleeping time in mice confirming its hepatoprotectivity. These results indicate the presence of calcium antagonist(s) in Carum copticum seeds and thus provides sound mechanistic basis for some of their folkloric uses.

Presence of calcium antagonist activity explains the use of Syzygium samarangense in diarrhoea.

Syzygium samarangense (Family; Myrtaceae) or 'makopa', as it is commonly known, is native to Malaysia, some islands of Indonesia and to Far East in general. This study was undertaken to rationalize the use of this plant in hypermotility states of the gut. The hexane extract of S. samarangense (Ss.Hex) was found to dose-dependently (10-3000 microg/mL) relax the spontaneously contracting isolated rabbit jejunum. When tested for a possible calcium channel blocking (CCB) activity, the extract (10-1000 microg/mL) relaxed the high K+-induced contractions and also decreased the Ca++ dose-response curves in a dose-dependent manner (30-100 microg/mL), confirming the CCB activity. Four flavonoids isolated from the hexane extract were tested for a possible spasmolytic activity. All flavonoids, identified as: 2'-hydroxy-4',6'-dimethoxy-3'-methylchalcone (SS1), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (SS2), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (SS3) and 7-hydroxy-5-methoxy-6,8-dimethylflavanone (SS4), showed dose-dependent (10-1000 microg/mL) spasmolytic activity with SS2 being the most potent. These results indicate that the presence of compounds with spasmolytic and calcium antagonist activity may be responsible for the medicinal use of the plant in diarrhoea.