Spasmogenic and spasmolytic activity of rind of Punica granatum Linn

Abstract

BackgroundRind of Punica granatum is traditionally used in treatment of abdominal cramps and various GIT disorders. So far spasmolytic activity of rind of Punica granatum has been reported using in vitro model. However, its mode of action is not explored yet. Therefore, the current work describes the possible mode of action for spasmolytic activity of methanolic extract of rind of Punica granatum (Pg. Cr). Acute toxicity study is also performed to determine its safe dose range.MethodsRind of Punica granatum was subjected to shade drying. Shade dried materials were pulverized using conventional grinder. Grinded materials were macerated in commercial grade methanol. The extract of rind of P. granatum was concentrated using a rotary evaporator. Rabbits’ jejunal preparations were mounted in organ bath containing 10 ml Tyrode’s solution, constantly aerated with carbogen gas. Pg. Cr was tested on spontaneous rabbits’ jejunal preparations in concentrations 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml. Pg. Cr was also tested on KCl (80 mM)-induced contractions in rabbits’ jejunal preparations. Since we observed spasmogenic activity for the first time, hence we also determined the effects of Pg. Cr in presence of atropine (0.03 μM). Pg. Cr was also tested in presence of 0.03 μM of loratadine HCl. Pg. Cr was also tested on barium chloride induced contractions. Calcium Concentration Response Curves (CCRCs) were constructed in the absence and presence of test samples of Pg. Cr in decalcified tissues to explore its possible mode of action. Acute toxicity screening was also performed to determine its safe dose range.ResultsPhytochemical screening revealed the presence of saponins, tannins, carbohydrates, proteins, flavonoids, saponins and steroids. However, Pg. Cr tested negative for alkaloids and triterpenoids. Pg. Cr was safe up to 100 mg/kg with its LD50 = 1305 mg/kg. Its respective EC50, in the absence and presence of atropine, were 9.7 ± 0.3 and 3.12 ± 0.45 mg/ml. In the presence of 0.02 and 0.08 μM of loratadine HCl, respective EC50 were 5.6 ± 0.4 and 2.8 ± 0.15 mg/ml. EC50 for relaxant effects on KCl-induced contractions was 8.6 ± 1 mg/ml. In the presence of 0.3 mg/ml of Pg. Cr, a right shift was observed with EC50 (log [Ca++]M) = -1.8 ± 0.09 vs. control EC50 -2.6 ± 0.01. Similarly, EC50 for verapamil (0.1 μM) was −2.4 ± 0.011vs. control EC50= -2.4 ± 0.01. The right shift of P. granatum resembled the right shift of verapamil suggesting for inhibition of voltage gated calcium channels.Conclusions P. granatum is safe up to 100 mg/kg. In low concentrations, P. granatum produced spasmogenic activity possibly through involvement of cholinergic and histaminergic receptors. The spasmolytic action may follow inhibition of the voltage gated calcium channels.

Bioactive Phytochemicals from Mercurialis spp. Used in Traditional Spanish Medicine

“…An example of this has been reported in a recent publication in which the spasmolytic and spasmogenic activity of Punica granatum Linn. were described with high and low doses of plant extracts, respectively [81]. The spasmogenic response seems to be triggered by cholinergic activation, whereas the spasmolytic effect appears to be mediated by the blockade of voltage gated calcium channels.…”

Pomegranate Mesocarp against Colitis-Induced Visceral Pain in Rats: Effects of a Decoction and Its Fractions

“…Moreover, ellagic acid was also able to significantly decrease the abdominal irritation induced by acetic acid in mice [ 11 ]. Pomegranate possesses antioxidant [ 12 , 13 ], antimicrobial, and prebiotic effects [ 14 ], as well as spasmogenic and spasmolytic activities [ 15 ]. Recently, the potential beneficial properties of pomegranate in several gastrointestinal diseases have become increasingly interesting.…”

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“…To determine the spasmolytic activity of DCD-684 by its interaction on different receptors and/or with Ca 2+ channels, various agonists were employed in jejunum tissue. It is well-documented that KCl (80mM) induces smooth muscle contractions via membrane depolarization causing Ca 2+ influx through L-type voltage-dependent Ca 2+ channels without receptor stimulation (Cortes et al, 2006;Godfraind et al, 1986;Hajagos-Tóth et al, 2009) and were blocked by verapamil, a reputable calcium channel blocker (Ali et al, 2017). Hence, substances inhibiting such contractions may be considered as blocker of calcium influx (Godfraind et al, 1986).…”

“…The GIT is also richly occupied with histaminergic receptors (Ali et al, 2017) and histamine plays a vital role in the regulation of gastric acid and ion secretion, gastric mucosal defense and intestinal motility (Fabisiak et al, 2017). It stimulates the contractile response by increasing chloride secretion by colonic epithelium by the activation of H 1 receptors residing in the smooth muscles.…”