The effects of standardized (HPLC-PDA) phytomedicine Gotas Arthur de Carvalho® on gastric acid secretion and intestinal transit in rodents

SB Bezerra1, AH Silva1, JT Pires Filho1, JCP Dantas2, TM Olinda2, RMP Siqueira2, VS Rao2, FA Santos2, LKAM Leal1. 1Federal University of Ceará, Pharmacy, Brazil, 2Federal University of Ceará, Pharmacology and Phisiology, Brazil

INTRODUCTION: Gotas Arthur de Carvalho® (GAC) is the herbal medicine produced in Brazil that is composed of tinctures: Matricaria recutita, Foeniculum vulgare and Gentiana lutea with indications as antispasmodic and digestive. Our previous works showed antispasmodic and relaxant activities of GAC on rat isolated ileum and absence of toxicity in rats treated subchronically, at a dose of 1000 mg/kg.

OBJECTIVE: Evaluate the effects of standardized GAC on the intestinal transit, gastric acid secretion and gastric volume in rodents.

METHODS AND RESULTS: The HPLC analysis allowed to quantify substances: apigenin (1,006 mg/mL), anethole/estragol (0,012 mg/mL) and gentiopicroside (1,983 mg/mL). For antisecretory activity in vivo, male Wistar rats (200-250g, n=6) fasted for 18 hours were anesthetized with xilazine/ketamin and the pylorus was ligated. Immediately after pyloric ligation, the animals were treated intraduodenally with GAC (100, 200 and 400 mg/kg), vehicle:water or cimetidine (200 mg/kg, positive control). After 4 hours, the animals were killed, the cardia was tied and the stomach was removed. Volume of supernatant of the gastric juice was measured and acidity was determined by titration with 0.1 N NaOH, using phenolphthalein as indicator. For gastric volume contents, there was no significant difference between the vehicle group (1,62 ± 0,24 mL), and the GAC groups (200: 1.70 ± 0.16 mL and 400:1.51 ± 0.26 mL). In relation to acidity, a significant difference between the control group (6.07 ± 0.50) and GAC 200 (21.25 ± 4.36 μEq[H+]/h) was noted. To determine the effect of GAC on the intestinal transit, overnight fasted male Swiss mice (25-30g, n=6) received vehicle (water, 10mL/kg, p.o.), GAC 100, 200 e 400 mg/kg (10mL/kg p.o.), or atropine (5mg/kg, i.p., positive control), 60 minutes before bethanechol (10 mg/kg, s.c.). After 60 minutes, the animals received activated charcoal (0.2 ml/10g) orally. Following 30 minutes the animals were killed, the stomach and intestine removed. We measured the total length of the intestine and distance traversed by charcoal marker from pylorus to the ileocecal junction in mm, the gastrointestinal transit was expressed in percentage in relation to total length of small intestine. Statistical analysis were carried out by ANOVA, Newman-Keuls pos test. The GAC failed to alter the normal intestinal transit, demonstrating no per se effect on gastrointestinal motility or on peristaltic activity (vehicle: 59,61 ± 3,39%; GAC 62,41 ± 3,06; 58,38 ± 3,80; 64,54 ± 3,54 %, respectively). However, in intestinal transit induced by bethanechol, GAC was capable to reduce significantly the increased gastrointestinal transit caused by cholinergic stimulant bethanechol (80, 49 ± 2,76%; GAC: 58,86 ± 4,78; 57,92 ± 2,04; 66,90 ± 3,80%).

CONCLUSION: The data indicate that GAC can effectively reduce pylorus-ligation associated increase in gastric acidity as well as the bethanechol stimulated increase in gastrointestinal transit and suggest that this phytomedicine may be useful on gastrointestinal disorders.

Financial support: CNPq, UFC, Laboratório Ravick Ltda.