Antidiarrhoeal, antisecretory and antispasmodic activities of Matricaria chamomilla are mediated predominantly through K+-channels activation

Malik Hassan Mehmood, Siraj Munir, Uzair Ali Khalid, Mudassir Asrar, Anwarul Hassan Gilani

Matricaria chamomilla commonly known as "Chamomile" (Asteraceae) is a popular medicinal herb widely used in indigenous system of medicine for a variety of ailments. However, there is no detailed study available showing its effectiveness in hyperactive gut disorders like, abdominal colic and diarrhoea. This study was designed to determine the pharmacological basis for the folkloric use of M. chamomilla in diarrhoea. The crude aqueous-methanolic extract of M. chamomilla (Mc.Cr) was studied for its protective effect in mice against castor oil-induced diarrhoea and intestinal fluid accumulation. The isolated rabbit jejunum was selected for the in-vitro experiments using tissue bath assembly coupled with PowerLab data acquisition system. Oral administration of Mc.Cr to mice at 150 and 300 mg/kg showed marked antidiarrhoeal and antisecretory effects against castor oil-induced diarrhoea and intestinal fluid accumulation, simultaneously, similar to the effects of cromakalim and loperamide. These effects of plant extract were attenuated in animals pretreated with K(+) channel antagonist, glibenclamide (GB) or 4-aminopyridine (4-AP). When tested in isolated rabbit jejunum, Mc.Cr caused a dose-dependent (0.3-3 mg/ml) relaxation of spontaneous and low K(+) (25 mM)-induced contractions, while it exhibited weak inhibitory effect on high K(+) (80 mM). The inhibitory effect of Mc.Cr on low K(+)-induced contractions was partially inhibited in the presence of GB, while completely blocked by 4-AP. Cromakalim, an ATP-sensitive K(+) channel opener, caused complete relaxation of low K(+)-induced contractions with little effect on high K(+). Pretreatment of tissues with GB blocked the inhibitory effects of cromakalim on low K(+), while the presence of 4-AP did not alter the original effect. Verapamil, a Ca(++) channel antagonist, caused complete relaxation of both low and high K(+)-induced contractions with similar potency. The inhibitory effect of verapamil was insensitive to GB or 4-AP. When assessed for Ca(++) antagonist like activity, Mc.Cr at high concentrations caused rightward shift in the Ca(++) concentration-response curves with suppression of the maximum response, similar to the effect of verapamil, while cromakalim did not show similar effect. This study indicates that Matricaria chamomilla possesses antidiarrhoeal, antisecretory and antispasmodic activities mediated predominantly through K(+)-channels activation along with weak Ca(++) antagonist effect.