Dual mechanisms of anti-muscarinic and Ca++ antagonistic activities to validate the folkloric uses of Cyperus niveus Retz. as antispasmodic and antidiarrheal

• Published in: Journal of ethnopharmacology 2018-03, Vol.213, p.138-148
• Main Authors: Aleem, Ambreen, Janbaz, Khalid Hussain
• Format: Article
• Language: English
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2017.11.006

Cyperus species are famous for their traditional uses and very commonly used for their anti-spasmodic and anti-diarrheal activities. Cyperus niveus Retz. is used in local traditional system of medicine in Pakistan to treat diarrhea and emesis. The aim of the study was to validate the traditional uses and to provide the possible mechanisms for the medicinal use of Cyperus niveus Retz. as anti-spasmodic, anti-diarrheal and anti emetic. The in-vivo studies of anti-diarrheal, charcoal meal GI transit test and anti-emetic activities were conducted in rats, mice and chicks respectively, while isolated tissues of rabbit's jejunum and rat's ileum were used for in-vitro experiments. Phytochemical analysis was also undertaken. The phytochemical study of hydro-ethanolic extract of Cyperus niveus Retz. showed the presence of flavonoids, phenols, alkaloids, tannins, saponins and glycosides. Cn. Cr caused significant inhibition of castor oil-induced diarrhea in rats (300,500 & 700mg/kg) using loperamide (10mg/kg, p.o) as standard. Cn. Cr also significantly decreased the motility in charcoal meal GI transit test at 100–200mg/kg in mice, using atropine (3.0mg/kg) as positive control. In jejunum tissue, Cn. Cr relaxed carbachol(1µM) and K+(80mM)-induced contractions, similar to the effect of dicyclomine. Pre-incubation of isolated rat ileum tissues with Cn. Cr (0.1mg/mL) caused the corresponding shift of CCh concentration response curve (CRC) to right without decrease in max. response whereas at the concentration of 0.3mg/mL caused the rightward nonparallel shift with max. response suppression, similar to dicyclomine. Antimuscarinic effect was further confirmed when prior administration of Cn. Cr (0.1, 0.3 and 1mg/mL) caused concentration dependent inhibition of induced contractions of carbachol, comparable to atropine (1µM). To confirm the Ca2+ channel blocking (CCB), the rabbit jejunum was pre-incubated with Cn. Cr (0.3 & 1.0mg/mL), produced a shift in CRCs of calcium toward right with decrease in the maximum response at next concentration, similar to that of dicyclomine. The organic fraction of Cyperus niveus Retz. (Cn. Dcm) showed Ca2+ antagonist and anticholinergic activities with higher potency against K+(80mM) induced contractions, like verapamil, while aqueous fraction (Cn. Aq) relaxed only carbachol(1µM) induced contractions with no prominent effect on K+ (80mM)-contractions even at the higher concentration of 10mg/mL, similar to atropine. Cn. Cr also showed signi