Pharmacological basis for the medicinal use of psyllium husk (Ispaghula) in constipation and diarrhea

Background: The objective of this study was to determine the pharmacological basis of the medicinal use of psyllium husk (Ispaghula) in gastrointestinal motility disorders. Methods: In-vivo studies were conducted on mice, and isolated rabbit jejunum and guinea-pig ileum were used in in-vitro experiments. Results: The crude extract of Ispaghula (Po.Cr) had a laxative effect in mice at 100 and 300 mg/kg, which was partially sensitive to atropine or SB203186 (5-HT₄ antagonist). At higher doses (500 and 1,000 mg/kg), Po.Cr had antisecretory and antidiarrheal activity. In guinea-pig ileum, Po.Cr (1-10 mg/ml) had a stimulatory effect, which was partially sensitive to atropine or SB203186. In rabbit jejunum, Po.Cr had a partially atropine-sensitive stimulatory effect followed by relaxation at 10 mg/ml. The relaxation was inhibited by the presence of l-NAME, a nitric oxide (NO) synthase inhibitor, or methylene blue, a guanylyl cyclase inhibitor. Similarly, the relaxant effect of Po.Cr on K⁺ (80 mM)-induced contractions, was attenuated in the presence of l-NAME or methylene blue. Activity-directed fractionation of Po.Cr revealed that the gut stimulatory and inhibitory constituents were widely distributed in the aqueous and organic fractions. Conclusion: This study demonstrates that Ispaghula has a gut-stimulatory effect, mediated partially by muscarinic and 5-HT₄ receptor activation, which may complement the laxative effect of its fiber content, and a gut-inhibitory activity possibly mediated by blockade of Ca²⁺ channels and activation of NO-cyclic guanosine monophosphate pathways. This may explain its medicinal use in diarrhea. It is, perhaps, also intended by nature to offset an excessive stimulant effect.