Pharmacological basis for the medicinal use of black pepper and piperine in gastrointestinal disorders.
Dried fruits of Piper nigrum (black pepper) are commonly used in gastrointestinal disorders. The aim of this study was to rationalize the medicinal use of pepper and its principal alkaloid, piperine, in constipation and diarrhea using in vitro and in vivo assays. When tested in isolated guinea pig ileum, the crude extract of pepper (Pn.Cr) (1–10 mg/mL) and piperine (3–300 μM) caused a concentration-dependent and atropine-sensitive stimulant effect. In rabbit jejunum, Pn.Cr (0.01–3.0 mg/mL) and piperine (30–1,000 μM) relaxed spontaneous contractions, similar to loperamide and nifedipine. The relaxant effect of Pn.Cr and piperine was partially inhibited in the presence of naloxone (1 μM) similar to that of loperamide, suggesting the naloxone-sensitive effect in addition to the Ca(2+) channel blocking (CCB)-like activity, which was evident by its relaxant effect on K+ (80 mM)-induced contractions. The CCB activity was confirmed when pretreatment of the tissue with Pn.Cr (0.03–0.3 mg/mL) or piperine (10–100 μM) caused a rightward shift in the concentration–response curves of Ca(2+), similar to loperamide and nifedipine. In mice, Pn.Cr and piperine exhibited a partially atropine-sensitive laxative effect at lower doses, whereas at higher doses it caused antisecretory and antidiarrheal activities that were partially inhibited in mice pretreated with naloxone (1.5 mg/kg), similar to loperamide. This study illustrates the presence of spasmodic (cholinergic) and antispasmodic (opioid agonist and Ca(2+) antagonist) effects, thus providing the possible explanation for the medicinal use of pepper and piperine in gastrointestinal motility disorders.
Mehmood
Malik Hassan
MH
Natural Product Research Division, Department of Biological and Biomedical Sciences, Aga Khan University Medical College, Karachi, Pakistan.
Gilani
Anwarul Hassan
AH
D000470:Alkaloids / Q000008:administration & dosage*; D000818:Animals; D000930:Antidiarrheals; D052117:Benzodioxoles / Q000008:administration & dosage*; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D018678:Cholinergic Agents / Q000008:administration & dosage; D003248:Constipation / Q000188:drug therapy; D003967:Diarrhea / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005767:Gastrointestinal Diseases / Q000188:drug therapy*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects; D054368:Laxatives; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D008517:Phytotherapy; D029222:Piper nigrum / Q000737:chemistry*; D010880:Piperidines / Q000008:administration & dosage*; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage*; D011817:Rabbits; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology
D000470:Alkaloids; D000930:Antidiarrheals; D052117:Benzodioxoles; D002121:Calcium Channel Blockers; D018678:Cholinergic Agents; D054368:Laxatives; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011957:Receptors, Opioid; D009270:Naloxone; C008922:piperine