Natural Product Research Division, Department of Biological and Biomedical Sciences, Aga Khan University Medical College, Karachi, Pakistan.
J Med Food. 2010 Oct;13(5):1086-96. doi: 10.1089/jmf.2010.1065.
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.
胡椒（黑胡椒）的干果实常用于胃肠道疾病。本研究旨在通过体外和体内试验来合理化胡椒及其主要生物碱胡椒碱在便秘和腹泻中的药用用途。在分离的豚鼠回肠中，胡椒粗提取物（Pn.Cr）（1-10mg/mL）和胡椒碱（3-300μM）以浓度依赖的方式引起阿托品敏感的刺激作用。在兔空肠中，Pn.Cr（0.01-3.0mg/mL）和胡椒碱（30-1000μM）松弛自发性收缩，类似于洛哌丁胺和硝苯地平。在存在纳洛酮（1μM）的情况下，Pn.Cr 和胡椒碱的松弛作用部分被抑制，类似于洛哌丁胺，表明存在阿片受体敏感作用，此外还有钙通道阻断（CCB）样活性，这可以通过其对 K+（80mM）诱导的收缩的松弛作用来证明。当组织用 Pn.Cr（0.03-0.3mg/mL）或胡椒碱（10-100μM）预处理时，CCB 活性得到确认，导致 Ca（2+）浓度-反应曲线发生右移，类似于洛哌丁胺和硝苯地平。在小鼠中，Pn.Cr 和胡椒碱在较低剂量下表现出部分阿托品敏感的通便作用，而在较高剂量下，它引起抗分泌和抗腹泻作用，在预先用纳洛酮（1.5mg/kg）预处理的小鼠中被部分抑制，类似于洛哌丁胺。本研究说明了存在痉挛（胆碱能）和抗痉挛（阿片受体激动剂和钙拮抗剂）作用，从而为胡椒和胡椒碱在胃肠道动力障碍中的药用用途提供了可能的解释。
