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Inhibitory effect of the herbal antidepressant St. John’s wort (Hypericum perforatum) on rat gastric motility

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Abstract

St. John’s wort (Hypericum perforatum) is a highly popular and effective herbal antidepressant that clinically interacts with a number of conventional drugs. Because alterations in gastric emptying can cause pharmacokinetic interactions, in the present study we evaluated the effect of a standardized extract prepared from the flowering tops of Hypericum perforatum (SJW extract) on rat gastric motility. Orally administered SJW extract delayed gastric emptying in vivo. In vitro studies showed that SJW extract was significantly more active in inhibiting acetylcholine (or prostaglandin E2)-induced contractions than electrical field stimulation (EFS)-induced contractions. The effect of SJW extract on EFS-induced contractions was unaffected by drugs that inhibit intrinsic inhibitory nerves or by tachykinin antagonists, but it was reduced by the 5-hydroxytryptamine antagonist methysergide. The inhibitory effect of SJW extract on acetylcholine-induced contractions was reduced by the sarcoplasmic reticulum Ca2+-ATPase inhibitor cyclopiazonic acid, but not by the L-type Ca2+ channel blocker nifedipine or by methysergide. Among the chemical constituents of SJW extract tested, hyperforin and, to a lesser extent, the flavonoids kaempferol and quercitrin, inhibited acetylcholine-induced contractions. It is concluded that SJW has a direct inhibitory effect on smooth muscle and could also possibly modulate gastric neurotransmission. If extended to humans, the inhibitory effect of SJW extract on gastric emptying in vivo could contribute, at least in part, to the clinical pharmacokinetic interactions between conventional medicines and this herbal antidepressant.

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Abbreviations

SJW extract:

standardized extract prepared from the flowering tops of Hypericum perforatum

EFS:

electrical field stimulation

L-NAME:

NG-nitro-L-arginine methyl ester

DMSO:

dimethyl sulphoxide

hCGRP 1–29:

VIP antagonist [Ac-Tyr1,D-Phe2]GRF 1–29 amide

Prostaglandin E2 :

PGE2

References

  • Abdel-Salam OM (2005) Anti-inflammatory, antinociceptive, and gastric effects of Hypericum perforatum in rats. Sci World J 5:586–595

    Google Scholar 

  • Blumenthal M, Ferrier KLG, Cavaliere C (2006) Total sales of herbal supplements in United States show steady growth. HerbalGram 71:64–66

    Google Scholar 

  • Borrelli F, Capasso F, Capasso R, Ascione V, Aviello G, Longo R, Izzo AA (2006) Effect of Boswellia serrata on intestinal motility in rodents: inhibition of diarrhoea without constipation. Br J Pharmacol 148:553–560

    Article  PubMed  CAS  Google Scholar 

  • Buchholzer ML, Dvorak C, Chatterjee SS, Klein J (2002) Dual modulation of striatal acetylcholine release by hyperforin, a constituent of St. John’s wort. J Pharmacol Exp Ther 301:714–719

    Article  PubMed  CAS  Google Scholar 

  • Butterweck V, Korte B, Winterhoff H (2001) Pharmacological and endocrine effects of Hypericum perforatum and hypericin after repeated treatment. Pharmacopsychiatry 34:S2–S7

    Article  PubMed  CAS  Google Scholar 

  • Butterweck V, Nahrstedt A, Evans J, Hufeisen S, Rauser L, Savage J, Popadak B, Ernsberger P, Roth BL (2002) In vitro receptor screening of pure constituents of St. John’s wort reveals novel interactions with a number of GPCRs. Psychopharmacology 162:193–202

    Article  PubMed  CAS  Google Scholar 

  • Capasso R, Borrelli F, Capasso F, Mascolo N, Izzo AA (2004) Inhibitory effect of the antidepressant St. John’s wort (Hypericum perforatum) on rat bladder contractility in vitro. Urology 64:168–172

    Article  PubMed  Google Scholar 

  • Capasso R, Borrelli F, Montanaro V, Altieri V, Capasso F, Izzo AA (2005) Effects of the antidepressant St. John’s wort (Hypericum perforatum) on rat and human vas deferens contractility. J Urol 173:2194–2197

    Article  PubMed  CAS  Google Scholar 

  • Capasso R, Borrelli F, Capasso F, Siebert DJ, Stewart DJ, Zjawiony JK, Izzo AA (2006) The hallucinogenic herb Salvia divinorum and its active ingredient salvinorin A inhibit enteric cholinergic transmission in the guinea-pig ileum. Neurogastroenterol Motil 18:69–75

    Article  PubMed  CAS  Google Scholar 

  • De Smet PA (2002) Herbal remedies. N Engl J Med 347:2046–2056

    Article  PubMed  Google Scholar 

  • Di Carlo G, Borrelli F, Ernst E, Izzo AA (2001) St. John’s wort: Prozac from the plant kingdom. Trends Pharmacol Sci 22:292–297

    Article  PubMed  Google Scholar 

  • El-Salhy M (2001) Gastric emptying in an animal model of human diabetes type 1: relation to endocrine cells. Acta Diabetol 38:139–144

    Article  PubMed  CAS  Google Scholar 

  • Ernst E (1999) Second thoughts about safety of St. John’s wort. Lancet 354:2014–2016

    Article  PubMed  CAS  Google Scholar 

  • Gambarana C, Ghiglieri O, Tolu P, De Montis MG, Giachetti D, Bombardelli E (2001) Pharmacological and endocrine effects of Hypericum perforatum and hypericin. Pharmacopsychiatry 34:S2–S7

    Article  Google Scholar 

  • Gershon MD, Tack J (2007) The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 132:397–414

    Article  PubMed  CAS  Google Scholar 

  • Gilani AH, Khan AU, Subhan F, Khan M (2005) Antispasmodic and bronchodilator activities of St. John’s wort are putatively mediated through dual inhibition of calcium influx and phosphodiesterase. Fund Clin Pharmacol 19:695–705

    Article  CAS  Google Scholar 

  • Grasa L, Rebollar E, Arruebo MP, Plaza MA, Murillo MD (2004) The role of Ca2+ in the contractility of rabbit small intestine in vitro. J Physiol Pharmacol 55:639–650

    PubMed  CAS  Google Scholar 

  • Hu Z, Yang X, Ho PC, Chan SY, Heng PW, Chan E, Duan W, Koh HL, Zhou S (2005) Herb-drug interactions: a literature review. Drugs 65:1239–1282

    Article  PubMed  CAS  Google Scholar 

  • Hu ZP, Yang XX, Chan SY, Xu AL, Duan W, Zhu YZ, Sheu FS, Boelsterli UA, Chan E, Zhang Q, Wang JC, Ee PL, Koh HL, Huang M, Zhou SF (2006) St. John’s wort attenuates irinotecan-induced diarrhea via down-regulation of intestinal epithelial apoptosis. Toxicol Appl Pharmacol 216:225–237

    Article  PubMed  CAS  Google Scholar 

  • Izzo AA (2005) Herb-drug interactions: an overview of the clinical evidence. Fund Clin Pharmacol 76:1–16

    Article  CAS  Google Scholar 

  • Kiewert C, Buchholzer ML, Hartmann J, Chatterjee SS, Klein J (2004) Stimulation of hippocampal acetylcholine release by hyperforin, a constituent of St. John’s wort. Neurosci Lett 364:195–198

    Article  PubMed  CAS  Google Scholar 

  • Knuppel L, Linde K (2004) Adverse effects of St. John’s wort: a systematic review. J Clin Psychiatr 65:1470–1479

    Article  Google Scholar 

  • Koch E, Chatterjee SS (2001) Hyperforin stimulates intracellular calcium mobilisation and enhances extracellular acidification in DDT1-MF2 smooth muscle cells. Pharmacopsychiatry 34:S70–S73

    Article  PubMed  CAS  Google Scholar 

  • Koch KL, Stern RM (1996) Functional disorders of the stomach. Semin Gastrointest Dis 7:185–195

    PubMed  CAS  Google Scholar 

  • Linde K, Berner M, Egger M, Mulrow C (2005) St. John’s wort for depression: meta-analysis of randomised controlled trials. Br J Psychiatr 186:99–107

    Article  Google Scholar 

  • Lipka E, Crison JR, Schug BS, Blume HH, Amidon GL (1996) Drug interaction in the gastrointestinal tract and their impact on drug absorption and systemic availability: a mechanistic review. Hand Exp Pharmacol 122:13–37

    CAS  Google Scholar 

  • Makhlouf GM (1987) Isolated smooth muscle cells of the gut. In: Jonhson LR (ed) Physiology of the gastrointestinal tract. Raven, New York, pp. 555–570

    Google Scholar 

  • Mannel M (2004) Drug interactions with St. John’s wort: mechanisms and clinical implications. Drug Saf 27:773–797

    Article  PubMed  CAS  Google Scholar 

  • Mennini T, Gobbi M (2004) The antidepressant mechanism of Hypericum perforatum. Life Sci 75:1021–1027

    Article  PubMed  CAS  Google Scholar 

  • Nocerino E, Izzo AA, Borrelli F, Capasso F, Capasso R, Pinto L, Sautebin L, Mascolo N (2002) Relaxant effect of capsazepine in the isolated rat ileum. Naunyn-Schmiedebergs Arch Pharmacol 365:187–192

    Article  PubMed  CAS  Google Scholar 

  • Read NW, Houghton LA (1989) Physiology of gastric emptying and pathophysiology of gastroparesis. Gastroenterol Clin North Am 18:359–373

    PubMed  CAS  Google Scholar 

  • Simbrey K, Winterhoff H, Butterweck V (2004) Extracts of St. John’s wort and various constituents affect beta-adrenergic binding in rat frontal cortex. Life Sci 74:1027–1038

    Article  PubMed  CAS  Google Scholar 

  • Szegedi A, Kohnen R, Dienel A, Kieser M (2005) Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St. John’s wort): randomised controlled double blind non-inferiority trial versus paroxetine. BMJ 330:503

    Article  PubMed  CAS  Google Scholar 

  • Tagliamonte A (1999) Efficacy of an Hypericum perforatum (St. John’s wort) extract in preventing and reverting a condition of escape deficit in rats. Neuropsychopharmacology 21:247–257

    Article  PubMed  Google Scholar 

  • Taniyama K, Makimoto N, Furuichi A, Sakurai-Yamashita Y, Nagase Y, Kaibara M, Kanematsu T (2000) Functions of peripheral 5-ydroxytryptamine receptors, especially 5-hydroxytryptamine4 receptor, in gastrointestinal motility. J Gastroenterol 35:575–582

    Article  PubMed  CAS  Google Scholar 

  • Tedeschi E, Menegazzi M, Margotto D, Suzuki H, Forstermann U, Kleinert H (2003) Anti-inflammatory actions of St. John’s wort: inhibition of human inducible nitric-oxide synthase expression by down-regulating signal transducer and activator of transcription-1alpha (STAT-1alpha) activation. J Pharmacol Exp Ther 307:254–261

    Article  PubMed  CAS  Google Scholar 

  • Whitten DL, Myers SP, Hawrelak JA, Wohlmuth H (2006) The effect of St. John’s wort extracts on CYP3A: a systematic review of prospective clinical trials. Br J Clin Pharmacol 62:512–526

    Article  PubMed  CAS  Google Scholar 

  • Williamson EM (2005) Interactions between herbal and conventional medicines. Expert Opin Drug Saf 4:355–378

    Article  PubMed  CAS  Google Scholar 

  • Zhou S, Chan E, Pan SQ, Huang M, Lee EJ (2004) Pharmacokinetic interactions of drugs with St. John’s wort. J Psychopharmacol 18:262–276

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by PRIN, Regione Campania, and “Fondazione Enrico ed Enrica Sovena”.

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Authors and Affiliations

  1. Department of Experimental Pharmacology, University of Naples Federico II, via D Montesano 49, 80131, Naples, Italy

    Raffaele Capasso, Francesca Borrelli, Gabriella Aviello, Francesco Capasso & Angelo A. Izzo

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  1. Raffaele Capasso
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  2. Francesca Borrelli
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  3. Gabriella Aviello
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  4. Francesco Capasso
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  5. Angelo A. Izzo
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Correspondence to Raffaele Capasso or Angelo A. Izzo.

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Capasso, R., Borrelli, F., Aviello, G. et al. Inhibitory effect of the herbal antidepressant St. John’s wort (Hypericum perforatum) on rat gastric motility. Naunyn-Schmied Arch Pharmacol 376, 407–414 (2008). https://doi.org/10.1007/s00210-007-0230-2

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  • DOI: https://doi.org/10.1007/s00210-007-0230-2

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