Antispasmodic and bronchodilator activities of St John's wort are putatively mediated through dual inhibition of calcium influx and phosphodiesterase.
The crude extract of aerial parts of St John's wort (Hypericum perforatum) (Hp.Cr) and its fractions were studied in vitro for its possible spasmolytic and bronchodilator activities to rationalize some of its medicinal uses. In rabbit jejunum preparations, Hp.Cr caused a concentration-dependent relaxation of both spontaneous and K+ (80 mm)-induced contractions at a similar concentration range (0.1-1.0 mg/mL), similar to that produced by papaverine, whereas verapamil was relatively potent against K+-induced contractions. Hp.Cr shifted the Ca2+ concentration-response curves (CRCs) to the right, similar to that caused by papaverine or verapamil and also caused leftward shift of isoprenaline-induced inhibitory CRCs, similar to papaverine. In guinea-pig tracheal preparations, Hp.Cr caused relaxation of carbachol and K+-induced contractions at similar concentrations (0.01-0.3 mg/mL) and also shifted the isoprenaline-induced inhibitory CRCs to the left, similar to that caused by papaverine. In rabbit aorta preparations at rest, Hp.Cr produced a moderate vasoconstriction, while exhibited vasodilator effect against phenylephrine and K+-induced contractions. Papaverine and verapamil also produced similar non-specific vasodilation, but were devoid of any vasoconstrictor effect. Hp.Cr caused suppression of atrial force of contractions at concentrations about 20 times higher than those that produced inhibitory effect in smooth muscle preparations, similar to papaverine. These results suggest that the spasmolytic effects of Hp.Cr are mediated through dual inhibition of calcium influx and phosphodiesterase (PDE)-like mechanisms, which might explain the medicinal use of St John's wort in the disorders of gastrointestinal and respiratory tracts. Furthermore, the presence of Ca2+ antagonist and PDE inhibitory-like constituents might also be contributing to some extent in the well established use of plant in depression.
Gilani
Anwarul Hassan
AH
Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi-74800, Pakistan. anwar.gilani@aku.edu
Khan
Arif-ullah
AU
Subhan
Fazal
F
Khan
Munasib
M
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011817:Rabbits
D001993:Bronchodilator Agents; D010276:Parasympatholytics; D010726:Phosphodiesterase Inhibitors; D002118:Calcium