Inhibition of human cAMP-phosphodiesterase as a mechanism of the spasmolytic effect of Matricaria recutita L.
Mechanisms underlying the spasmolytic activity of chamomile still remain unclear. Inhibition of cAMP- and cGMP-phosphodiesterases (PDE) is one of the mechanisms operated by spasmolytic drugs. In this study, the effect of chamomile on PDE was investigated. Human platelet cAMP-PDE and recombinant PDE5A1 were assayed in the presence of infusions prepared from sifted flowers and capitula. LC-ESI-MS/MS analysis showed different compositions in infusions made with sifted flowers and capitula. Chamomile inhibited cAMP-PDE activity (IC50 = 17.9-40.5 microg/mL), while cGMP-PDE5 was less affected (-15% at 50 microg/mL). Among the individual compounds tested, only flavonoids showed an inhibitory effect (IC50 = 1.3-14.9 microM), contributing to around 39% of the infusion inhibition; other compounds responsible for cAMP-PDE inhibition still remain unknown. Although experimental evidence supporting the use of chamomile for gastrointestinal minor spasms dates back to the fifties, cAMP-PDE inhibition as a likely mechanism underlying the spasmolytic activity is reported for the first time.
Maschi
Omar
O
Research Centre for the Characterization and Safe Use of Natural Compounds-"Giovanni Galli", Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milano, Italy.
Cero
Esther Dal
ED
Galli
Germana V
GV
Caruso
Donatella
D
Bosisio
Enrica
E
Dell'Agli
Mario
M
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005419:Flavonoids / Q000494:pharmacology; D035264:Flowers / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D031168:Matricaria / Q000737:chemistry / Q000378:metabolism*; D010276:Parasympatholytics / Q000737:chemistry / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D028321:Plant Preparations / Q000737:chemistry / Q000494:pharmacology*
D005419:Flavonoids; D010276:Parasympatholytics; D010726:Phosphodiesterase Inhibitors; D028321:Plant Preparations; D015105:3',5'-Cyclic-AMP Phosphodiesterases