Effect of Matricaria recutita L. water extract on human cAMP and cGMP phosphodiesterases

Tea infusion of Matricaria recutita L. flowers is a herbal remedy used for the treatment of gastrointestinal (GI) complaints, including minor spasms, epigastric distension, flatulence and belching [1]. The spasmolytic activity has been shown in vitro and in clinical studies [1]. cAMP and cGMP levels regulate the GI smooth muscle tone causing relaxation. Inhibition of phosphodiesterases (PDEs) which catalyze the hydrolysis of cAMP and cGMP to 5’AMP and 5’ GMP, respectively [2], is one of the mechanisms operated by spasmolytic drugs. In the GI tract, PDE3A isoform is the main cAMP-PDE, whereas PDE5A is the main cGMP-specific PDE [2]. In this study the effect of water extracts of dried capitula and sifted flowers on the activity of cAMP- and cGMP-PDEs was investigated. For this purpose, human recombinant PDE5A1 was prepared by expression of the full-length cDNA of PDE5A1 into COS-7 cells [3] and cAMP-PDE was evaluated in human platelet homogenate. PDE activity was determined according to the method described in [4]. Tea infusions (1g dried drug/60ml water at boiling temperature) were prepared from both capitula and sifted chamomile, and lyophilized. The recovery was 19.8 ± 2.0 and 26.1 ± 2.7 respectively (% vs dried drug, mean ± SD, n=6). Infusions were tested at concentrations of 5-100 µg/ml. The extracts did not affect PDE5A1 while inhibited cAMP-PDE in a concentration-dependent fashion; the IC50 values were 30.8 ± 6.3 µg/ml and 31.4 ± 4.2 µg/ml (mean ± S.D.) for capitula and sifted flowers, respectively. To investigate which component/s could be responsible for the effect, we tested apigenin-7-glucoside, luteolin-7-glucoside, the corresponding aglycons, and α-bisabolol. At 10 µM, only flavone derivatives inhibited cAMP-PDE, while α-bisabolol was inactive. Aglycons showed higher activity than the corresponding glucosides. Apigenin-7-glucoside, the main flavone present in chamomile [1], was tested then on cAMP-PDE in the range 1-100 µM and the IC50 was calculated (10.2 ± 1.7 µM ± S.D.). On the contrary, apigenin-7-glucoside was inactive on PDE5A1, even at 50 μM, the maximal concentration assayed, indicating that this flavone may specifically inhibit different PDE isoforms. In addition, these results suggest that apigenin-7-glucoside is the constituent mainly responsible for this pharmacological effect. Analytical studies are ongoing to identify and quantify the extract components. In conclusion, the inhibition of cAMP-PDE could in part explain the mechanism of the spasmolytic action of chamomile.