Interaction Between Daidzein and Hesperetin on Antispasmodic Action in Isolated Sensitized and Non-sensitized Guinea-Pig Tracheas

In traditional Chinese medicine (TCM), a combination of kudzu and Chen-Pi is frequently prescribed for relieving colds, fever, bronchitis, and cough. It contains daidzein and hesperetin, selective inhibitors of family 3 (PDE3), and 4 (PDE4) of phosphodiesterases (PDEs), respectively. In passively sensitized human airways, allergen-induced contraction was reported to be inhibited only by the simultaneous inhibition of PDE3 and PDE4, but not by single inhibition of either isozyme. Therefore, we are interested in investigating the interaction between daidzein and hesperetin on their antispasmodic effects in the isolated sensitized and non-sensitized guinea-pig tracheas, to clarify the difference between these two tissues, because effects of TCM prescription on patients with or without allergic asthma are often different. Guinea-pigs were sensitized by subcutaneous injection of ovalbumin (OVA) into legs. After sensitization, the baseline and cumulative OVA-induced contractions of the sensitized trachea were isometrically recorded on a polygraph. In the same way, the histamine (30 μM)-induced tonic contraction of non-sensitized guinea-pig trachea was recorded. The isobole method was used to analyze the antagonism and synergism between daidzein and hesperetin. The isoboles showed antagonism between daidzein and hesperetin on baseline relaxant effect and OVA (100 μg/ml)-induced contraction in the sensitized guinea-pig trachea. In contrast, the isobole showed synergism between daidzein and hesperetin on the relaxant effect of histamine-induced tonic contraction in non-sensitized guinea-pig trachea. These results suggest that the combination of kudzu and Chen-Pi for relieving colds, fever, bronchitis and cough is effective in patients without, but might show little effect in patients with allergic asthma.