The Effect Of Dragon’s Blood And Its Components On Capsaicin-Induced TRPV1Current

In order to explore the mechanism and the material basis for the pharmacologicaleffect of Dragon’s Blood on transient potential vanilloid receptor1(TRPV1), thewhole-cell patch clamp technique was used to observe the effects of Dragon’s Bloodand the combined effects of its three components (cochinchinenin A, cochinchinenin Band loureirin B) on capsaicin-induced TRPV1currents in acute-isolated dorsal rootganglion (DRG) neurons of rats. In current-clamped DRG neurons, the combined effectof the above-mentioned three components on capsaicin-induced membranedepolarization was also observed. In the absence and presence of the combination ofthe three components, the standardized capsaicin-induced TRPV1currents were usedas a function of the capsaicin concentration to draw the dose-response curve ofcapsaicin. And then the interactions of the combined effects produced by variouscombinations of the three components were evaluated by means of three isobolesequations. Results showed that Dragon’s Blood could inhibit capsaicin-induced TRPV1currents in a dose-dependent way. Furthermore, the combination in which the massratio of cochinchinenin A, cochinchinenin B and loureirin B was in agreement withthat in Dragon’s Blood could produce a similar inhibition on capsaicin-induced TRPV1currents as Dragon’s Blood. Both the three components used alone or in combinationcould inhibit capsaicin-induced TRPV1currents, but the concentrations of the threecomponents used alone were respectively higher than those used in combination whentheir inhibition rates were50%. When we changed the mass ratio of the threecomponents and reduced the total dose of the combination, the new combinationprepared in this way could still inhibit capsaicin-induced TRPV1currents. In addition,the loureirin B membrane depolarization and the new combination could blockcapsaicin-induced action potential bursting in current-clamped DRG neurons and thenew combination decrease the maximum value of capsaicin-induced TRPV1currents.The combined effects of the three components were synergistic. These resultssuggested that the combination in which the mass ratio of the three components was inagreement with that in Dragon’s Blood constituted the material basis for the inhibition of Dragon’s Blood on capsaicin-induced TRPV1currents. The mass ratio of the threecomponents in the combination should be optimized to further reduce the total dose ofthe combination and make it produce higher pharmacological effect. The combinedeffects of the three components on TRPV1in voltage-clamped mode were inagreement with those in current-clamped mode. Just increasing the capsaicinconcentration could not offset the inhibition produced by the combination oncapsaicin-induced TRPV1currents, which indicated that the combination of the threecomponents may antagonize TRPV1in the noncompetitive antagonistic model.