Comparative Study on the ACTH-Releasing Activities of Berberine,Palmatine and Tetrahydropalmatine (Corydalis B) in the Rat

Corydalis B has been reported to have a stimulatory action on the release of ACTH in rats. Since the structural formulae of berberine and palmatine closely resemble that of corydalis B, an attempt was made to compare the effect of these three compounds on the secretion of ACTH by the pituitary. The depletion of adrenal ascorbic acid of rats was used as the criterion for the secretion of ACTH. For comparison, some of the results described in the previous paper are also included here. Subcutaneous injection of corydalis B (25,50mg kg), berberine (5,10mg/kg)or palmatine (25, 50 mg/kg) depleted significantly the adrenal ascorbic acid content of the rat. The action of these three compounds was abolished by hypophysectomy. Pretreatment of rats with pentobarbital (40 mg/kg) almost completely inhibited the adrenal ascorbic acid depleting action of corydalis B and of berberine, but not that of palmatine. However, the depletion of adrenal ascorbic acid by palmatine was inhibited completely by prior injection of morphine (20mg/kg) in rats under pentobarbital anesthesia. After six consecutive daily injections of corydalis B (70 mg/kg/daily) the rats developed tolerance (or adaptation) to the stimulatory action of the compound on the pituitary gland, while berberine and palmatine lacked this property. In addition, corydalis B, injected repeatedly at the daily dosage of 70 mg/kg for 6 consecutive days, could inhibit the release of ACTH activated by cold stress (8℃ or 4℃ for 1 hour) in rats. The above results indicate that the effects of corydalis B, berberine and palmatine on the pituitary-adrenal system are similar in certain aspects, but different in each others. This is presumably due to the differences in the molecular structure paticularly the third ring of the compounds.