Hypoglycemic Effect of the Methanol flower Extract of Piper Claussenianum and the Major Constituent 2',6'-dihydroxy-4'-methoxychalcone in Streptozotocin Diabetic Rats.

Piper claussenianum inflorescences crude methanol extract was tested for hypoglycemic effect in streptozotocin-induced diabetic rats. The blood glucose levels of rats treated with methanol extract were reduced from 318.4±28.1 mg/dl before treatment to 174.2±38.3 mg/dl after 12 days of treatment (P<0.05). Phytochemical studies were carried out on inflorescences methanol crude extract in order to investigate the possible metabolites responsible for the pharmacological properties of the extract. After chromatographic procedures, three flavonoids were isolated and characterized. The major compound 2',6'-dihydroxy-4'-methoxychalcone was also tested. Rats that received the chalcone content also displayed a reduction in blood glucose levels from 277.4±7.7 mg/dl before treatment to 158.8±9.2 mg/dl after 12 days of treatment (P<0.05). The results suggest this chalcone is one of the metabolite responsible for the blood glucose levels reduction in rats with streptozotocin-induced diabetes. The inflorescence crude extract of P. claussenianum was found to be composed mainly by flavonoids and may be a potential natural source of compounds with hypoglycemic properties.

Intracellular [Mg++] determines specificity of K+ channel block by a class III antiarrhythmic drug.

E-4031 and related methanesulfonanilide class III antiarrhythmic drugs block I(Kr), a cardiac delayed rectifier K+ current. The current-voltage relationship of I(Kr) exhibits rectification; currents progressively decline in magnitude at test potentials >0 mV. Whole-cell voltage-clamp techniques were used to determine whether rectification results from block of channels by intracellular Mg++. The properties of E-4031-sensitive current were compared in guinea pig ventricular myocytes internally perfused with either a nominally Mg++ -free solution or with a solution containing 1mM Mg++. Based on an envelope of tails test, we conclude that inward rectification of guinea pig I(Kr) is due to a voltage-dependent gating mechanism and does not result from block of the channel by intracellular Mg++. Under normal physiologic conditions, E-4031 is a specific blocker of I(Kr). However, in the absence of intracellular Mg++, E-4031 also partially blocks I(Ks). Block of I(Ks) is prevented by prior treatment of cells with isoproterenol, which suggests that E-4031 only blocks unphosphorylated I(Ks) channels in the absence of intracellular Mg++.