ABSTRACT
Byakkokaninjinto (BKN) is an herbal medicine used for the relief of diuresis, thirst and dermal pruritus that are associated with diabetes. The effects of BKN on the expression of aquaporins (AQPs) in the kidney, salivary gland and skin were investigated in order to clarify the mechanism of drug action. Seven-week-old KKAy mice were given feed containing 4.5% BKN for 4 weeks. Compared with the control group, BKN administration did not affect the blood glucose and insulin concentration. However, water intake and urine volume were significantly reduced. AQP2 protein expression in the kidney inner medullary was significantly increased after BKN administration. AQP3 mRNA and protein expression in skin tissue was significantly increased after BKN administration. However, BKN administration did not affect AQP5 mRNA expression in the salivary gland. These results suggest that BKN treatment relieves diuresis, thirst, and dermal pruritis by increasing kidney AQP2 expression and skin AQP3 expression.
Subject(s)
Aquaporin 2/biosynthesis , Aquaporin 3/biosynthesis , Body Water/metabolism , Drugs, Chinese Herbal/pharmacology , Kidney/drug effects , Plant Extracts/pharmacology , Skin/drug effects , Anemarrhena/chemistry , Animals , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Diuresis/drug effects , Gene Expression Regulation/drug effects , Glycyrrhiza/chemistry , Humans , Kidney/metabolism , Mice , Models, Animal , Oryza/chemistry , Panax/chemistry , Salivary Glands/metabolism , Skin/metabolismABSTRACT
Recently, a new compound IT-M-07000 was designed as a prodrug of tamibarotene, one of the therapeutic agents for acute promyelocytic leukemia. In the present study, IT-M-07000 was administered to mice to investigate whether it is actually metabolized to tamibarotene. Its metabolic pathway and the utility as a tamibarotene prodrug were also evaluated. After oral administration of IT-M-07000, IT-M-07000, tamibarotene and two compounds that were supposed to be metabolic intermediates in a beta-oxidation pathway of IT-M-07000 to tamibarotene were detected in mouse plasma. It was thus shown that IT-M-07000 is probably beta-oxidized to tamibarotene in mice. Comparison of tamibarotene concentration profiles after oral administration of IT-M-07000 or tamibarotene showed that the plasma tamibarotene concentration increased slower and was retained stable, and the area under the plasma concentration-time curve (AUC) of tamibarotene was larger in mice administered IT-M-07000 than tamibarotene. These results indicate that IT-M-07000 is possibly useful as a prodrug of tamibarotene.
