In this study, we systematically investigated the plasma pharmacokinetics, tissue\ndistribution, and elimination of three active alkaloids after oral administration of the effective\nfraction of alkaloids from Ramulus Mori (SZââ?¬â??A)ââ?¬â?an innovative hypoglycemic agentââ?¬â?in rats.\nMoreover, the influences of other components in SZââ?¬â??A on dynamic process of alkaloids were\nexplored for the first time. The results showed that 1-deoxynojirimycin (DNJ), fagomine (FGM)\nand 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) exhibited nonlinear pharmacokinetics following\noral administration of SZââ?¬â??A (40ââ?¬â??1000 mg/kg). The prolonged t1/2 and greater area under\nconcentration-time curve (AUC) versus time (AUC0ââ?¬â??t) of DNJ for SZââ?¬â??A than for purified DNJ has\nbeen observed after both oral and intravenous administration. It was found that other components\nin SZââ?¬â??A could enhance the absorption of DNJ through the intestinal barrier. The major distribution\ntissues of DNJ, FGM, and DAB were the gastrointestinal tract, liver, and kidney. Three alkaloids were\nmainly excreted into urine and feces, but less into bile. Interestingly, the excess excretion of FGM was\nrevealed to be partly due to the biotransformation of other components in SZââ?¬â??A via gut microbiota.\nThese information provide a rational basis for the use of SZââ?¬â??A in clinical practice.
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