Table 1.
Major ingredients and their biological activities associated with ghrelin enhancer activity in rikkunshito.
Fig 1.
Flow diagram of participants through the randomized study
Table 2.
Clinical and demographic characteristics of study participants.
BMI; body mass index. Data represent the median (minimum–maximum).
Table 3.
Quantification of rikkunshito ingredients in plasma.
BQL; below the quantification limit. Plasma concentration of [6]-gingerol, [8]-gingerol, [10]-gingerol, [6]-shogaol, [8]-shogaol, ginsenoside Rb2, ginsenoside Re, ginsenoside Rf, ginsenoside Rg1, ginsenoside Rg2, hesperidin, hesperetin, narirutin, and PTH-15 were BQL at all time points. Each value represents mean ± standard deviation (S.D.) (n = 4).
Table 4.
Quantification of rikkunshito ingredients in enzyme-treated plasma.
BQL; below the quantification limit. Each value represents mean ± S.D. (n = 4).
Fig 2.
Chemical structures of nine ingredients derived from rikkunshito
Fig 3.
Plasma concentrations of nine ingredients derived from rikkunshito A; atractylodin, B; atractylodin carboxylic acid, C; pachymic acid, D; heptamethoxyflavone, E; naringenin, F; nobiletin, G; liquiritigenin, H; isoliquiritigenin, I; 18β-glycyrrhetinic acid.
Blood samples were collected at 0 (beginning of the study), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 h after administration of rikkunshito (2.5, 5.0, or 7.5 g/day). Each value represents mean ± S.D. (n = 19–21).
Table 5.
Pharmacokinetic parameters of rikkunshito ingredients.
-: t1/2 was not calculated for all subjects.
Table 6.
Quantification of rikkunshito ingredients in urine.
BQL; below the quantification limit. Amount of ingredients of [10]-gingerol, ginsenoside Rb1, ginsenoside Rc, ginsenoside Rd, ginsenoside Rg2, pachymic acid, nobiletin, tangeretin, heptamethoxyflavone, PTH-15, and oleanolic acid in urine were BQL at all time points. Each value represents mean ± S.D. (n = 4).
Table 7.
Quantification of rikkunshito ingredients in enzyme-treated urine.
BQL; below the quantification limit. Because a calibration curve could not be constructed, owing to a matrix effect (urine treated with β-glucuronidase), naringenin was not analyzed. Each value represents mean ± S.D. (n = 4).
Fig 4.
Relations between dosage and Cmax or AUC0–last A; atractylodin, B; 18β-glycyrrhetinic acid, C, D; atractylodin carboxylic acid.
A power regression model was fitted to a mixed-effect model for evaluation of linearity. CI; confidence interval.