The bioassay-guided fractionation of protective agents against sepsis-induced lethality from the root cortex of Paeonia suffruticosa ANDREWS (Ranunculaceae) led to the isolation of eight known compounds: paeonol (1), 2,5-dihydroxy-4-methoxyacetophenone (2), acetovanillone (3), paeonoside (4), paeoni...
The bioassay-guided fractionation of protective agents against sepsis-induced lethality from the root cortex of Paeonia suffruticosa ANDREWS (Ranunculaceae) led to the isolation of eight known compounds: paeonol (1), 2,5-dihydroxy-4-methoxyacetophenone (2), acetovanillone (3), paeonoside (4), paeoniflorin (5), oxypaeoniflorin (6), apiopaeonoside (7), and methyl 3-hydroxy-4-methoxybenzoate (8). Among them, 3 showed the highest survival rate (100% with a dose of 30 mg/kg versus 17% for the control experiment) and reduced alanine aminotransferase level to be a half of the control value on the sepsis model induced by lipopolysaccharide/D-galactosamine.
The bioassay-guided fractionation of protective agents against sepsis-induced lethality from the root cortex of Paeonia suffruticosa ANDREWS (Ranunculaceae) led to the isolation of eight known compounds: paeonol (1), 2,5-dihydroxy-4-methoxyacetophenone (2), acetovanillone (3), paeonoside (4), paeoniflorin (5), oxypaeoniflorin (6), apiopaeonoside (7), and methyl 3-hydroxy-4-methoxybenzoate (8). Among them, 3 showed the highest survival rate (100% with a dose of 30 mg/kg versus 17% for the control experiment) and reduced alanine aminotransferase level to be a half of the control value on the sepsis model induced by lipopolysaccharide/D-galactosamine.
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제안 방법
suffruticosa was partitioned with methylene chloride, EtOAc and H2O, successively, which were then dried. When each of those solvent fractions were pretreated to LPS/D-GalN-induced lethality model (500 ㎎/㎏), the group of mice, pretreated with the methylene chloride fraction, showed increased survival rate of 4 out of 5 mice comparing to the control experiment in which all 5 mice were dead after 48 h (Table I). The methylene chloride fraction was further chromatographed on a silica gel column, reverse-phase column and two major column fractions were recrystallized, which afford paeonol (1), 2, 5-dihydroxy-4-rTiethoxyaceto-phenone (2), acetovanillone (3), paeonoside (4), paeoniflorin (5), oxypaedhiflorin (6), apiopaeonoside (7), and methyl3-hydroxy-4-methoxybenzoate (8), respectively.
대상 데이터
The root cortex of P. suffiuticosa was purchased in March 1999 from a folk medicine market, "Yak-ryong-si" in Daegu and the material was confirmed taxonomically by Professor Ki-Hwan Bae, of Chungnam National University in Daejeon, Republic of Korea. A voucher specimen (YNS-99-01) is preserved at the College of Pharmacy, Yeungnam University.
Spots were detected under UV radiation and by spraying with 10% H2SO4, followed by heating. Dexamethasone was purchased from Sigma Chemicals (St. Louis, MO, USA). All other chemicals and solvents were analytical grade and used without further purification.
Five male ICR mice weighing 23-28 g were housed in a cage at a room temperature between 22+1 ℃ with an alternating 12 h light-dark cycle. Food and water were available ad libitum.
데이터처리
Statistical analysis was carried out by one-way analysis of variance (ANOVA). Bonferroni and Newman-Keuls tests were used for post-hoc comparisons.
이론/모형
Liver damage was evaluated by measuring plasma ALT using ALT kit (Yeongdong Pharmaceutical Corp., Seoul, Korea) according to Reitman-Frankel method. Plasma samples were diluted to 1:20 prior to ALT measurement.
성능/효과
In conclusion, acetovanillone (3) from the root cortex of Paeonia suffruticosa was isolated as a major compound which exhibited the protective effect against sepsis induced by LPS/D-GalN in mice and it reduced ALT level in the same sepsis model. Other biochemical mechanistic studies of these compounds are under progress now.
Ⅲ). In order to investigate the effect of 3 on liver damage due to LPS/D-GalN treatment in mice, ALT values were measured, which showed about 50% reduction of ALT activity in plasma samples of mice pretreated with 3 (30 ㎎/㎏) comparing to those of control LPS/D-GalN-treated group (Fig. 1). However, 3 exhibited less protectiv으 activity against sepsis than the positive control, dexamethasone when both survival rates and ALT activities were compared between two.
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