| Description: |
Praeruptorin B has significant important phase II drug-metabolizing enzymes uridine 5'-diphospho-glucuronosyltransferase (UGTs) isoforms inhibition activity. Praeruptorin B and praeruptorin A have LC 50 values of 34.5 and121.2 ug/ml, respectively, in Artemia salina test . |
| Targets: |
Antifection | UGT |
| In vitro: |
| Phytother Res. 2016 Nov;30(11):1872-1878. | | The Inhibition of UDP-Glucuronosyltransferase (UGT) Isoforms by Praeruptorin A and B.[Pubmed: 27534594 ] | Praeruptorin A (PA) and praeruptorin B (PB) are two important compounds isolated from Bai-hua Qian-hu and have been reported to exert multiple biochemical and pharmacological activities. The present study aims to determine the inhibition of PA and PB on the activity of important phase II drug-metabolizing enzymes uridine 5'-diphospho-glucuronosyltransferase (UGTs) isoforms.
METHODS AND RESULTS:
In vitro UGT incubation system was used to determine the inhibition potential of PA and PB on the activity of various UGT isoforms. In silico docking was performed to explain the inhibition difference between PA and PB towards the activity of UGT1A6. Inhibition behaviour was determined, and in vitro-in vivo extrapolation was performed by using the combination of in vitro inhibition kinetic parameter (Ki ) and in vivo exposure level of PA. Praeruptorin A (100 μM) exhibited the strongest inhibition on the activity of UGT1A6 and UGT2B7, with 97.8% and 90.1% activity inhibited by 100 μM of PA, respectively. In silico docking study indicates the significant contribution of hydrogen bond interaction towards the stronger inhibition of PA than PB towards UGT1A6. Praeruptorin A noncompetitively inhibited the activity of UGT1A6 and competitively inhibited the activity of UGT2B7. The inhibition kinetic parameter (Ki ) of PA towards UGT1A6 and UGT2B7 was calculated to be 1.2 and 3.3 μM, respectively. The [I]/Ki value was calculated to be 15.8 and 5.8 for the inhibition of PA on UGT1A6 and UGT2B7, indicating high inhibition potential of PA towards these two UGT isoforms in vivo.
CONCLUSIONS:
Therefore, closely monitoring the interaction between PA and drugs mainly undergoing UGT1A6 or UGT2B7-catalyzed metabolism is very necessary. | | Phytother Res . 2016 Nov;30(11):1872-1878. | | The Inhibition of UDP-Glucuronosyltransferase (UGT) Isoforms by Praeruptorin A and B[Pubmed: 27534594] | | Abstract
Praeruptorin A (PA) and B (PB) are two important compounds isolated from Bai-hua Qian-hu and have been reported to exert multiple biochemical and pharmacological activities. The present study aims to determine the inhibition of PA and PB on the activity of important phase II drug-metabolizing enzymes uridine 5'-diphospho-glucuronosyltransferase (UGTs) isoforms. In vitro UGT incubation system was used to determine the inhibition potential of PA and PB on the activity of various UGT isoforms. In silico docking was performed to explain the inhibition difference between PA and PB towards the activity of UGT1A6. Inhibition behaviour was determined, and in vitro-in vivo extrapolation was performed by using the combination of in vitro inhibition kinetic parameter (Ki ) and in vivo exposure level of PA. Praeruptorin A (100 μM) exhibited the strongest inhibition on the activity of UGT1A6 and UGT2B7, with 97.8% and 90.1% activity inhibited by 100 μM of PA, respectively. In silico docking study indicates the significant contribution of hydrogen bond interaction towards the stronger inhibition of PA than PB towards UGT1A6. Praeruptorin A noncompetitively inhibited the activity of UGT1A6 and competitively inhibited the activity of UGT2B7. The inhibition kinetic parameter (Ki ) of PA towards UGT1A6 and UGT2B7 was calculated to be 1.2 and 3.3 μM, respectively. The [I]/Ki value was calculated to be 15.8 and 5.8 for the inhibition of PA on UGT1A6 and UGT2B7, indicating high inhibition potential of PA towards these two UGT isoforms in vivo. Therefore, closely monitoring the interaction between PA and drugs mainly undergoing UGT1A6 or UGT2B7-catalyzed metabolism is very necessary. Copyright © 2016 John Wiley & Sons, Ltd.
Keywords: Praeruptorin A; Praeruptorin B; UDP-glucuronosyltransferases (UGTs); drug-drug interaction (DDI). |
|
| In vivo: |
| Farmaco. 2001 May-Jul;56(5-7):417-20. | | Isolation of praeruptorins A and B from Peucedanum praeruptorum Dunn. and their general pharmacological evaluation in comparison with extracts of the drug.[Pubmed: 11482769] | The root of Peucedanum praeruptorum Dunn. was extracted with solvents at different polarity obtaining three chemical fractions: aqueous (H2O), n-butanol (BuOH) and ethyl acetate (AcOEt).
METHODS AND RESULTS:
From AcOEt praeruptorin A and praeruptorin B were isolated by column chromatography on silica gel, using toluene/ethyl acetate as eluent, and identified by 1H and 13C NMR analysis. The extracts and the praeruptorins were tested for gross behavioural effects and acute toxicity in mice; the cytotoxicity on Artemia salina Leach and the antimicrobial activity were also evaluated. None of the tested substances evoked behavioural effects or acute toxicity after oral administration in mice; delayed mortality was observed with AcOEt and praeruptorin A only after intraperitoneal administration of high doses (1 g/kg). In Artemia salina test AcOEt, and praeruptorins
A and praeruptorin B had LC50 values of 40.2, 121.2 and 34.5 microg/ml, respectively.
CONCLUSIONS:
AcOEt and praeruptorin A showed antimicrobial activity on Streptococcus agalactiae; their MIC values were 250 and 100 microg/ml, respectively. |
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