Description: |
Praeruptorin D exhibits antitumor and anti-inflammatory activities, it protects mice from hydrochloric acid (HCl)-induced lung injury by inhibiting PMNs influx, IL-6 release and protein exudation. Praeruptorin D can significantly up-regulate CYP3A4 expression and activity via the Pregnane X receptor (PXR)-mediated pathway. |
Targets: |
IL Receptor | p65 | NF-kB | TNF-α | P450 (e.g. CYP17) | PXR |
In vitro: |
J Ethnopharmacol. 2013 Jul 9;148(2):596-602. | Up-regulatation of CYP3A expression through pregnent X receptor by praeruptorin D isolated from Peucedanum praeruptorum Dunn.[Pubmed: 23702042 ] | Qianhu, the dried roots of Peucedanum praeruptorum DUNN (Umbelliferae), is a well-known traditional Chinese medicinal herb which was officially listed in the Chinese Pharmacopoeia. Praeruptorin D (PD) is one of the major active constituents of Peucedanum praeruptorum Dunn (Qianhu). The Pregnane X receptor (PXR) is an orphan nuclear receptor and plays a pivotal role in the activation of human cytochrome P450 3A4 (CYP3A4) gene.
The purpose of this study was to investigate the effect of PD on the PXR-mediated transactivation of CYP3A4, and thus to predict potential herb-drug interactions between PD, Qianhu, and the other co-administered drugs that metabolized by CYP3A4.
METHODS AND RESULTS:
The effect of PD on the Cyp3a11, mPXR mRNA expression in mice primary hepatocytes was measured using real-time PCR. The gene expression, protein expression, and catalytic activity of CYP3A4 in the LS174T cells after transfected with PXR expression plasmids were determined by real-time PCR, Western blot analysis, and LC-MS/MS based CYP3A4 substrate assay.
The results revealed that the level of Cyp3a11 gene expression in mice primary hepatocytes was significantly increased by PD, but PD cannot induce the mPXR gene expression. On the other hand, CYP3A4 mRNA, protein expression and functional activity in PXR-over-expression LS174T cells were significantly increased by PD through PXR-mediated pathway; conversely, no significant change was found in the untransfected cells.
CONCLUSIONS:
These findings suggest that PD can significantly up-regulate CYP3A4 expression and activity via the PXR-mediated pathway and this should be taken into consideration to predict any potential herb-drug interactions when PD and Peucedanum praeruptorum Dunn are co-administered with other drugs. |
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In vivo: |
Eur J Pharmacol. 2013 Jun 15;710(1-3):39-48. | Praeruptorin D and E attenuate lipopolysaccharide/hydrochloric acid induced acute lung injury in mice.[Pubmed: 23588118] | Acute lung injury is a life-threatening syndrome characterized by overwhelming lung inflammation and increased microvascular permeability, which causes a high mortality rate worldwide. The dry root of Peucedanum praeruptorum Dunn has been long used to treat respiratory diseases in China.
METHODS AND RESULTS:
In the present study, Praeruptorin A, C, Praeruptorin D and E (PA, PC, PD and PE), four pyranocoumarins extracted from this herb, have been investigated for the pharmacological effects in experimental lung injury mouse models. Praeruptorin D and PE significantly inhibited the infiltration of activated polymorphonuclear leukocytes (PMNs) and decreased the levels of TNF-α and IL-6 in bronchoalveolar lavage fluid at the same dose. There was no statistically significant difference between Praeruptorin D and PE group. Further study demonstrated that Praeruptorin D and PE suppressed protein extravasations in bronchoalveolar lavage fluid, attenuated myeloperoxidase (MPO) activity and the pathological changes in the lung. Both Praeruptorin D and PE suppressed LPS induced Nuclear Factor-kappa B (NF-κB) pathway activation in the lung by decreasing the cytoplasmic loss of Inhibitor κB-α (IκB-α) protein and inhibiting the translocation of p65 from cytoplasm to nucleus.
CONCLUSIONS:
Taken together, these results suggested that Praeruptorin D and PE might be useful in the therapy of lung injury. |
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