| Description: |
Oxypeucedanin is a kind of open-channel blocker of the hKv1.5 channel and it prolongs the APD, it is an excellent candidate as an antiarrhythmic drug for atrial fibrillation.Oxypeucedanin has novel anticancer effect, mediated via induction of G2-M cell cycle arrest and apoptosis in human prostate carcinoma DU145 cells. |
| Targets: |
ERK | p38MAPK | PPAR | hKv1.5 channel | Caspase |
| In vitro: |
| Planta Med. 2011 Sep;77(13):1512-8. | | Effects of oxypeucedanin on global gene expression and MAPK signaling pathway in mouse neuroblastoma Neuro-2A cells.[Pubmed: 21425034] | Oxypeucedanin is a major coumarin aglycone that can be extracted from Ostericum koreanum. Coumarin aglycones have demonstrated various pharmacological effects, including anti-proliferation, anti-inflammation, and anti-pain.
METHODS AND RESULTS:
In this study, in order to understand the pharmacological properties of Oxypeucedanin, we investigated global gene expression alteration in mouse neuroblastoma Neuro-2A cells. Results from the MTT assay indicated no decrease of cell viability up to 100 μM for 24 h. We measured gene expression profiles in Neuro-2A cells treated with either 10 μM or no Oxypeucedanin for 24 h. We selected 128 differentially expressed genes (DEGs) for comparison of gene expression profiles by Bonferroni-adjusted p values (p < 0.1). Analysis of Gene Ontology (GO) biological process terms using the DEGs demonstrated the importance of protein metabolism, particularly ribosomal protein synthesis and protein degradation, intramembrane protein trafficking, and electron transport. Treatment with Oxypeucedanin resulted in the downregulation of most DEGs for ribosomal protein synthesis and the electron transport chain (ETC). In contrast, most DEGs for protein degradation and cellular trafficking systems were upregulated. In addition, we found five upregulated DEGs for core and regulatory proteins involved in the mitogen-activated protein kinase (MAPK) signaling pathway. Independent translational validation of DEGs for MAPK signaling by immunoblot analysis showed consistent agreement with microarray data. Overall protein levels of Erk2 and p38MAPK were elevated, and their phosphorylated forms were also increased.
CONCLUSIONS:
These functional categories, based on transcriptional alteration and complicated modulation of MAPK signaling, might be underlying mechanisms responsible for the various pharmacological effects of Oxypeucedanin. | | Biol Pharm Bull. 2005 Apr;28(4):657-60. | | Effects of oxypeucedanin on hKv1.5 and action potential duration.[Pubmed: 15802805] |
METHODS AND RESULTS:
A furocoumarin derivative, Oxypeucedanin, was purified from Angelica dahurica, and its effects on the human Kv1.5 (hKv1.5) channel and on the cardiac action potential duration (APD), were examined using the patch-clamp technique and the conventional microelectrode technique. Oxypeucedanin inhibited the hKv1.5 current in a concentration-dependent manner, with an IC(50) value of 76 nM, while it had no effect on human eag-related gene (HERG) current. Oxypeucedanin induced an initial fast decline of hKv1.5 current during depolarizations. The inhibition of hKv1.5 channel by Oxypeucedanin was voltage-dependent, especially at depolarizing pulses between -40 and 0 mV which corresponds to the voltage range of the channel's opening. Oxypeucedanin also slowed the deactivation time course, resulting in a tail crossover phenomenon. Additionally, Oxypeucedanin prolonged the APD of rat atrial and ventricular muscles in a dose-dependent manner.
CONCLUSIONS:
These results suggest that Oxypeucedanin is a kind of open-channel blocker of the hKv1.5 channel and it prolongs the APD; therefore, it is an excellent candidate as an antiarrhythmic drug for atrial fibrillation. |
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| In vivo: |
| Pharmacol Rep. 2010 Nov-Dec;62(6):1231-6. | | Anticonvulsant effects of four linear furanocoumarins, bergapten, imperatorin, oxypeucedanin, and xanthotoxin, in the mouse maximal electroshock-induced seizure model: a comparative study.[Pubmed: 21273683] | The aim of this study was to determine and compare the anticonvulsant activities of four natural furanocoumarins [bergapten (5-methoxypsoralen), imperatorin (8-isopentenyloxypsoralen), Oxypeucedanin (5-epoxy-isopentenyloxypsoralen) and xanthotoxin (8-methoxypsoralen)] in the maximal electroshock-induced seizure test in mice.
METHODS AND RESULTS:
The anticonvulsant effects of bergapten, imperatorin, Oxypeucedanin, and xanthotoxin were evaluated at 15, 30, 60 and 120 min after their systemic (intraperitoneal) administration. Tonic hind limb extension (seizure activity) was evoked in adult albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. The time courses of protection by bergapten, imperatorin, Oxypeucedanin and xanthotoxin against maximal electroshock-induced seizures revealed that 300 mg/kg imperatorin and xanthotoxin (C-8 substituted derivatives of psoralen) exerted strong anticonvulsant activity, whereas 300 mg/kg bergapten and Oxypeucedanin (C-5 substituted derivatives of psoralen) did not produce any anticonvulsant activity in this model.
CONCLUSIONS:
In conclusion, imperatorin and xanthotoxin protected the animals against maximal electroshock-induced seizures, whereas bergapten and Oxypeucedanin, despite their chemical and structural similarities to xanthotoxin and imperatorin, exerted no anticonvulsant activity in this seizure test. |
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