Praeruptorin C

Toxicol In Vitro. 2013 Mar;27(2):908-14.

The neuroprotective effect of praeruptorin C against NMDA-induced apoptosis through down-regulating of GluN2B-containing NMDA receptors.[Pubmed: 23313464]

Praeruptorin C (Pra-C), one of the principal bioactive components derived from the root of Peucedanum praeruptorum Dunn, has been widely used as an antioxidant and a calcium antagonist to treat diseases. The present study investigated the protective effect of Pra-C on cultured cortical neuron injury induced by glutamate.
METHODS AND RESULTS:
After challenge with 200μM N-methyl-d-aspartate (NMDA) for 30min, loss of cell viability and excessive apoptotic cell death were observed in cultured cortical neurons. Pra-C conferred protective effects against loss of cellular viability in a concentration-dependent manner. Pra-C also significantly inhibited neuronal apoptosis induced by NMDA exposure by reversing intracellular Ca(2+) overload and balancing Bcl-2 and Bax expression. Furthermore, Pra-C significantly reversed the upregulation of GluN2B-containing NMDA receptors by exposure to NMDA but did not affect the expression of GluN2A-containing NMDA receptors.
CONCLUSIONS:
These findings suggest that Pra-C partially protects cortical neurons by inhibiting the expression of GluN2B-containing NMDA receptors and regulating the Bcl-2 family.

Acta Pharmacol Sin. 2002 Feb;23(2):129-32.

Inhibitory effects of praeruptorin C on cattle aortic smooth muscle cell proliferation.[Pubmed: 11866872]

To study the effects of Praeruptorin C (pra-C) on proliferation of cattle aortic smooth muscle cells (SMC).
METHODS AND RESULTS:
The DNA synthesis of SMC was measured using the incorporation of [3H]thymidine([3H]TdR). Cell cycle phase was evaluated by flow cytometry and cytotoxicity was evaluated by measuring lactic dehydrogenase (LDH) activity. Whether or not treated with angiotensin II (Ang-II), SMC proliferation was suppressed by pra-C in a concentration-dependent manner at range from 0.001 micromol/L to 10 micromol/L. The inhibitory effects appeared to be related to G1-S block in cell cycle traverse while the LDH activities did not change dramatically.
CONCLUSIONS:
Pra-C can completely inhibit SMC proliferation induced by Ang II and partly inhibit the growth of SMC- induced by bovine serum, which is important in prevention and treatment of vascular hyperplastic disease.

Chinese Heart Journal, 2008(5):513-6.

Effects of praeruptorin C on myocardial plasma membrane calcium handling proteins during ischemia/reperfusion[Reference: WebLink]

To explore the cardioprotective mechanism of Praeruptorin C(Pra-C)during ischemia/reperfusion.METHODS Cultured rat neonatal cardiomyocytes were randomly divided into 3 groups: ischemia/reperfusion group(9 h ischemia followed by 1 h reperfusion,I/R),Pra-C pretreatment group(pretreated with Pra-C for 1 h before I/R) and control group.The leakage of intracellular lactate dehydrogenase(LDH) in various groups was determined by biochemical autoanalyzer.Activity of natrium-calcium exchanger(NCX) was indicated by Na+-dependent 45Ca2+ uptake tested by liquid scintillation counting.Semi-quantitative RT-PCR was employed to detect the mRNA level of NCX.Activity of plasma membrane calcium ATPase(PMCA) was determined by microcolorimetrg of inorganic phosphorus. Compared with that in I/R group,the LDH leakage in Pra-C pretreatment group was significantly reduced(P0.01).The Na+-dependent 45Ca2+ uptake was significantly increased in I/R group(P0.01) compared with that in control group.This increase could be significantly attenuated in Pra-C pretreatment group.The level of NCX mRNA in I/R group was also significantly increased(P0.01) compared with that in control group and this increase could be significantly attenuated in Pra-C pretreatment group(P0.01).No significant change of PMCA activity was observed between various groups.
CONCLUSIONS:
NCX mediates the cardioprotective effect of Pra-C during ischemia/reperfusion in the neonatal rat cardiomyocytes I/R model.

Phytomedicine. 2014 Feb 15;21(3):195-8.

Effects of praeruptorin C on blood pressure and expression of phospholamban in spontaneously hypertensive rats.[Pubmed: 24075213]

The traditional Chinese medicine Praeruptorin C (Pra-c) has many physiological and pharmacological effects, including antagonistic effects on blood pressure and calcium levels, maintenance of cellular calcium homeostasis, and improved cardiac systolic and diastolic function. It is potentially a novel and versatile drug for the treatment and prevention of cardiovascular diseases. To explore the possible impact of Praeruptorin C on blood pressure in SHR and its mechanism of action.
METHODS AND RESULTS:
SHR treated with Praeruptorin C for 8 weeks had a lower systolic pressure than untreated SHR (p<0.05), two measures of cardiac damage, the heart mass index and left ventricle mass index (HMI and LVMI, respectively) were improved, and the level of PLB mRNA expression was lower in the untreated SHR group (p<0.05).
CONCLUSIONS:
With continuous hypertension, SHR gradually formed or developed cardiac hypertrophy and fibrosis. Praeruptorin C had a clear effect on blood pressure in SHR, and reversed SHR ventricular remodeling by upregulating the gene expression of sarcoplasmic reticulum PLB.

Yao Xue Xue Bao. 1993;28(10):728-31.

Effects of praeruptorin-C on cytosolic free calcium in cultured rat heart cells[Pubmed: 7516604]

The negative inotropic effect of Praeruptorin C(Pra-C) was supposed to be related to the blocking of extracellular calcium influx but direct evidence is not known.
METHODS AND RESULTS:
We, therefore, examined the effects of Pra-C on [Ca2+]i in isolated rat ventricular myocytes using the fluorescent Ca(2+)-indicator Fura-2/AM. It was found that Pra-C inhibited the elevation of [Ca2+]i induced by potassium-depolarization, high extracellular calcium and calcium agonist Bay K 8644 in a dose-dependent manner. At 1.0 mumol.L-1, it decreased the [Ca2+]i at the presence of 75 mmol.L-1 KCl, 10 mol.L-1 CaCl and 3 mumol.L-1 Bay K 8644 by 50, 31 and 42% respectively. No significant effect on ouabain evoked [Ca2+]i increase was found, showing that it does not affect sarcolemmal Na(+)-Ca2+ exchange.
CONCLUSIONS:
These results further indicate that Pra-C may decrease the [Ca2+]i of myocyte by blocking voltage-dependent calcium channels.

Evid Based Complement Alternat Med. 2013;2013:156574.

PXR-Mediated Upregulation of CYP3A Expression by Herb Compound Praeruptorin C from Peucedanum praeruptorum Dunn.[Pubmed: 24379885]

We recently reported that Praeruptorin C effectively transactivated the mRNA, protein expression, and catalytic activity of CYP3A4 via the CAR-mediated pathway, but whether and how PC could affect the expression and catalytic activity of CYP3A4 via PXR pathway remains unknown.
METHODS AND RESULTS:
Therefore, in this study, the effect of PC on the CYP3A gene expression was investigated in mice primary hepatocytes after knockdown of PXR by transient transfection of PXR siRNA, and the gene expression, protein expression, and catalytic activity of CYP3A4 in the LS174T cells with PXR overexpression were determined by real-time PCR, western blot analysis, and LC-MS/MS-based CYP3A4 substrate assay, respectively. We found that the level of CYP3a11 gene expression in mouse primary hepatocytes was significantly increased by Praeruptorin C, but such an induction was suppressed after knockdown of pregnane X receptor by its siRNA. In PXR-overexpressed LS174T cells, PC significantly enhanced CYP3A4 mRNA, protein expression, and functional activity through PXR-mediated pathway; conversely, no such increase was found in the untransfected cells.
CONCLUSIONS:
These findings suggest that PC can significantly upregulate CYP3A level via the PXR-mediated pathway, and this should be taken into consideration to predict any potential herb-drug interactions between PC, Qianhu, and the other coadministered drugs.