Back
 ABC  Vol.6 No.1 , February 2016
Different Concentrations of Notoginsenoside Rg1 Attenuate Hypoxic and Hypercapnia Pulmonary Hypertension by Reducing the Expression of ERK in Rat PASMCs
Abstract: Pulmonary arterial hypertension (PAH) is a serious disease which is characterized by increased vascular resistance and pressure. We have previously hypothesized that panax notoginseng saponins (PNS) might attenuate pulmonary vasoconstriction under hypoxia and hypercapnia condition. This study aims to investigate the effect of notoginsenoside Rg1, a main ingredient of PNS, with various concentrations (8, 40, 100 mg/L, respectively) on extracellular signal regulated kinase (ERK1/2) signaling pathway in pulmonary arterial smooth muscle cells (PASMCs). In addition, PASMCs were randomly divided into six groups: SD rat under normoxic condition as control group (N group), hypoxia hypercapnia group (H group), DMSO control group (HD group), Rg1-treatment groups (RgLRgM and RgH group). Western-blot and RT-PCR were used to test the expression of p-ERK protein and the expression of ERK1 mRNA and ERK2 mRNA. This study provided the evidence that the expression of p-ERK protein and the expression of ERK1 mRNA and ERK2 mRNA in HD group and H group were obviously higher than that in N group (P < 0.01), Whereas the level of ERK1/2 mRNA in Rg1-treatment groups was significantly lower than that in HD group and H group (P < 0.01), and the proper concentration of Rg1 is 40 mg/L. These results suggested that notoginsenoside Rg1 can attenuate pulmonary vasoconstriction which may lead to HHPV through reducing the expression of ERK1/2.
Cite this paper: Zhang, C. , Ye, L. , Jin, H. , Zhao, M. , Zheng, M. , Song, L. and Wang, W. (2016) Different Concentrations of Notoginsenoside Rg1 Attenuate Hypoxic and Hypercapnia Pulmonary Hypertension by Reducing the Expression of ERK in Rat PASMCs. Advances in Biological Chemistry, 6, 12-18. doi: 10.4236/abc.2016.61002.
References

[1]   Sommer, N., Dietrich, A., Schermuly, R.T., Ghofrani, H.A., et al. (2008) Regulation of Hypoxic Pulmonary Vasoconstriction: Basic Mechanisms. European Respiratory Journal, 32, 1386-1398.
http://dx.doi.org/10.1183/09031936.00013908

[2]   Stenmark, K.R., Fagan, K.A. and Frid, M.G. (2006) Hypoxia-Induced Pulmonary Vascular Remodeling: Cellular and Molecular Mechanisms. Circulation Research, 99, 675-691.
http://dx.doi.org/10.1161/01.RES.0000243584.45145.3f

[3]   Ward, J.P. and McMurtry, I.F. (2009) Mechanisms of Hypoxic Pulmonary Vasoconstriction and Old Problem. Current Opinion in Pharmacology, 9, 287-296.
http://dx.doi.org/10.1016/j.coph.2009.02.006

[4]   Morrell, N.W., Adnot, S., Archer, S.L., et al. (2009) Cellular and Molecular Basis of Pulmonary Arterial Hypertension. Journal of the American College of Cardiology, 54, S20-S31.
http://dx.doi.org/10.1016/j.jacc.2009.04.018

[5]   Ding, L.L., Chapman, A., Boyd, R. and Wang, H.D. (2007) ERK Activation Contributes to Regulation of Spontaneous Contractile Tone via Superoxide Anion in Isolated Rat Aorta of Angiotensin II-Induced Hypertension. American Journal of Physiology—Heart and Circulatory Physiology, 292, H2997-H3005.
http://dx.doi.org/10.1152/ajpheart.00388.2006

[6]   Meloche, S. and Pouysségur, J. (2007) TheERK1/2 Mitogen-Activated Protein Kinase Pathway as a Master Regulator of the G1- to S-Phase Transition. Oncogene, 26, 3227-3239.
http://dx.doi.org/10.1038/sj.onc.1210414

[7]   Li, M., Liu, Y.L., Dutt, P., Fanburg, B.L. and Toksoz, D. (2007) Inhibition of Serotonin-Induced Mitogenesis, Migration, and ERKMAPK Nuclear Translocation in Vascular Smooth Muscle Cells by Atorvastatin. American Journal of Physiology—Lung Cellular and Molecular Physiology, 293, L463-L471.
http://dx.doi.org/10.1152/ajplung.00133.2007

[8]   Yao, Y., Wu, W.Y., Liu, A.H., Deng, S.S., Bi, K.S., Liu, X. and Guo, D.A. (2008) Interaction of Salvianolic Acid and Notoginsengnosides in Inhibition of ADP-Induced Platelet Aggregation. American Journal of Chinese Medicine, 36, 313-328.
http://dx.doi.org/10.1142/S0192415X08005795

[9]   Sun, H.X., Pan, H.J. and Pan, Y.J. (2003) Haemolytic Activity and Immunological Adjuvant Effect of Panaxnotoginsengsaponins. Acta Pharmaceutica Sinica, 24, 1150-1154.

[10]   Chen, S.W., Li, X.H., Ye, K.H., Jiang, Z.F. and Ren, X.D. (2004) Total Saponins of Panaxnotoginseng Protect Rabbit Iliac Artery against Balloon Endothelial Denudation Injury. Acta Pharmaceutica Sinica, 25, 1151-1156.

[11]   Wang, C.Z., McEntee, E., Wicks, S., Wu, J.A. and Yuan, C.S. (2006) Phytochemical and Analytical Studies of Panax notoginseng (Burk.). Journal of Natural Medicines, 60, 97-106.
http://dx.doi.org/10.1007/s11418-005-0027-x

[12]   Liu, Y., Hua, Q., Lei, H. and Li, P. (2011) Effect of Tong Luo Jiu Nao on Aβ-Degrading Enzymes in AD Rat Brains. Journal of Ethnopharmacology, 137, 1035-1046.
http://dx.doi.org/10.1016/j.jep.2011.07.031

[13]   Ma, W.P., Yang, Y.N., Zhou, D.B. and Zhou, W.Q. (2004) The Preventive Effect of Panax notoginseng saponins (PNS) on Chronic Hypoxic Pulmonary Hypertension in Rats. Chinese Journal of Pathophysiology, 20, 1074-1077.

[14]   Li, C.-Y., Deng, W., Liao, X.-Q., Deng, J., Zhang, Y.-K. and Wang, D.-X. (2013) The Effects and Mechanism of Ginsenoside Rg1 on Myocardial Remodeling in an Animal Model of Chronic Thromboembolic Pulmonary Hypertension. European Journal of Medical Research, 18, 16.
http://dx.doi.org/10.1186/2047-783X-18-16

[15]   Zhu, A.A., Wang, W.T. and Lin, L.N. (2008) Effect of Panax notoginseng saponins on the Hypoxia and Hypercapnia Induced Pulmonary Vasoconstriction. Journal of Wenzhou Medical College, 38.

[16]   Yang, X., Sheares, K.K., Davie, N., et al. (2002) Hypoxic Induction of Cox-2 Regulates Proliferation of Human Pulmonary Artery Smooth Muscle Cells. American Journal of Respiratory Cell and Molecular Biology, 27, 688-696.
http://dx.doi.org/10.1165/rcmb.2002-0067OC

[17]   Xu, Y.X., Lin, L.N., Tang, L.L., Zheng, M.X., Ma, Y.C., Huang, L.J., Meng, W. and Wang, W.T. (2014) Notoginsenoside R1 Attenuates Hypoxia and Hypercapnia-Induced Vasocontriction in Isolated Rat Pulmonary Arterial Rings by Reducing the Expression of ERK. The American Journal of Chinese Medicine, 42, 799-816.
http://dx.doi.org/10.1142/S0192415X14500517

[18]   Han, W., Tang, X., Wu, H., Liu, Y. and Zhu, D. (2007) Role of ERK1/2 Signaling Pathways in 4-Amino-Pyridine-Induced Rat Pulmonary Vasoconstriction. European Journal of Pharmacology, 569, 138-144.
http://dx.doi.org/10.1016/j.ejphar.2007.04.042

[19]   Sommer, N., Die-trich, A., Schermuly, R.T., et al. (2008) Regulation of Hypoxic Pulmonary Vasoconstriction: Basic Mechanism. European Respiratory Journal, 32, 1639-1651.

[20]   Li, M., Liu, Y., Dutt, P., et al. (2007) Inhibition of Serotonin-Induced Mitogenesis, Migraiton, and ERKMAPK Nuclear Translocation in Vascular Smooth Muscle Cells by Atorvastatin. American Journal of Physiology—Lung Cellular and Molecular Physiology, 293, L463-L471.
http://dx.doi.org/10.1152/ajplung.00133.2007

[21]   Xia, S., Tai, X., Wang, Y., et al. (2011) Involvement of Gax Gene in Hypoxia-Induced Pulmonary Hypertension, Proliferation, and Apoptosis of Arterial Smooth Muscle Cells. American Journal of Respiratory Cell and Molecular Biology, 44, 66-73.
http://dx.doi.org/10.1165/rcmb.2008-0442OC

[22]   Sztrymf, B., Souza, R., Bertoletti, L., et al. (2010) Prognostic Factors of Acute Heart Failure in Patients with Pulmonary Arterial Hypertension. European Respiratory Journal, 35, 1286-1293.
http://dx.doi.org/10.1183/09031936.00070209

[23]   Welch, L.C., Lecuona, E., Briva, A., Trejo, H.E., Dada, L.A. and Sznajdera, J.I. (2010) Extracellular Signal-Regulated Kinase (ERK) Participates in the Hypercapnia-Induced Na,K-ATPase Down-Regulation. FEBS Letters, 584, 3985-3989.
http://dx.doi.org/10.1016/j.febslet.2010.08.002

[24]   Zhu, A., Lin, N., Wang, W.T., Wang, S.H.J., Jin, K.K., Jin, L.D., Wang, Y. and Wang, Q. (2008) Effect of Panax notoginoside on the Hypoxic Hypercapnia Pulmonary Vasoconstriction. Journal of Wenzhou Medical College, 38, 29-32.

 
 
Top