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Protective effects of ginsenoside Rb(3) on oxygen and glucose deprivation-induced ischemic injury in PC12 cells.
Acta Pharmacol Sin. 2010 Mar; 31(3):273-80.AP

Abstract

AIM

To investigate the protective effects of ginsenoside Rb(3), a triterpenoid saponin isolated from the leaves of Panax notoginseng, on ischemic and reperfusion injury model of PC12 cells and elucidate the related mechanisms.

METHODS

PC12 cells exposed to oxygen and glucose deprivation (OGD) and restoration (OGD-Rep) were used as an in vitro model of ischemia and reperfusion. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) leakage were used to evaluate the protective effects of ginsenoside Rb(3). Cellular apoptosis and mitochondrial membrane potential (MMP) were analyzed using flow cytometry. Intracellular calcium ion concentration ([Ca(2+)](i)) was detected using fluorophotometer system. Caspase-3, -8, and -9 activities were measured using assay kits with an ELISA reader. Western blotting assay was used to evaluate the release of cytochrome c and expression of caspase-3, Bcl-2 and Bax proteins.

RESULTS

It was shown that ginsenoside Rb(3) (0.1-10 micromol/L) significantly increased cell viability and inhibited LDH release in a dose-dependent manner on the ischemic model. In addition, ginsenoside Rb(3) also significantly inhibited ischemic injury-induced apoptosis, [Ca(2+)](i) elevation, and decrease of MMP. Meanwhile, pretreatment with ginsenoside Rb(3) significantly induced an increase of Bcl-2 protein expression and a decrease of cytosolic cytochrome c, cleaved-caspase 3 and Bax protein expression, the caspase-3, -8, and -9 activity were also inhibited.

CONCLUSION

The results indicated that ginsenoside Rb(3) could markedly protected OGD-Rep induced ischemic injury and the mechanisms maybe related to its suppression of the intracellular Ca(2+) elevation and inhibition of apoptosis and caspase activity. Ginsenoside Rb(3) could be a promising candidate in the development of a novel class of anti-ischemic agent.

Authors+Show Affiliations

Department of Pharmacy, Nanjing First Hospital Affiliated to Nanjing Medical University, China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20140005

Citation

Zhu, Jun-rong, et al. "Protective Effects of Ginsenoside Rb(3) On Oxygen and Glucose Deprivation-induced Ischemic Injury in PC12 Cells." Acta Pharmacologica Sinica, vol. 31, no. 3, 2010, pp. 273-80.
Zhu JR, Tao YF, Lou S, et al. Protective effects of ginsenoside Rb(3) on oxygen and glucose deprivation-induced ischemic injury in PC12 cells. Acta Pharmacol Sin. 2010;31(3):273-80.
Zhu, J. R., Tao, Y. F., Lou, S., & Wu, Z. M. (2010). Protective effects of ginsenoside Rb(3) on oxygen and glucose deprivation-induced ischemic injury in PC12 cells. Acta Pharmacologica Sinica, 31(3), 273-80. https://doi.org/10.1038/aps.2010.9
Zhu JR, et al. Protective Effects of Ginsenoside Rb(3) On Oxygen and Glucose Deprivation-induced Ischemic Injury in PC12 Cells. Acta Pharmacol Sin. 2010;31(3):273-80. PubMed PMID: 20140005.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effects of ginsenoside Rb(3) on oxygen and glucose deprivation-induced ischemic injury in PC12 cells. AU - Zhu,Jun-rong, AU - Tao,Yi-fu, AU - Lou,Shen, AU - Wu,Zi-mei, Y1 - 2010/02/08/ PY - 2010/2/9/entrez PY - 2010/2/9/pubmed PY - 2010/6/15/medline SP - 273 EP - 80 JF - Acta pharmacologica Sinica JO - Acta Pharmacol. Sin. VL - 31 IS - 3 N2 - AIM: To investigate the protective effects of ginsenoside Rb(3), a triterpenoid saponin isolated from the leaves of Panax notoginseng, on ischemic and reperfusion injury model of PC12 cells and elucidate the related mechanisms. METHODS: PC12 cells exposed to oxygen and glucose deprivation (OGD) and restoration (OGD-Rep) were used as an in vitro model of ischemia and reperfusion. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) leakage were used to evaluate the protective effects of ginsenoside Rb(3). Cellular apoptosis and mitochondrial membrane potential (MMP) were analyzed using flow cytometry. Intracellular calcium ion concentration ([Ca(2+)](i)) was detected using fluorophotometer system. Caspase-3, -8, and -9 activities were measured using assay kits with an ELISA reader. Western blotting assay was used to evaluate the release of cytochrome c and expression of caspase-3, Bcl-2 and Bax proteins. RESULTS: It was shown that ginsenoside Rb(3) (0.1-10 micromol/L) significantly increased cell viability and inhibited LDH release in a dose-dependent manner on the ischemic model. In addition, ginsenoside Rb(3) also significantly inhibited ischemic injury-induced apoptosis, [Ca(2+)](i) elevation, and decrease of MMP. Meanwhile, pretreatment with ginsenoside Rb(3) significantly induced an increase of Bcl-2 protein expression and a decrease of cytosolic cytochrome c, cleaved-caspase 3 and Bax protein expression, the caspase-3, -8, and -9 activity were also inhibited. CONCLUSION: The results indicated that ginsenoside Rb(3) could markedly protected OGD-Rep induced ischemic injury and the mechanisms maybe related to its suppression of the intracellular Ca(2+) elevation and inhibition of apoptosis and caspase activity. Ginsenoside Rb(3) could be a promising candidate in the development of a novel class of anti-ischemic agent. SN - 1745-7254 UR - https://www.unboundmedicine.com/medline/citation/20140005/Protective_effects_of_ginsenoside_Rb_3__on_oxygen_and_glucose_deprivation_induced_ischemic_injury_in_PC12_cells_ L2 - http://dx.doi.org/10.1038/aps.2010.9 DB - PRIME DP - Unbound Medicine ER -