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Anti-apoptotic Effect of Taxodione on Serum/Glucose Deprivation-Induced PC12 Cells Death

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Abstract

Taxodione, a diterpenoid from the roots of Salvia chorassanica Bunge, possesses cytotoxic, apoptotic, and antimicrobial activity. This study was designed to investigate the protective effects of taxodione on serum/glucose deprivation-induced ischemic injury in PC12 cells and related mechanisms. In an in vitro model of ischemia, PC12 cells were exposed to serum and glucose deprivation for 6 and 18 h. The protective effects of the methanol extract of S. chorassanica and taxodione were assessed using alamarBlue® assay. Intracellular ROS production was measured by fluorimetry using 2′,7′-dichlorofluorescin diacetate (DCFH-DA). The levels of PARP, Bcl-2, and Bax proteins were detected after western blot analysis. It was shown that taxodione (0.2–1.5 μM) significantly increased cell viability in a dose-dependent manner after ischemic insult. Taxodione has antioxidant activity and protects PC12 cells against oxidative stress-induced apoptotic cell death. Meanwhile, pretreatment with taxodione significantly induced an increase in Bcl-2 and a decrease in Bax protein level. The results of this study confirmed the protective effect of taxodione in serum/glucose deprivation-induced ischemic injury and the putative role of apoptosis as a underling mechanisms. Thus, it would be fair to consider taxodione as a promising ingredient of S. chorassanica for the expansion on novel class of anti-ischemic agents.

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References

  • Afsharzadeh M, Tayarani-Najaran Z, Zare A, Mousavi SH (2012) Protective effect of Scutellaria litwinowii extract on serum/glucose-deprived cultured PC12 cells and determining the role of reactive oxygen species. J Toxicol 2012:413279

    PubMed  PubMed Central  Google Scholar 

  • Bao Y, Wang L, Xu Y, Yang Y, Wang L, Si S, Cho S, Hong B (2012) Salvianolic acid B inhibits macrophage uptake of modified low density lipoprotein (mLDL) in a scavenger receptor CD36-dependent manner. Atherosclerosis 223:152–159

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Du G, Zhang J (1997) Protective effects of salvianolic acid A against impairment of memory induced by cerebral ischemia-reperfusion in mice. Chin Med J (Engl) 110:65–68

    CAS  Google Scholar 

  • Dugan LL, Kim-Han JS (2004) Astrocyte mitochondria in in vitro models of ischemia. J Bioenerg Biomembr 36:317–321

    Article  PubMed  CAS  Google Scholar 

  • Ekshyyan O, Aw TY (2004) Apoptosis in acute and chronic neurological disorders. Front Biosci 9:1567–1576

    Article  PubMed  CAS  Google Scholar 

  • Emami SA, Aghazari F (2011) Les Phanerogames Endemiques de la Flore d’Iran. Publications de I’Université de Téhéran, Téhéran, pp 394–395

    Google Scholar 

  • Fisher M (2001) Stroke theraapy, 2nd edn. Butter worth-Heinemann, Woburn, pp 25–50

    Google Scholar 

  • Fraga BM, Díaz CE, Guadaño A, González-Coloma A (2005) Diterpenes from Salvia broussonetii transformed roots and their insecticidal activity. J Agric Food Chem 53:5200–5206

    Article  PubMed  CAS  Google Scholar 

  • Gilgun-Sherki Y, Rosenbaum Z, Melamed E, Offen D (2002) Antioxidant therapy in acute central nervous system injury: current state. Pharm Rev 54:271–284

    Article  PubMed  CAS  Google Scholar 

  • Greene LA, Tischler AS (1976) Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci USA 73:2424–2428

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hillion JA, Takahashi K, Maric D, Ruetzler C, Barker JL, Hallenbeck JM (2005) Development of an ischemic tolerance model in a PC12 cell line. J Cereb Blood Flow Metab 25:154–162

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Johnson EM Jr, Greenlund LJ, Akins PT, Hsu CY (1995) Neuronal apoptosis: current understanding of molecular mechanisms and potential role in ischemic brain injury. J Neurotrauma 12:843–852

    Article  PubMed  Google Scholar 

  • Kennedy DO, Scholey AB (2006) The psychopharmacology of European herbs with cognition-enhancing properties. Curr Pharm 12:4613–4623

    Article  CAS  Google Scholar 

  • Kolak U, Kabouche A, Oztürk M, Kabouche Z, Topçu G, Ulubelen A (2009) Antioxidant diterpenoids from the roots of Salvia barrelieri. Phytochem Anal 20:320–327

    Article  PubMed  CAS  Google Scholar 

  • Kupchan SM, Karim A, Marcks C (1968) Taxodione and taxodone two novel diterpenoid quinone methide tumor inhibitors from Taxodium distichum. J Am Chem Soc 90:5923–5924

    Article  PubMed  CAS  Google Scholar 

  • Kuźma L, Wysokińska H, Różalski M et al (2012) Antimicrobial and anti-biofilm properties of new taxodione derivative from hairy roots of Salvia austriaca. Phytomedicine 19:1285–1287

    Article  PubMed  Google Scholar 

  • Lin Y, Liu A, Wu H, Westenbroek CH, Song Q, Yu H (2006) Salvianolic acid B an antioxidant from Salvia miltiorrhiza prevents Aβ-induced reduction in BPRP in PC12 cells. Biochem Biophys Res Commun 348:593–599

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Song XD, Liu W, Zhang TY, Zuo J (2003) Glucose deprivation induces mitochondrial dysfunction and oxidative stress in PC12 cell line. J Cell Mol Med 7:49–56

    Article  PubMed  CAS  Google Scholar 

  • Love S (1999) Oxidative stress in brain ischemia. Brain Pathol 9:119–131

    Article  PubMed  CAS  Google Scholar 

  • Marchev A, Haas C, Schulz S et al (2014) Sage in vitro cultures: a promising tool for the production of bioactive terpenes and phenolic substances. Biotechnol Lett 36:211–221

    Article  PubMed  CAS  Google Scholar 

  • Mousavi SH, Tayarani NZ, Parsaee H (2010a) Protective effect of saffron extract and crocin on reactive oxygen species mediated high glucose-induced toxicity in PC12 cells. Cell Mol Neurobiol 30:185–191

    Article  PubMed  CAS  Google Scholar 

  • Mousavi SH, Tayarani-Najaran Z, Asghari M, Sadeghnia HR (2010b) Protective effect of Nigella sativa extract and thymoquinone on serum/glucose deprivation-induced PC12 cells death. Cell Mol Neurobiol 30:591–598

    Article  PubMed  CAS  Google Scholar 

  • O’Brien J, Wilso I, Orton T, Pognan F (2000) Investigation of the alamar blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur J Biochem 267:5421–5426

    Article  PubMed  Google Scholar 

  • Pan H, Li D, Fang F et al (2011) Salvianolic acid A demonstrates cardioprotective effects in rat hearts and cardiomyocytes after ischemia/reperfusion injury. J Cardiovasc Pharm 58:535–542

    Article  CAS  Google Scholar 

  • Puyal J, Ginet V, Clarke PG (2013) Multiple interacting cell death mechanisms in the mediation of excitotoxicity and ischemic brain damage, a challenge for neuroprotection. Prog Neurobiol 105:24–48

    Article  PubMed  Google Scholar 

  • Rutherford D, Nielsen M, Tokutomi N, Akaike N (1994) Effects of plant diterpenes on the neuronal GABAA receptor-operated chloride current. Neuro Rep 5:2569–2572

    CAS  Google Scholar 

  • Samuni Y, Goldstein S, Dean OM, Berk M (2013) The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta 1830:4117–4129

    Article  PubMed  CAS  Google Scholar 

  • Seok JW, Doo YK, Byoung JG (2002) Cellular and molecular pathways of ischemic neuronal death. J Biochem Mol Biol 35:67–86

    Article  Google Scholar 

  • Shafer TJ, Atchison WD (1991) Transmitter, ion channel and receptor properties of pheochromocytoma (PC12) cells: a model for neurotoxicological studies. Neurotoxicology 12:473–492

    PubMed  CAS  Google Scholar 

  • Sims NR, Muyderman H (2010) Mitochondria oxidative metabolism and cell death in stroke. Biochim Biophys Acta 1802:80–91

    Article  PubMed  CAS  Google Scholar 

  • Tayarani-Najaran Z, Mousavi SH, Tajfard F et al (2013) Cytotoxic and apoptogenic properties of three isolated diterpenoids from Salvia chorassanica through bioassay-guided fractionation. Food Chem Toxicol 57:346–351

    Article  PubMed  CAS  Google Scholar 

  • Uttara B, Singh AV, Zamboni P, Mahajan RT (2009) Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 7:65–74

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Wan LM, Tan L, Wang ZR et al (2013) Preventive and therapeutic effects of Danhong injection on lipopolysaccharide induced acute lung injury in mice. J Ethnopharmacol 149:352–359

    Article  PubMed  Google Scholar 

  • Wang H, Joseph JA (1999) Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 27:612–616

    Article  PubMed  CAS  Google Scholar 

  • Won SH, Lee HJ, Jeong SJ et al (2010) Tanshinone IIA induces mitochondria dependent apoptosis in prostate cancer cells in association with an inhibition of phosphoinositide 3-kinase/AKT pathway. Biol Pharm Bull 33:1828–1834

    Article  PubMed  CAS  Google Scholar 

  • Wu YB, Ni ZY, Shi QW et al (2012) Constituents from Salvia species and their biological activities. Chem Rev 112:5967–6026

    Article  PubMed  CAS  Google Scholar 

  • Xu S, Little PJ, Lan T et al (2011) Tanshinone II-A attenuates and stabilizes atherosclerotic plaques in apolipoprotein-E knockout mice fed a high cholesterol diet. Arch Biochem Biophys 515:72–79

    Article  PubMed  CAS  Google Scholar 

  • Zaghloul AM, Gohar AA, Naiem ZA, Abdel-Bar FM (2008) Taxodione a DNA-binding compound from Taxodium distichum L. rich. Z Naturforsch C 63:355–360

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by Grants (No. 900996) from the Research Affairs of the Mashhad University of Medical Sciences as a part of a Pharm.D. thesis. We are also grateful for the editorial assistance of Mrs. Z. Gonzalez.

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There was no conflict of interest with other people or company.

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Correspondence to Zahra Tayarani-Najaran.

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Shafaei-Bajestani, N., Emami, S.A., Asili, J. et al. Anti-apoptotic Effect of Taxodione on Serum/Glucose Deprivation-Induced PC12 Cells Death. Cell Mol Neurobiol 34, 1103–1109 (2014). https://doi.org/10.1007/s10571-014-0085-2

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  • DOI: https://doi.org/10.1007/s10571-014-0085-2

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