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Preventive effects of crocin on neuronal damages induced by D-galactose through AGEs and oxidative stress in human neuroblastoma cells (SH-SY5Y)

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Objective: D-galactose (D-gal) is well-known agent to induce aging process. In the present study, we selected crocin, the main constituent of Crocus sativus L. (saffron), against D-gal- induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Methods: Pretreated cells with crocin (25-500 μM, 24 h) were exposed to D-gal (25–400 mM, 48 h). The MTT assay was used for determination cell viability. Dichlorofluorescin diacetate assay (DCF-DA) and senescence associated β-galactosidase staining assay (SA- β-gal) were used to evaluate the generation of reactive oxygen species and beta-galactosidase as an aging marker, respectively. Also advanced glycation end products (AGEs) expression which is known as the main mechanism of age-related diseases was measured by western blot analysis. Results: The findings of our study showed that treatment of cells with D-gal (25-400 mM) for 48h decreased cell viability concentration dependency. Reactive oxygen species (ROS) levels which are known as main factors in age-related diseases increased from 100 ± 8% in control group to 132 ± 22% in D-gal (200 mM) treated cells for 48h. The cytotoxic effects of D-gal decreased with 24h crocin pretreatment of cells. The cell viability at concentrations of 100 μM, 200 μM and 500 μM increased and ROS production decreased at concentrations of 200 and 500 μM to 111.5 ± 6% and 108 ± 5%, respectively. Also lysosomal biomarker of aging and carboxymethyl lysine (CML) expression as an AGE protein, significantly increased in D-gal 200 mM group after 48h incubation compare to control group. Pretreatment of SHSY-5Y cells with crocin (500 μM) before adding D-gal significantly reduced aging marker and CML formation. Conclusion: Treatment of SH-SY5Y cells with crocin before adding of D-gal restored aging effects of D-gal concentration dependency. These findings indicate that crocin has potent anti- aging effects through inhibition of AGEs and ROS production.

Abstract

Objective: D-galactose (D-gal) is well-known agent to induce aging process. In the present study, we selected crocin, the main constituent of Crocus sativus L. (saffron), against D-gal- induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Methods: Pretreated cells with crocin (25-500 μM, 24 h) were exposed to D-gal (25–400 mM, 48 h). The MTT assay was used for determination cell viability. Dichlorofluorescin diacetate assay (DCF-DA) and senescence associated β-galactosidase staining assay (SA- β-gal) were used to evaluate the generation of reactive oxygen species and beta-galactosidase as an aging marker, respectively. Also advanced glycation end products (AGEs) expression which is known as the main mechanism of age-related diseases was measured by western blot analysis. Results: The findings of our study showed that treatment of cells with D-gal (25-400 mM) for 48h decreased cell viability concentration dependency. Reactive oxygen species (ROS) levels which are known as main factors in age-related diseases increased from 100 ± 8% in control group to 132 ± 22% in D-gal (200 mM) treated cells for 48h. The cytotoxic effects of D-gal decreased with 24h crocin pretreatment of cells. The cell viability at concentrations of 100 μM, 200 μM and 500 μM increased and ROS production decreased at concentrations of 200 and 500 μM to 111.5 ± 6% and 108 ± 5%, respectively. Also lysosomal biomarker of aging and carboxymethyl lysine (CML) expression as an AGE protein, significantly increased in D-gal 200 mM group after 48h incubation compare to control group. Pretreatment of SHSY-5Y cells with crocin (500 μM) before adding D-gal significantly reduced aging marker and CML formation. Conclusion: Treatment of SH-SY5Y cells with crocin before adding of D-gal restored aging effects of D-gal concentration dependency. These findings indicate that crocin has potent anti- aging effects through inhibition of AGEs and ROS production.

참고문헌 (41)

  1. Fried LP, "Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care", J Gerontol A Biol Sci Med Sci, 59(3), pp.255~263 (2004)[DOI]
  2. Nowotny K, "Advanced glycation end products and oxidative stress in type 2 diabetes mellitus", Biomolecules, 5(1), pp.194~222 (2015)[DOI]
  3. Li L, "Formation and inhibition of <TEX>$N{\varepsilon}$<", TEX>- (carboxymethyl)lysine in saccharide-lysine model systems during microwave heating, 2012, pp.17(11), 12758~12770
  4. Xu LQ, "Polydatin attenuates d-galactose- induced liver and brain damage through its anti-oxidative, anti-inflammatory and anti-apoptotic effects in mice", Food Funct, 7(11), pp.4545~4555 (2016)[DOI]
  5. Liu YY, "Hydrogen sulfide protects SH-SY5Y neuronal cells against d-galactose induced cell injury by suppression of advanced glycation end products formation and oxidative stress", Neurochemistry int, 62(5), pp.603~609 (2013)[DOI]
  6. Hsieh HM, "Soy isoflavones attenuate oxidative stress and improve parameters related to aging and Alzheimer's disease in C57BL", 6J mice treated with D-galactose, 2009, pp.47(3), 625~632
  7. Hu LF, "Neuroprotective effects of hydrogen sulfide on Parkinson's disease rat models", Aging cell, 9(2), pp.135~146 (2010)[DOI]
  8. Sadowska-Bartosz I, "Effect of antioxidants supplementation on aging and longevity", Biomed Res Int, 2014, pp.404680~ (2014)
  9. Head E, "Oxidative damage and cognitive dysfunction: antioxidant treatments to promote healthy brain aging", Neurochem res, 34(4), pp.670~678 (2009)[DOI]
  10. Abdullaev FI, "Biological effects of saffron", BioFactors (Oxford, England), 4(2), pp.83~86 (1993)
  11. Bostan HB, "Toxicology effects of saffron and its constituents", Iran J Basic Med Sci, 20(2), pp.110~121 (2017)
  12. Moshiri M, "Clinical applications of saffron (Crocus sativus) and its constituents: a review", Drug Res (Stuttq), 65(6), pp.287~295 (2015)
  13. Vahdati Hassani F, "Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus", Daru, 22(1), pp.16~ (2014)[DOI]
  14. Ochiai T, "Crocin prevents the death of rat pheochromyctoma (PC-12) cells by its antioxidant effects stronger than those of alpha- tocopherol", Neurosci Lett, 362(1), pp.61~64 (2004)[DOI]
  15. Abdullaev FI, "Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials", Cancer Detect Prev, 28(6), pp.426~432 (2004)[DOI]
  16. Samarghandian S, "Ameliorative effect of saffron aqueous extract on hyperglycemia, hyperlipidemia, and oxidative stress on diabetic encephalopathy in streptozotocin induced experimental diabetes mellitus", Biomed Res Int, 2014, pp.920857~ (2014)
  17. He SY, "Effect of crocin on experimental atherosclerosis in quails and its mechanisms", Life Sci, 77(8), pp.907~921 (2005)[DOI]
  18. Ding Q, "Anti-arthritic effects of crocin in interleukin-1beta-treated articular chondrocytes and cartilage in a rabbit osteoarthritic model", Inflamm res, 62(1), pp.17~25 (2013)[DOI]
  19. Ghadrdoost B, "Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats", Eur J Pharmacol, 667(1-3), pp.222~229 (2011)[DOI]
  20. Alavizadeh SH, "Bioactivity assessment and toxicity of crocin: a comprehensive review", Food Chem Toxicol, 64, pp.65~80 (2014)[DOI]
  21. Rashedinia M, "Protective effect of crocin on acrolein- induced tau phosphorylation in the rat brain", Acta Neurobiol Exp (Wars), 75(2), pp.208~219 (2015)
  22. Shirali S, "Effect of crocin on the insulin resistance and lipid profile of streptozotocin-induced diabetic rats", Phytother Res, 27(7), pp.1042~1047 (2013)[DOI]
  23. Hadizadeh F, "Extraction and purification of crocin from saffron stigmas employing a simple and efficient crystallization method", Pak J Biol Sci, 13(14), pp.691~698 (2010)[DOI]
  24. Liu YY, "Hydrogen sulfide protects amyloid-<TEX>${\beta}$<", TEX> induced cell toxicity in microglia, 2010, pp.22(4), 1189~1200
  25. Li Y, "Neuroprotective effects of chlorogenic acid against apoptosis of PC12 cells induced by methylmercury", Environ Toxicol Pharmacol, 26(1), pp.13~21 (2008)[DOI]
  26. Lee BY, "Senescence-associated <TEX>${\beta}$<", TEX>-galactosidase is lysosomal <TEX>${\beta}$<, Aging cell, pp.2006, 5(2)[DOI]
  27. Liu YY, "ACS84, a novel hydrogen sulfide-releasing compound, protects against amyloid <TEX>${\beta}$<", TEX>-induced cell cytotoxicity, 2011, pp.58(5), 591~598
  28. Yu S, "Isochaihulactone protects PC12 cell against H2O2 induced oxidative stress and exerts the potent anti-aging effects in D-galactose aging mouse model", Acta Pharmacol Sin, 31(12), pp.1532~1540 (2010)[DOI]
  29. Mehri S, "Neuroprotective effect of crocin on acrylamide-induced cytotoxicity in PC12 cells", Cell Mol Neurobiol, 32(2), pp.227~235 (2012)[DOI]
  30. Hosseinzadeh H, "Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituents, crocin and safranal", Pharmacog Mag, 5(20), pp.419~424 (2009)
  31. Dimri GP, "A biomarker that identifies senescent human cells in culture and in aging skin in vivo", Proceedings of the National Academy of Sciences, 92(20), pp.9363~9367 (1995)[DOI]
  32. Song YS, "Dinstinct ROS and biochemical profiles in cells undergoing DNA damage-induced senescence and apoptosis", Mech Ageing Dev, 126(5), pp.580~590 (2005)[DOI]
  33. Liochev SI, "Reactive oxygen species and the free radical theory of aging", Free Radic Biol Med, 60, pp.1~4 (2013)[DOI]
  34. Hosseinzadeh H, "Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemia-reperfusion- induced oxidative damage in rats", J Pharm Pharm Sci, 8(3), pp.387~393 (2005)
  35. Hosseinzadeh H, "Crocus sativus L.(Saffron) extract and its active constituents (crocin and safranal) on ischemia-reperfusion in rat skeletal muscle", Evid Based Complement Alternat Med, 6(3), pp.343~350 (2009)[DOI]
  36. Mousavi SH, "Protective effect of saffron extract and crocin on reactive oxygen species-mediated high glucose-induced toxicity in PC12 cells", Cell Mol Neurobiol, 30(2), pp.185~191 (2010)[DOI]
  37. Chen L, "Neuroprotective effects of crocin against oxidative stress induced by ischemia", reperfusion injury in rat retina, 2015, pp.54(3), 157~168
  38. Haider S, "A high dose of short term exogenous D-galactose administration in young male rats produces symptoms simulating the natural aging process", Life Sci, 124, pp.110~119 (2015)[DOI]
  39. Kuhla A, "Advanced glycation end products are mitogenic signals and trigger cell cycle reentry of neurons in Alzheimer's disease brain", Neurobiol Aging, 36(2), pp.753~761 (2015)[DOI]
  40. Pertynska-Marczewska M, "Advanced glycation end products upregulate angiogenic and pro-inflammatory cytokine production in human monocyte", macrophages, 2004, pp.28(1), 35~47
  41. Tha KK, "Changes in expressions of proinflammatory cytokines IL-<TEX>$1{\beta}$<", TEX>, TNF-<TEX>${\alpha}$<, Brain res, pp.2000, 885(1)[DOI]

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