11- Department of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, I. R. Iran
23- Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, I. R. Iran
34- Neuroscience Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, I. R. Iran
Objective: Several phytochemical agents have been known to exhibit a neuroprotective effect. Among them, curcumin, linalool, rutin, safranal, and thymoquinonewere widely investigated and neuroprotective activity of each of them was shown by several studies. This work was planned to investigate whether different combinations of them could induce better neuroprotective effect against glucose/serum deprivation (GSD)-induced cytotoxicity. Materials and Methods: PC12 cells were cultivated for 8 h in GSD condition in both the absence and presence of curcumin, linalool, rutin, safranal, thymoquinone, or combinations of them. At the end of the experiment, the cell viability was determined using MTT assay. Results: The cells cultured in GSD condition showed a significant decrease in viability (28±1%) as compared with those cultured in standard condition (100±2%). In the presence of curcumin (10 µg/ml), linalool (16 µg/ml), rutin (200 µg/ml), safranal (50 µg/ml), and thymoquinone (1 µg/ml), the cell viability increased to 69±3.4% (p<0.001), 44±1.4% (p<0.01), 64±0.5% (p<0.001), 49±2% (p<0.001), and 70±3.2% (p<0.001), respectively. When different combinations of the agents were tested, the best cytoprotective activity was obtained from safranal + curcumin + thymoquinone (97±5%, pvs. untreated cells). Conclusions: The present study demonstrated that a combination of safranal + curcumin + thymoquinone can block GSD-induced cell death and has the potential to be considered for management of cerebral ischemia and neurodegenerative diseases.
Abdullaev FI, Riveron-Negrete L, Caballero-Ortegaa H, Manuel Hernandez J, Perez-Lopez I, Pereda-Miranda R, Espinosa-Aquirre JJ. 2003. Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.). Toxicol in Vitro, 17: 731-736.
Behravan J, Hosseinzadeh H, Rastgoo A, Malekshah OM, Hessani M. 2010. Evaluation of the cytotoxic activity of crocin and safranal using potato disc and brine shrimp assays. Physiol Pharmacol, 13: 397-403.
Batista PA, Werner MF, Oliveira EC, Burgos L, Pereira P, Brum LF, Story GM, Santos AR. 2010. The antinociceptive effect of (-)-linalool in models of chronic inflammatory and neuropathic hypersensitivity in mice. J Pain, 11: 1222-1229.
Devi SL, Kannappan S, Anuradha CV. 2007. Evaluation of in vitro antioxidant activity of Indian bay leaf, Cinnamomum tamala (Buch. -Ham.) T. Nees & Eberm using rat brain synaptosomes as model system. Indian J Exp Biol, 45: 778-784.
Elisabetsky E, Marschner J, Souza DO. 1995. Effects of Linalool on glutamatergic system in the rat cerebral cortex. Neurochem Res, 20: 461-465.
Fukui H, Toyoshima K, Komaki R. 2011. Psychological and neuroendocrinological effects of odor of saffron (Crocus sativus). Phytomedicine, 18: 726-730.
Ghorbani A, Rakhshandeh H, Asadpour E, Sadeghnia HR. 2011. Effects of Coriandrum sativum extracts on glucose/serum deprivation-induced neuronal cell death. Avicenna J Phytomed, 2: 4-9.
Hadjzadeh MR, Tavakol Afshari J, Ghorbani A, Shakeri MT. 2006. The effects of aqueous extract of garlic (Allium sativum L.) on laryngeal cancer cells (Hep-2) and L929 cells in vitro. J Med Plants, 5: 41-48.
Hosseinzadeh H, Abootorabi A, Sadeghnia HR. 2008. Protective effect of Crocus sativus stigma extract and crocin (trans-crocin 4) on methyl methanesulfonate-induced DNA damage in mice organs. DNA Cell Biol, 27: 657-664.
Hosseinzadeh H, Sadeghnia HR. 2005. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharmaceut Sci, 8: 394-399.
Hosseinzadeh H, Sadeghnia HR. 2007. Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: Involvement of GABAergic and opioids systems. Phytomed, 14: 256-262.
Janbaz KH, Saeed SA, Gilani AH. 2002. Protective effect of rutin on paracetamol- and CCl4-induced hepatotoxicity in rodents. Fitoterapia, 73: 557-563.
Khader M, Bresgn N, Eckl PM. 2009. In vitro toxicological properties of thymoquinone. Food Chem Toxicol, 47: 129-133.
Khan MM, Ahmad A, Ishrat T, Khuwaja G, Srivastawa P, Khan MB, Raza SS, Javed H, Vaibhav K, Khan A, Islam F. 2009. Rutin protects the neural damage induced by transient focal ischemia in rats. Brain Res, 1292: 123-135.
La Casa C, Villegas I, Alarcon de la Lastra C, Motilva V, Martin Calero MJ. 2000. Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions. J Ethnopharmacol, 71: 45-53.
Mendonca LM¸ da Silva Machado C, Correia Teixeira CC, Pedro do Freitas LA, Pires Bianchi MD, Greggi Antunes LM. 2012. Curcumin reduces cisplatin-induced neurotoxicity in NGF-differentiated PC12 cells. NeuroToxicol, In press.
Mortazavian SM, Ghorbani A. 2012. Antiproliferative effect of viola tricolor on neuroblastoma cells in vitro. Aust J Med Herbalism, 24: 93-96.
Mortazavian SM, Ghorbani A, Hesari TG. 2012. Effect of hydro-alcoholic extract of Viola tricolor and its fractions on proliferation of uterine cervix carcinoma cells. Iran J Obst Gynecol Infertil, 15: 9-16.
Mousavi SZ, Bathaie SZ. 2011. Historical uses of saffron: Identifying potential new avenues for modern. Avicenna J Phytomed, 1: 57-66.
Mousavi SH, Tayarani-Najaran Z, Asghari M, Sadeghnia HR. 2010a. Protective effect of Nigella sativa extract and thymoquinone on serum/glucose deprivation-induced PC12 cells death. Cell Mol Neurobiol, 30: 591-598.
Mousavi SH, Tayarani NZ, Parsaee H. 2010b. Protective effect of saffron extract and crocin on reactive oxygen species-mediated high glucose-induced toxicology in PC12 cells. Cell Mol Neurobiol, 30: 185-191.
Nassiri-Asl M, Shariati-Rad S, Zamansoltani F. 2008. Anticonvulsive effects of intracerebroventricular administration of rutin in rats. Prog Neuro-Psychopharmacol Biol Psychiatry, 32: 989-993.
Park SY, Kim HS, Cho EK, Kwon BY, Phark S, Hwang KW, Sul D. 2008. Curcumin protected PC12 cells against beta-amyloid-induced toxicity through the inhibition of oxidative damage and tau hyperphosphorylation. Food Chem Toxicol, 46: 2881-2887.
Pu F, Mishima K, Irie K, Motohashi K, Tanaka Y, Orito K, Egawa T, Kitamura Y, Egashira N, Iwasaki K, Fujiwara M. 2007. Neuroprotective effects of quercetin and rutin on spatial memory impairment in an 8-arm radial maze task and neuronal death induced by repeated cerebral ischemia in rats. J Pharmacol Sci, 104: 329-334.
Rakhshandeh H, Sadeghnia HR, Ghorbani A. 2012. Sleep-prolonging effect of Coriandrum sativum hydro-alcoholic extract in mice. Nat Prod Res 26: 2095-2098.
Rui PAN, Sheng QIU, Da-xiang LU, Jun DONG. 2008. Curcumin improves learning and memory ability and its neuroprotective mechanism in mice. Chin Med J, 121: 832-839.
Sadeghnia HR, Farahmand SK, Asadpur E, Rakhshandeh H, Ghorbani A. 2012. Neuroprotective effect of Lactuca sativa on glucose/serum deprivation-induced cell death. Afr J Pharm Pharmacol, 6: 2464-2471.
Tamaddonfard E. 2012. Turmeric active substance, curcumin, enhanced apomorphine-induced yawning in rats. Avicenna J Phytomed, In press.
Tamaddonfard E, Erfanparast A, Hamzeh-Gooshchi N, Yousofizadeh S. 2012. Effect of curcumin, the active constituent of turmeric, on penicillin-induced epileptiform activity in rats. Avicenna J Phytomed, 2: 196-205.
Tarantilis PA, Tsoupras G, Polissiou M. 1995. Determination of saffron (Crocus sativus L.) components in crude plant extract using highperformance liquid chromatography-UV-visiblephotodiode-array detection-mass spectrometry. J Chromatogra, 699: 107-118.