مروری بر ترکیبات موثره گیاه زعفران و اثرات دارویی آن بر بیماریهای تحلیل برنده سیستم عصبی

Abe, K., Saito H. (2000). Effects of saffron extract and its constituent crocin on learning behaviour and long‐term potentiation. Phytotherapy Research, 14(3), 149-152.

Ahmad, A.S., Ansari, M.A., Ahmad, M., Saleem, S., Yousuf, S., Hoda, M.N., et al. (2005). Neuroprotection by crocetin in a hemi-parkinsonian rat model. Pharmacology Biochemistry and Behavior, 81 (4), 805–813.

Ahn, J.H., Hu, Y., Hernandez, M., Kim, J.R. (2011). Crocetin inhibits betaamyloid fibrillization and stabilizes beta-amyloid oligomers. Biochemical and Biophysical Research Communications,414(1), 79–83.

Akhondzadeh, S., Tahmacebi‐Pour, N., Noorbala, A.A., Amini, H., Fallah‐Pour, H., Jamshidi, A.H., Khani, M. (2005). Crocus sativus L. inthe treatment of mild to moderate depression: a double‐blind, randomizedand placebo‐controlled trial. Phytotherapy Research, 19(2),148-151.

Alonso G.L., Salinas, M.R., Garijo, J., Sánchez Fernández, M.A. (2001). Composition of crocin and picrocrocin from Spanish saffron (Crocus sativus L.). Journal of Food Quality, 24(3), 219–233.

Arabia, G., Grossardt, B.R., Geda, Y.E., Carlin, J.M., Bower, J.H., Ahlskog, J.E., et al. (2007). Increased risk of depressive and anxiety disorders in relatives of patients with Parkinson disease. Archives of general psychiatry, 64 (12), 1385–1392.

Asadi, F., Jamshidi, A.H., Khodagholi, F., Yans, A., Azimi, L., Faizi, M., et al. (2015). Reversal effects of crocin on amyloid beta-induced memory deficit: Modification of autophagy or apoptosis markers. Pharmacology Biochemistry and Behavior, 139, 47–58.

Asadollahi, M., Nikdokht, P., Hatef, B., Sadr, S.S., Sahraei, H., Assarzadegan, F., et al. (2019). Protective properties of the aqueous extract of saffron (Crocus sativus L.) in ischemic stroke, randomized clinical trial. Journal of ethnopharmacology, 238,111833.

Asalgoo, S., Jahromi, G. P., Meftahi, G. H., and Sahraei, H. (2015). Posttraumatic Stress Disorder (PTSD): Mechanisms and Possible Treatments. Neurophysiology, 47(6), 482–489.

Asalgoo, S., Jahromi, G.P., Hatef, B., and Sahraei, H. (2018). The Effect of Saffron Aqueous Extract and Crocin on PTSD Rat Models: The Focus on Learning and Spatial Memory. Journal of Advances in Medical and Biomedical Research, 26(119), 34–42.

Amiriyan, F., Mostafaie, A., Kargar, S. M. A. (2021). The Investigation of Genetic Diversity of Saffron (Crocus sativus L.)Ecotypes Traits under Chilling Stress. Journal of Saffron Research, 8(2), 191-206.

Atefi, M. (2007). Saffron (Chemistry, Control, Quality and Processing), Beinonahrein Publications.

Auxemery, Y., 2018. Post-traumatic psychiatric disorders: PTSD is not the only diagnosis. La Presse Médicale, 47(5), 423–430.

Barnham, K.J., Masters, C.L., Bush, A.I. (2004). Neurodegenerative diseases and oxidative stress. Nature reviews Drug discovery, 3(3), 205–214.

Basti, A.A., Moshiri E., Noorbala A.A., Jamshidi A.H., Abbasi S.H., Akhondzadeh S. (2007). Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: A pilot double-blind randomized trial. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 31 (2),439–42.

Beavers, K.M., Brinkley, T.E., Nicklas, B.J. (2010). Effect of exercise training on chronic inflammation. Clinica Chimica Acta, 411(11-12),785- 793.

Bhat, J.V., Broker, R. (1953). Riboflavine and thiamine contents of saffron, Crocus sativus linn. Nature, 172(4377), 544.

Bian, Y., Zhao, C., Lee, SM-Y. (2020). Neuroprotective potency of saffron against neuropsychiatric diseases, neurodegenerative diseases, and other brain disorders: from bench to bedside. Frontiers in Pharmacology, 11, 579052.

Bolhassani, A. (2018). Bioactive components of saffron and their pharmacological properties. Studies in natural products chemistry, Chapter 10:289-311.

Boskabady, M.H., and Farkhondeh, T. (2016). Antiinflammatory, Antioxidant, and Immunomodulatory Effects of Crocus sativus L. and its Main Constituents. Phytotherapy Research, 30(7), 1072–1094.

Chehaibi, K., Trabelsi, I., Mahdouani, K., Slimane, M.N. (2016). Correlation of oxidative stress parameters and inflammatory markers in ischemic stroke patients. Journal of Stroke and Cerebrovascular Diseases, 25(11), 2585–93.

Chen, L., Qi, Y., Yang, X. (2015). Neuroprotective effects of crocin against oxidative stress induced by ischemia/reperfusion injury in rat retina. Ophthalmic research, 54(3), 157-68.

Chi, S., Wang, C., Jiang, T., Zhu, X. C., Yu, J. T., Tan, L. (2015). The prevalence of depression in Alzheimer’s disease: a systematic review and meta-analysis. Current Alzheimer Research, 12(2), 189–198.

Chu, W.Z., Qian, C.Y. (2005). [Expressions of Abeta1-40, Abeta1-42, tau202, tau396 and tau404 after intracerebroventricular injection of streptozotocin in rats (Chinese)]. Di 1 Jun Yi Da Xue Xue Bao, 25(2),168-170, 173.

Dashti, R.M., Zeinali, F., Anvari, M., Hosseini, S.M. (2012). Saffron (Crocus sativus L.) extract prevents and improves D-galactose and NaNO2 induced memory impairment in mice. EXCLI journal, 11, 328–337.

Deslauriers, A.M., Afkhami-Goli, A., Paul, A.M., Bhat, R.K., Acharjee, S., Ellestad, K.K., et al. (2011). Neuroinflammation and endoplasmic reticulum stress are coregulated by crocin to prevent demyelination and neurodegeneration. The Journal of Immunology, 187(9), 4788–4799.

Eyo, U.B., Murugan, M., Wu, L.J. (2017). Microglia-Neuron Communication in Epilepsy. Glia, 65 (1), 5–18.

Fadai, F., Mousavi, B., Ashtari, Z., Ali beigi, N., Farhang, S., Hashempour, S., et al. (2014). Saffron aqueous extract prevents metabolic syndrome in patients with schizophrenia on olanzapine treatment: a randomized triple blind placebo controlled study. Pharmacopsychiatry, 47(4-5), 156–161.

Farjah, G.H., Salehi, S., Ansari, M.H., Pourheidar, B. (2017). Protective effect of Crocus sativus L.(Saffron) extract on spinal cord ischemia-reperfusion injury in rats. Iranian journal of basic medical sciences, 20(3), 334.

Shakeri, M., Aminifard, M.H., Behdani, M. A., Tabatabaei, S.J. (2021). Effects of Different Gibberellic Acid Levels and Corm Weight on Antioxidant Activity and Secondary Metabolites of Saffron (Crocus sativus L.). Journal of Saffron Research, 9(1),1-10.

Izanloo, A., Derakhshan, A., Alizadeh, Z., Behdani, M. A. (2019). Cormlet Production of Saffron (Crocus sativus L.) using in vitro Culture Techniques. Journal of Saffron Research, 6(2), 179-189.

Farkhondeh, T., Samarghandian, S. (2014). The effect of saffron (Crocus sativus L.) and its ingredients on the management of diabetes mellitus and dislipidemia. African Journal of Pharmacy and Pharmacology, 8(20), 541–549.

Finley, J. W., Gao, S. (2017). A perspective on Crocus sativus l. (saffron) constituent crocin: a potent water-soluble antioxidant and potential therapy for alzheimer’s disease. Journal of agricultural and food chemistry, 65(5), 1005–1020.

Garavanda, F., Rahaeec, S., Vahedikiad, N., Jafarie, M. (2019). Different techniques for extraction and micro/nanoencapsulation of saffron bioactive ingredients, Trends in Food Science & Technology, 89, 26–44.

Georgiadou, G., Tarantilis, P.A., Pitsikas, N. (2012). Effects of the active constituents of Crocus Sativus L., crocins, in an animal model of obsessive compulsive disorder. Neuroscience letters, 528(1), 27–30.

Ghadrdoost, B., Vafaei, A.A., Rashidy-Pour, A., Hajisoltani, R., Bandegi, A.R., Motamedi, F., Haghighi, S., Sameni, H.R., Pahlvan, S. (2011). 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. European Journal of Pharmacology, 667 (1–3), 222–9.

Ghaffari, S., Hatami, H., and Dehghan, G. (2015). Saffron ethanolic extract attenuates oxidative stress, spatial learning, and memory impairments induced by local injection of ethidium bromide. Research in Pharmaceutical Sciences, 10(3), 222–232.

Ghahghaei, A., Bathaie, S. Z., and Bahraminejad, E. (2012). Mechanisms of the effects of Crocin on aggregation and deposition of a beta 1-40 fibrils in alzheimer’s disease. International Journal of Peptide Research and Therapeutics, 18(4), 347–351.

Ghahghaei, A., Bathaie, S.Z., Kheirkhah, H., and Bahraminejad, E. (2013). The protective effect of crocin on the amyloid fibril formation of a beta 42 peptide in vitro. Cellular & molecular biology letters, 18(3), 328–339.

Ghasemi, T., Abnous, K., Vahdati, F., Mehri, S., Razavi, B., Hosseinzadeh, H. (2015). Antidepressant effect of Crocus sativus aqueous extract and its effect on CREB, BDNF, and VGF transcript and protein levels in rat hippocampus. Drug Research, 65 (7),337–43.

Gracia-Garcia, P., de-la-Camara, C., Santabarbara, J., Lopez-Anton, R., Quintanilla, M.A., Ventura, T., et al. (2015). Depression and incident Alzheimer disease: the impact of disease severity. The American Journal of Geriatric Psychiatry, 23(2), 119–129.

Gudarzi, S., Jafari, M., Pirzad Jahromi, G., Eshrati, R., Asadollahi, M., Nikdokht, P. (2020). Evaluation of modulatory effects of saffron (Crocus sativus L.) aqueous extract on oxidative stress in ischemic stroke patients: A randomized clinical trial. Nutritional Neuroscience, 1–10,

Hasanpour, M., Ashrafi, M., Erjaee, H., Nazifi, S. (2018). The effect of saffron aqueous extract on oxidative stress parameters and important biochemical enzymes in the testis of streptozotocin-induced diabetic rats. Physiology and Pharmacology, 22(1), 28–37.

Hashtjini, M.M., Jahromi, G P., Meftahi, G.H., Esmaeili, D., Javidnazar, D. (2018). Aqueous extract of saffron administration along with amygdala deep brain stimulation promoted alleviation of symptoms in post-traumatic stress disorder (PTSD) in rats. Avicenna journal of phytomedicine, 8(4), 358–369.

Hatziagapiou, K., Kakouri, E., Lambrou, G.I., Bethanis, K., Tarantilis, P.A. (2019). Antioxidant properties of crocus sativus l. And its constituents and relevance to neurodegenerative diseases; focus on alzheimer’s and parkinson’s disease. Current Neuropharmacology, 17, 377-402

Hausenblas, H.A., Saha, D., Dubyak, P.J., Anton, S.D. (2013). Saffron (Crocus sativus L.) and major depressive disorder: A metaanalysis of randomized clinical trials. Journal of Integrative Medicine, 11 (6), 377–83.

He, W., Zhang, J., Xue, W., Hu, J., Wu, D., Chen N. (2009). Comparison of the action of isolichenin and methanol extract of saffron on long-term potentiation in hippocampal dentate gyrus in vivo. Yao xue xue bao= Acta Pharmaceutica Sinica, 44 (8), 858–62.

Hosseini, A., Razavi, B. M., Hosseinzadeh, H. (2018). Pharmacokinetic properties of saffron and its active components. European Journal of Drug Metabolism and Pharmacokinetics, 43(4), 383–390.

Hosseinzadeh ,H., Noraei, N.B. (2009). Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice. Phytotherapy Research, 23(6),768-74.

Hosseinzadeh, H., Khosravan, V. (2002). Anticonvulsant effects of aqueous and ethanolic extracts of Crocus sativus L. stigmas in mice. Archives of Iranian Medicine, 5(1), 44–47.

Hosseinzadeh, H., Modaghegh, M.H., Saffari, Z. (2009). Crocus sativus L. (saffron) extract and its active constituents (crocin and safranal) on ischemia-reperfusion in rat skeletal muscle. Evidence-Based Complementary and Alternative Medicine, 6(3), 343–350.

Hosseinzadeh, H., Sadeghnia, H.R. (2005). Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. Journal of Pharmacy and Pharmaceutical Sciences, 8(3), 394-399.

Hosseinzadeh, H., Sadeghnia, H.R. (2007). Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: involvement of GABAergic and opioids systems. Phytomedicine, 14(4), 256–262.

Hosseinzadeh, H., Sadeghnia, H.R., Ghaeni, F.A., Motamedshariaty, V.S., Mohajeri, S.A. (2012). Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats. Phytotherapy Research, 26(3), 381-386.

Hosseinzadeh, H., Talebzadeh F. (2005). Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia, 76 (7–8), 722–4.

Huang, A., Jia, L. (2019). Crocin enhances hypothermia therapy in hypoxic ischemia-induced brain injury in mice. Acta Neurologica Belgica, 1-8.

Icme, F., Erel, O., Avci, A., Satar, S., Gulen, M., Acehan, S. (2015). The relation between oxidative stress parameters, ischemic stroke, and hemorrhagic stroke. Turkish Journal of Medical Sciences, 45(4), 947–53.

Inoue, E., Shimizu, Y., Masui, R., Hayakawa, T., Tsubonoya, T., Hori, S., et al. (20180. Effects of saffron and its constituents, crocin-1, crocin-2, and crocetin on alphasynuclein fibrils. Journal of Natural Medicines, 72(1), 274–279.

Jahangiri, Z., Gholamnezhad, Z., Hosseini, M. (2019). Neuroprotective effects of exercise in rodent models of memory deficit and Alzheimer’s. Metabolic Brain Disease, 34(1),21-37.

Javadi, B., Sahebkar, A., Emami, S.A. (2013). A survey on saffron in major Islamic traditional medicine books. Iranian Journal of Basic Medical Sciences, 16(1), 1–11.

Karakani, A.M., Riazi, G., Mahmood Ghaffari, S., Ahmadian, S., Mokhtari, F., Jalili Firuzi, M., et al. (2015). Inhibitory effect of corcin on aggregation of 1N/4R human tau protein in vitro. Iranian Journal of Basic Medical Sciences, 18(5), 485–492.

Karimi, E., Oskoueian, E., Hendra, R., Jaafar, H.Z. (2010). Evaluation of Crocus sativus L. stigma phenolic and flavonoid compounds and its antioxidant activity. Molecules (Basel, Switzerland), 15 (9), 6244–56.

Khare, P., Chaudhary, S., Singh, L., Yadav, G., Verma, S. (2014). Evaluation of nootropic activity of Cressa cretica in scopolamineinduced memory impairment in mice. International Journal of Pharmacology and Toxicology, 2(2), 24–9.

Khazdair, M.R., Boskabady, M.H., Hosseini, M., Rezaee, R., Tsatsakis, A.M. (2015). The effects of Crocus sativus (saffron) and its constituents on nervous system: a review. Avicenna Journal of Phytomedicine, 5(5), 376–391.

Kong, Y., Kong, L.P., Luo, T., Li, G.W., Jiang, W., Li, S., et al. (2014). The Protective Effects of Crocetin on A beta (1-42)-Induced Toxicity in Ht22 Cells. CNS & Neurological Disorders - Drug Targets, 13(9), 1627–1632.

Lahmass, I., Ouahhoud, S., Elyoubi, M., Benabbas, R., Sabouni, A., Asehraou, A., et al. (2018). Evaluation of antioxidant activities of saffron stigma and spath as by-product of Crocus sativus L. MOJ Biology and Medicine, 3(4), 29.

Liakopoulou-Kyriakides, M., & Kyriakidis, D.A. (2002). Crocus sativus biological active constituents. Studies in Natural Products Chemistry, 26 (7), 293 - 312.

Lopresti, A.L., Drummond P.D. (2014). Saffron (Crocus sativus) for depression: A systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Human Psychopharmacology, 29 (6), 517–27.

Luo, S., Li, H., Mo, Z., Lei, J., Zhu, L., Huang, Y., et al. (2019). Connectivity map identifies luteolin as a treatment option of ischemic stroke by inhibiting MMP9 and activation of the PI3K/Akt signaling pathway. Experimental & Molecular Medicine, 51(3), 37.

Maggi L., S´anchez, A.M., Carmona, M., et al. (2011). Rapid determination of safranal in the quality control of saffron spice (Crocus sativus L.). Food Chemistry, 127(1), 369–373.

Maron, E., Nutt, D. (2017). Biological markers of generalized anxiety disorder. Dialogues in Clinical Neuroscience, 19(2), 147–158.

Mazumder, A.G., Sharma, P., Patial, V., Singh, D. (2017). Crocin Attenuates Kindling Development and Associated Cognitive Impairments in Mice via Inhibiting Reactive Oxygen Species-Mediated NF-kB Activation. Basic & Clinical Pharmacology & Toxicology, 120, 426–433.

Milanlioglu, A., Aslan, M., Ozkol, H., Çilingir, V., Aydın, M.N., Karadas, S. (2016). Serum antioxidant enzymes activities and oxidative stress levels in patients with acute ischemic stroke: influence on neurological status and outcome. Wien Klin Wochenschr, 128(5- 6), 169–174.

Mobarakeh, J. I., Fakhraei, N., Sadr, Z.A., Hamidipour, A., Mostafavi, E., Hosseini, R.H., Sardari, S. (2013). Effect of aqueous, ethanolic and acetonitrile Crocus sativus L. extracts on stress biomarkers in male rats. Journal of Medicinal Plants Research, 7,3269–79.

Mohammadzadeh, L., Hosseinzadeh, H., Abnous, K., and Razavi, B. M. (2018). Neuroprotective potential of crocin against malathion-induced motor deficit and neurochemical alterations in rats. Environmental Science and Pollution Research, 25(5), 4904–4914.

Moradi, K., Akhondzadeh, Sh. (2021). Psychotropic effects of saffron: a brief evidence-based overview of the interaction between a Persian herb and mental health. Journal of Iranian Medical Council, 4(2), 57-9.

 Moshiri, M., Vahabzadeh, M., Hosseinzadeh, H. (2015). Clinical Applications of Saffron (Crocus sativus) and its Constituents: A Review. Drug Research, 65(6), 287–295.

Mousavi, B., Bathaie, S. Z., Fadai, F., Ashtari, Z., Ali Beigi, N., Farhang, S., Hashempour, S., Shahhamzei, N.; Heidarzadeh, H. (2015). Safety evaluation of saffron stigma (Crocus sativus L.) aqueous extract and crocin in patients with schizophrenia. Avicenna Journal of Phytomedicine, 5(5), 413–419.

Mousavi, S.Z., Bathaie, S.Z. (2011). Historical uses of saffron: identifying potential new avenues for modern research. Avicenna Journal of Phytomedicine, 1(2), 57–66.

Murray, C.J., Lopez, A.D. (1997). Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet, 349 (9064), 1498–1504.

Naghibi, S.M., Hosseini, M., Khani, F., Rahimi, M., Vafaee, F., Rakhshandeh, H., et al. (2012). Effect of Aqueous Extract of Crocus sativus L. on Morphine-Induced Memory Impairment. Advances in Pharmacological Sciences, 494367.

Naghizadeh, B., Mansouri, M. T., Ghorbanzadeh, B., Farbood, Y., Sarkaki, A. (2013). Protective effects of oral crocin against intracerebroventricular streptozotocin-induced spatial memory deficit and oxidative stress in rats. Phytomedicine, 20(6), 537–542.

Nelson, J.C., Thase, M.E., Khan, A., Nelson, J.C. (2008). Are antidepressants effective? What’s a clinician to think?. Journal of Clinical Psychiatry, 69(6), 1014–1015.

Newport, D. J., Nemeroff, C. B. (2000). Neurobiology of posttraumatic stress disorder. Current Opinion in Neurobiology, 10(2), 211–218.

Niizuma, K., Yoshioka, H., Chen, H., Kim, G.S., Jung, J.E., Katsu, M., et al. (2010). Mitochondrial and apoptotic neuronal death signaling pathways in cerebral ischemia. Biochimica et Biophysica Acta, 1802(1), 92–99.

Ochiai, T., Ohno, S., Soeda, S., Tanaka, H., Shoyama, Y., and Shimeno, H. (2004). Crocin prevents the death of rat pheochromyctoma (PC-12) cells by its antioxidant effects stronger than those of alpha-tocopherol. Neuroscience Letters, 362(1), 61–64.

Ochiai, T., Shimeno, H., Mishima, K., Iwasaki, K., Fujiwara, M., Tanaka, H., et al. (2007). Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo. Biochimica et Biophysica Acta, 1770 (4), 578–584.

Pan, P.K., Qiao, L.Y., Wen, X.N. (2016). Safranal prevents rotenone-induced oxidative stress and apoptosis in an in vitro model of Parkinson’s disease through regulating Keap1/Nrf2 signaling pathway. Cellular and Molecular Biology, 62(14), 11– 17.

Papandreou, M.A., Kanakis, C.D., Polissiou, M.G., Efthimiopoulos, S., Cordopatis, P., Margarity, M., et al. (2006). Inhibitory activity on amyloidbeta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. Journal of Agricultural and Food Chemistry, 54(23), 8762–8768.

Pirzad Jahromi, G., Shabanzadeh Pirsaraei, A., Sadr, S.S., Kaka, G., Jafari, M., Seidi, S., et al. (2015). Multipotent bone marrow stromal cell therapy promotes endogenous cell proliferation following ischemic stroke. Clinical and Experimental Pharmacology and Physiology, 42(11), 1158–1167.

Pitsikas, N. (2016). Constituents of Saffron (Crocus sativus L.) as Potential Candidates for the Treatment of Anxiety Disorders and Schizophrenia. Molecules, 21(3), 303.

Pitsikas, N., Boultadakis, A., Georgiadou, G., Tarantilis, P., Sakellaridis, N. (2008). Effects of the active constituents of Crocus sativus L., crocins, in an animal model of anxiety. Phytomedicine, 15(12), 1135-1139.

Pitsikas, N., Tarantilis, P.A. (2017). Crocins, the active constituents of Crocus sativus L., counteracted apomorphine-induced performance deficits in the novel object recognition task, but not novel object location task, in rats. Neuroscience Letters, 644, 37–42.

Pontone, G.M., Williams, J.R., Anderson, K.E., Chase, G., Goldstein, S.A., Grill, S., et al. (2009). Prevalence of anxiety disorders and anxiety subtypes in patients with Parkinson’s disease. Movement Disorders Clinical Practice, 24(9), 1333–1338.

Purushothuman, S., Nandasena, C., Peoples, C.L., El Massri, N., Johnstone, D.M., Mitrofanis, J., et al. (2013). Saffron pre-treatment offers neuroprotection to Nigral and retinal dopaminergic cells of MPTP-Treated Mice. Journal of Parkinson's Disease, 3(1), 77–83.

Rao, S.V., Muralidhara, Yenisetti, S.C., and Rajini, P.S. (2016). Evidence of neuroprotective effects of saffron and crocin in a Drosophila model of Parkinsonism. Neurotoxicology, 52, 230–242.

Rashedinia, M., Lari, P., Abnous, K., and Hosseinzadeh, H. (2015). Protective effect of crocin on acrolein-induced tau phosphorylation in the rat brain. Acta Neurobiologiae Experimentalis, 75 (2), 208–219.

Rios, J.L., Recio, M., Giner, R., and Manez, S. (1996). An Update Review of Saffron and its Active Constituents. Phytotherapy Research, 10(3), 189–193.

Rodrigo, R., Fernandez-Gajardo, R., Gutierrez, R., Manuel Matamala, J., Carrasco, R., Miranda-Merchak, A., et al. (2013). Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities. CNS & Neurological Disorders - Drug Targets, 12(5), 698–714.

Ryan, M., Eatmon, C.V., and Slevin, J.T. (2019). Drug treatment strategies for depression in Parkinson disease. Expert Opinion on Pharmacotherapy, 20(11), 1351–1363.

Sadeghnia, H.R., Shaterzadeh, H., Forouzanfar, F., Hosseinzadeh, H. (2017). Neuroprotective effect of safranal, an active ingredient of Crocus sativus, in a rat model of transient cerebral ischemia. Folia Neuropathologica, 55(3), 206-213.

Sahraei, H., Fatahi, Z., Eidi, A., Haeri-Rohani, A., Hooshmandi, Z., Shekarforoush, S., et al. (2012). Inhibiting Post Traumatic Stress Disorder (PTSD) induced by electric shock using ethanol extract of saffron in rats. Journal of Biological Research, 18, 320–327.

Saleem, S., Ahmad, M., Ahmad, A.S., Yousuf, S., Ansari, M.A., Khan, M.B., Ishrat, T., Islam, F. (2006). Effect of saffron (Crocus sativus) on neurobehavioral and neurochemical changes in cerebral ischemia in rats.  Journal of Medicinal Food, 9(2), 246-53.

Samarghandian, S., Azimi-Nezhad, M., Samini, F., Farkhondeh, T. (2017). The role of saffron in attenuating agerelated oxidative damage in rat hippocampus. Recent Patents on Food, Nutrition & Agriculture, 8(3), 183–189.

Samarghandian, S., Borji, A. (2014). Anticarcinogenic effect of saffron (Crocus sativus L.) and its ingredients. Pharmacognosy Research, 6(2), 99–107

Samarghandian, S., Farkhondeh, T. (2020). Saffron and Neurological Disorders, in Saffron Elsevier, pp. 103–116.

Schrag, A., Taddei, R.N. (2017). Depression and Anxiety in Parkinson’s disease. International Review of Neurobiology, 133, 623–655.

Shirley, R., Ord, E., Work, L. (2014). Oxidative stress and the use of antioxidants in stroke. Antioxidants, 3(3), 472–501.

Sugiura, M., Shoyama, Y., Saito, H., Abe, K. (1995). The effects of ethanol and crocin on the induction of long-term potentiation in the CA1 region of rat hippocampal slices. The Japanese Journal of Pharmacology, 67(4), 395-7.

Sugiura, M., Shoyama, Y., Saito, H., Abe, K. (1995). The effects of ethanol and crocin on the induction of long-term potentiation in the CA1 region of rat hippocampal slices. The Japanese Journal of Pharmacology, 67(4), 395-397.

Tahvili, F., Ahmadi, M. (2020). Endurance Training With Saffron Extract on Plasma Levels in Alzheimer's Rats by Trimethyltin Chloride. Journal of Complementary Medicine Research, 10(2), 148-159.

Tamaddonfard, E., Farshid, A.A., Ahmadian, E., Hamidhoseyni, A. (2013). Crocin enhanced functional recovery after sciatic nerve crushinjury in rats. Iranian Journal of Basic Medical Sciences, 16 (1), 83–90.

Tamaddonfard, E., Gooshchi, N.H., and Seiednejad-Yamchi, S. (2012). Central effect of crocin on penicillin-induced epileptiform activity in rats. Pharmacological Reports, 64(1), 94–101.

Vakili, A., Einali, M.R., Bandegi, A.R. (2014). Protective effect of crocin against cerebral ischemia in a dose-dependent manner in a rat model of ischemic stroke. Journal of Stroke & Cerebrovascular Diseases, 23(1), 106-113.

Valavi, M., Zarban, A., Firuzabadi, M.D., Sharifzadeh, G., Zarezade, M. (2016). Oxidative stress and antioxidant markers in serum and red blood cell of patients with ischemic and hemorrhagic stroke: a case-control study. Modern Care Journal, 13(3), 10340.

Van der Mussele, S., Bekelaar, K., Le Bastard, N., Vermeiren, Y., Saerens, J., Somers, N., et al. (2013). Prevalence and associated behavioral symptoms of depression in mild cognitive impairment and dementia due to Alzheimer’s disease. International Journal of Geriatric Psychiatry, 28(9), 947–958.

Vecchio, L.M., Meng, Y., Xhima, K., Lipsman, N., Hamani, C., Aubert, I. (2018). The neuroprotective effects of exercise: Maintaining a healthy brain throughout aging. Brain Plasticity, 4(1):17-52.

Wang, Y., Han, T., Zhu, Y., Zheng, C.J., Ming, Q.L., Rahman, K., Qin, L.P. (2010). Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. Journal of Natural Medicines, 64 (1), 24–30.

Watson, P. (2019). PTSD as a Public Mental Health Priority. Current Psychiatry Reports, 21(7), 1–12.

Zandi, N., Pazoki, B., Momeni Roudsari, N., Momeni Roudsari, N., Jamshidi, V., Momtaz, S., et al. (2021). Prospects of saffron and its derivatives in Alzheimer’s disease. Archives of Iranian Medicine, Mar 1, 24(3), 233-52.

Zhang, G.F., Zhang, Y., Zhao, G. (2015). Crocin protects PC12 cells against MPP+-induced injury through inhibition of mitochondrial dysfunction and ER stress. Neurochemistry International, 89, 101–110.

Zhang, P., Cui J., Mansooridara, S., Shahriyari Kalantari, A., Zangeneh, A., Zangeneh, M.M., Sadeghian, N., aslimi, P.T, Bayat, R., Şen, F. (2020). Suppressor capacity of copper nanoparticles biosynthesized using Crocus sativus L. leaf aqueous extract on methadone‑induced cell death in adrenal phaeochromocytoma (PC12) cell line. Scientific Reports, 10,11631

Zheng, Y-Q., Liu, J-X., Wang, J-N., Xu, L. (2007). Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Research, 1138, 86-94.

Zitnanova, I., Siarnik, P., Kollar, B., Chomova, M., Pazderova, P., Andrezalova, L., et al. (2016). Oxidative stress markers and their dynamic changes in patients after acute ischemic stroke. Oxidative Medicine and Cellular Longevity, 9761697.