Crocin acts as a neuroprotective mediator against methylphenidate‑induced neurobehavioral and neurochemical sequelae: Possible role of the CREB‑BDNF signaling pathway

• Autorzy: Ebrahimzadeh A. , Moghadam S.Y. , Rahimi H. , Motaghinejad M. , Motevalian M. , Safari S. , Mesrabadi M.A.
• Języki publikacji: EN

Abstrakty

EN

Methylphenidate (MPH) abuse causes adverse neurobehavioral and neurochemical effects. Some herbal components such as crocin have shown neuroprotective properties. The current study evaluates the potential role of the cyclic AMP response element binding protein (CREB)‑brain‑derived neurotrophic factor (BDNF) signaling pathway in mediating the neuroprotective effects of crocin against MPH‑induced neurotoxicity in rats. Seventy adult male rats were randomly divided into seven groups. Group 1 and 2 received 0.7 ml/rat of normal saline and 10 mg/kg of MPH, respectively. Groups 3, 4, 5, and 6 were treated simultaneously with MPH (10 mg/kg) and crocin (10, 20, 40, and 80 mg/kg, respectively) for 21 days. Group 7 was treated with crocin (80 mg/kg) alone for 21 days. The Morris water maze (MWM) and open field test were used to assess cognitive and locomotor activities. Hippocampal neurotoxicity parameters and levels of BDNF and CREB were evaluated. Simultaneous treatment with various doses of crocin reduced the MPH‑induced cognition disturbances and hyperlocomotion. In addition, lipid peroxidation increased with MPH treatment and levels of the oxidized forms of glutathione (GSSG), interleukin 1 beta (IL‑1β), tumor necrosis factor alpha (TNF‑α), and Bax increased. MPH treatment decreased levels of the reduced form of glutathione (GSH), P‑CREB, Bcl‑2, and BDNF in the hippocampus. MPH also reduced activity of superoxide dismutase, glutathione peroxidase, and glutathione reductase in the hippocampus. In contrast, crocin attenuated MPH‑induced oxidative stress, inflammation, and apoptosis, and increased levels of P‑CREB and BDNF. Thus, crocin – likely via stimulation of the P‑CREB/BDNF signaling pathway – displayed neuroprotection against MPH‑induced neurotoxicity

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: 4
• Opis fizyczny: p.352-366,fig.,ref.

Twórcy

autor

Ebrahimzadeh A.

• Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran

autor

Moghadam S.Y.

• Pharmaceutical Sciences Branch, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Chemistry, Islamic Azad University, Tehran, Iran

autor

Rahimi H.

• Pharmaceutical Sciences Branch, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Chemistry, Islamic Azad University, Tehran, Iran

autor

Motaghinejad M.

• Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran

autor

Motevalian M.

• Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
• Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

autor

Safari S.

• Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran

autor

Mesrabadi M.A.

• Department of Cellular and Molecular Biology, Faculity of Science, Isalamic Azad University of Karaj, Karaj, Iran

Bibliografia

• Andreazza AC, Frey BN, Valvassori SS, Zanotto C, Gomes KM, Comim CM, Cassini C, Stertz L, Ribeiro LC, Quevedo J (2007) DNA damage in rats after treatment with methylphenidate. Prog Neuropsychopharmacol Biol Psychiatry 31: 1282–1288.
• Arican, O, Aral M, Sasmaz S, Ciragil P (2005) Serum levels of TNF‑α, IFN‑γ, IL‑6, IL‑8, IL‑12, IL‑17, and IL‑18 in patients with active psoriasis and cor‑ relation with disease severity. Mediators Inflamm 2005: 273–279.
• Barbosa FJ, Hesse B, De Almeida RB, Baretta IP, Boerngen‑Lacerda R, Andreatini R (2011) Magnesium sulfate and sodium valproate block methylphenidate‑induced hyperlocomotion, an animal model of mania. Pharmacol Rep 63: 64–70.
• Barrett SP, Darredeau C, Bordy LE, Pihl RO (2005) Characteristics of meth‑ ylphenidate misuse in a university student sample. Can J Psychiatry 50: 457–461.
• Berridge CW, Devilbiss DM, Andrzejewski ME, Arnsten AF, Kelley AE, Schmeichel B, Hamilton C, Spencer RC (2006) Methylphenidate prefer‑ entially increases catecholamine neurotransmission within the prefron‑ tal cortex at low doses that enhance cognitive function. Biol Psychiatry 60: 1111–1120.
• Bethancourt JA, Camarena ZZ, Britton GB (2009) Exposure to oral methyl‑ phenidate from adolescence through young adulthood produces tran‑ sient effects on hippocampal‑sensitive memory in rats. Behav Brain Res 202: 50–57.
• Bors W, Michel C, Saran M (1984) Inhibition of the bleaching of the carot‑ enoid crocin a  rapid test for quantifying antioxidant activity. Biochim Biophys Acta ‑ Lipids And Lipid Metabolism 796: 312–319.
• Cao G, Zhu J, Zhong Q, Shi C, Dang Y, Han W, Liu X, Xu M, Chen T (2013) Distinct roles of methamphetamine in modulating spatial memory con‑ solidation, retrieval, reconsolidation and the accompanying changes of ERK and CREB activation in hippocampus and prefrontal cortex. Neuro‑ pharmacology 67: 144–154.
• Carlezon Jr WA, Duman RS, Nestler EJ (2005) The many faces of CREB. Trends Neurosci 28: 436–445.
• Chen Y, Zhang H, Tian X, Zhao C, Cai L, Liu Y, Jia L, Yin HX, Chen C (2008) Antioxidant potential of crocins and ethanol extracts of Gardenia jasminoides ELLIS and Crocus sativus L.: A relationship investigation between antioxidant activity and crocin contents. Food Chem 109: 484–492.
• Cheng J, Xiong Z, Duffney L, Liu S, Yan Z (2014a) Methylphenidate exerts dose‑dependent effects on glutamate receptors and cognitive behav‑ iors. Neurology 82: P4. 327.
• Cheng J, Xiong Z, Duffney LJ, Wei J, Liu A, Liu S, Chen GJ, Yan Z (2014b) Meth‑ ylphenidate exerts dose‑dependent effects on glutamate receptors and behaviors. Biol Psychiatry 76: 953–962.
• D’Hooge R, De Deyn PP (2001) Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev 36: 60–90.
• Demircan N, Safran B, Soylu M, Ozcan A, Sizmaz S (2006) Determination of vitreous interleukin‑1 (IL‑1) and tumor necrosis factor (TNF) levels in proliferative diabetic retinopathy. Eye 20: 1366–1369.
• El‑Beshbishy HA, Hassan MH, Aly HA, Doghish AS, Alghaithy AA (2012) Cro‑ cin “saffron” protects against beryllium chloride toxicity in rats through diminution of oxidative stress and enhancing gene expression of antiox‑ idant enzymes. Ecotoxicol Environ Saf 83: 47–54.
• El‑Maraghy SA, Rizk SM, Shahin NN (2015) Gastroprotective effect of crocin in ethanol‑induced gastric injury in rats. Chem Biol Interact 229: 26–35.
• Fagundes AO, Aguiar MR, Aguiar CS, Scaini G, Sachet MU, Bernhardt NM, Rezin GT, Valvassori SS, Quevedo J, Streck EL (2010) Effect of acute and chronic administration of methylphenidate on mitochondrial respirato‑ ry chain in the brain of young rats. Neurochem Res 35: 1675–1680.
• Firouzi M, Moshayedi P, Sabouni F, Parsa K, Keshavarz M (2010) The ef‑ fect of crocin (a derivative of Crocus sativus L.) on neural development and regeneration of rat: in vivo and in vitro study. Iran J Pharm Res 70: 70–81.
• Freese L, Muller E, Souza M, Couto‑Pereira N, Tosca C, Ferigolo M, Barro H (2012) GABA system changes in methylphenidate sensitized female rats. Behav Brain Res 231: 181–186.
• Gheita Ta, Kenawy SA (2014) Measurement of malondialdehyde, gluta‑ thione, and glutathione peroxidase in SLE patients. Methods Mol Biol 1134: 193–199.
• Goitia B, Raineri M, González Le, Rozas Jl, Garcia-Rill E, Bisagno V, Urbano FJ (2013) Differential effects of methylphenidate and cocaine on GABA transmission in sensory thalamic nuclei. J Neurochem 124: 602–612.
• Gould Td, Dao Dt, Kovacsics CE (2009) The open field test. Mood and anxi‑ ety related phenotypes in mice. Springer. Gray JD, Punsoni M, Tabori NE, Melton JT, Fanslow V, Ward MJ, Zupan B, Menzer D, Rice J, Drake CT (2007) Methylphenidate administration to ju‑ venile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress. J Neurosci 27: 7196–7207.
• Hattiangady B, Rao MS, Shetty GA, Shetty AK (2005) Brain‑derived neuro‑ trophic factor, phosphorylated cyclic AMP response element binding protein and neuropeptide Y decline as early as middle age in the den‑ tate gyrus and CA1 and CA3 subfields of the hippocampus. Exp Neurol 195: 353–371.
• Hosseinzadeh H, Karimi G, Niapoor M (2004) Antidepressant effects of Cro‑ cus sativus stigma extracts and its constituents, crocin and safranal, in mice. J Med Plants 3: 48–58.
• Hosseinzadeh H, Sadeghnia HR, Ghaeni FA, Motamedshariaty VS, Mohajeri SA (2012) Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic ce‑ rebral hypoperfusion in rats. Phytother Res 26: 381–386.
• Hosseinzadeh H, Sadeghnia HR, Ziaeent, Danaee A (2005) Protective ef‑ fect 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: 387–393.
• Hosseinzadeh H, Shamsaie F, Mehri S (2009) Antioxidant activity of aque‑ ous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituents, crocin and safranal. Pharmacogn Mag 5: 419–428.
• Hosseinzadeh H, Talebzadeh F (2005) Anticonvulsant evaluation of safran‑ al and crocin from Crocus sativus in mice. Fitoterapia 76: 722–724.
• Itzhak Y, Marti J (2002) Effect of the neuronal nitric oxide synthase inhibitor 7‑nitroindazole on methylphenidate‑induced hyperlocomotion in mice. Behav Pharmacol 13: 81–86.
• Jam IN, Sahebkar AH, Eslami S, Mokhber N, Nosrati  M, Khademi  M, Foroutan‑Tanha M, Ghayour‑Mobarhan M, Hadizadeh F, Ferns G (2017) The effects of crocin on the symptoms of depression in subjects with metabolic syndrome. Adv Clin Exp Med 26: 925–930.
• Jones Z, Dafny N (2013) Dose response effect of methylphenidate on ven‑ tral tegmental area neurons and animal behavior. Brain Res Bull 96: 86–92.
• Kanazawa LK, Vecchia DD, Wendler EM, De AS Hocayen P, Beirão Jr PS, De Mélo ML, Dos Reis Lívero FA, Corso CR, Stipp MC, Acco A (2017) Effects of acute and chronic quercetin administration on methylphenidate‑in‑ duced hyperlocomotion and oxidative stress. Life Sci 171: 1–8. Khalili  M, Hamzeh F (2010) Effects of active constituents of Crocus sati‑ vus  L., crocin on streptozocin‑induced model of sporadic Alzheimer’s disease in male rats. Iran Biomed J 14: 59–63.
• Khalili M, Roghan M, Ekhlasi M (2010) The effect of aqueous crocus sa‑ tivus  L. extract on intracerebroventricular streptozotocin‑induced cognitive deficits in rat: a  behavioral analysis. Iran J Pharm Res 17: 185–191.
• Kilkenny C, Browne W, Cuthill I, Emerson M, Altram D (2010) Animal re‑ search: Reporting of in vivo experiments, National Centre for the Re‑ placement, Refinement and Reduction of Animals in Research. PLOS Biology 23: 41–49.
• Kim H (2005) Neuroprotective herbs for stroke therapy in traditional east‑ ern medicine. Neurol Res 27: 287–301.
• Kim Y, Teylan Ma, Baron M, Sands A, Nairn Ac, Greengard P (2009) Meth‑ ylphenidate‑induced dendritic spine formation and ΔFosB expression in nucleus accumbens. Proc Natl Acad Sci U S A 106: 2915–2920.
• Koracevic D, Koracevic G, Djordjevic V, Andrejevic S, Cosic V (2001) Meth‑ od for the measurement of antioxidant activity in human fluids. J Clin Pathol: 54: 356–361.
• Kumar Gp, Khanum F (2012) Neuroprotective potential of phytochemicals. Pharmacogn Rev 6: 81–90.
• Lagace DC, Yee JK, Bolaños CA, Eisch AJ (2006) Juvenile administration of methylphenidate attenuates adult hippocampal neurogenesis. Biol Psy‑ chiatry 60: 1121–1130.
• Lee BH, Kim H, Park SH, Kim YK (2007) Decreased plasma BDNF level in depressive patients. J Affect Disord 101: 239–244.
• Lee IA, Lee JH, Baek NI, Kim DH (2005) Antihyperlipidemic effect of crocin isolated from the fructus of Gardenia jasminoides and its metabolite crocetin. Biol Pharm Bull 28: 2106–2110.
• LEONARD BE, MCCARTAN D, WHITE J, KING DJ (2004) Methylphenidate: a review of its neuropharmacological, neuropsychological and adverse clinical effects. Hum Psychopharmacol 19: 151–180.
• Mard SA, Azad SM, Ahangarpoor A (2016) Protective effect of crocin on gastric mucosal lesions induced by ischemia‑reperfusion injury in rats. Iran J Pharm Res 15: 93–98.
• Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G, Sun YE (2003) DNA methylation‑related chromatin remodeling in activity‑dependent BDNF gene regulation. Science 302: 890–893.
• Martins Mr, Reinke A, Petronilho Fc, Gomes Km, Dal‑Pizzol F, Quevedo J (2006) Methylphenidate treatment induces oxidative stress in young rat brain. Brain Res 1078: 189–197.
• Mayr B, Montminy M (2001) Transcriptional regulation by the phosphoryla‑ tion‑dependent factor CREB. Nat Rev Mol Cell Biol 2: 599–609.
• Mehri S, Abnous K, Mousavi Sh, Shariaty Vm, Hosseinzadeh H (2012) Neu‑ roprotective effect of crocin on acrylamide‑induced cytotoxicity in PC12 cells. Cell Mol Neurobiol 32: 227–235.
• Morton Wa, Stockton GG (2000) Methylphenidate abuse and psychiatric side effects. Prim Care Companion J Clin Psychiatry 2: 159–165.
• Motaghinejad M, Motevalian M, Abdollahi M, Heidari M, Madjd Z (2017a) Topiramate confers neuroprotection against methylphenidate‑induced neurodegeneration in dentate gyrus and CA1 regions of Hippocampus via CREB/BDNF pathway in rats. Neurotox Res 31: 373–399.
• Motaghinejad  M, Motevalian  M, Babalouei F, Abdollahi  M, Heidari  M, Madjd Z (2017b) Possible involvement of CREB/BDNF signaling path‑ way in neuroprotective effects of topiramate against methylphenidate induced apoptosis, oxidative stress and inflammation in isolated hip‑ pocampus of rats: Molecular, biochemical and histological evidences. Brain Res Bull 132: 82–98.
• Motaghinejad M, Motevalian M, Falak R, Heidari M, Sharzad M Kalantari E (2016a) Neuroprotective effects of various doses of topiramate against methylphenidate‑induced oxidative stress and inflammation in isolated rat amygdala: the possible role of CREB/BDNF signaling pathway. J Neu‑ ral Transm 123: 1463–1477.
• Motaghinejad M, Motevalian M, Fatima S, Beiranvand T, Mozaffari S (2017c) Topiramate via NMDA, AMPA/kainate, GABAA and Alpha2 receptors and by modulation of CREB/BDNF and Akt/GSK3 signaling pathway exerts neuroprotective effects against methylphenidate‑induced neurotoxicity in rats. J Neural Transm 124: 1369–1387.
• Motaghinejad M, Motevalian M, Fatima S, Faraji F, Mozaffari S (2017d) The Neuroprotective effect of curcumin against nicotine‑induced neurotox‑ icity is mediated by CREB–BDNF signaling pathway. Neurochem Res 42: 2921–2932.
• Motaghinejad M, Motevalian M, Fatima S, Hashemi H, Gholami M (2017e) Curcumin confers neuroprotection against alcohol‑induced hippocam‑ pal neurodegeneration via CREB‑BDNF pathway in rats. Biomed Phar‑ macother 87: 721–740.
• Motaghinejad  M, Seyedjavadein Z, Motevalian  M, Asadi  M (2016b) The neuroprotective effect of lithium against high dose methylphenidate: possible role of BDNF. Neurotoxicology 56: 40–54.
• Naghizadeh B, Boroushaki Mt, Vahdati Mashhadian N, MansourI SMT (2008) Protective effects of crocin against cisplatin‑induced acute renal failure and oxidative stress in rats. Iran Biomed J 12: 93–100.
• Ochiai T, Ohno S, Soeda S, Tanaka H, Shoyama Y, Shimeno H (2004a) Cro‑ cin prevents the death of rat pheochromyctoma (PC‑12) cells by its antioxidant effects stronger than those of α‑tocopherol. Neurosci Lett 362: 61–64.
• Ochiai T, Soeda S, Ohno S, Tanaka H, Shoyama Y, Shimeno H (2004b) Cro‑ cin prevents the death of PC‑12 cells through sphingomyelinase‑cera‑ mide signaling by increasing glutathione synthesis. Neurochem Int 44: 321–330.
• Oruc S, Gönül Y, Tunay K, Oruc OA, Bozkurt MF, Karavelioğlu E, Bağcıoğlu E, Coşkun KS, Celik S (2016) The antioxidant and antiapoptotic effects of crocin pretreatment on global cerebral ischemia reperfusion injury in‑ duced by four vessels occlusion in rats. Life Sci 154: 79–86.
• Peles E, Schreiber S, Linzy S, Domani Y, Adelson M (2015) Differences in methylphenidate abuse rates among methadone maintenance treat‑ ment patients in two clinics. J Subst Abuse Treat 54: 44–49.
• Rameshrad M, Razavi Bm, Hosseinzadeh H (2018) Saffron and its deriva‑ tives, crocin, crocetin and safranal: a patent review. Expert Opin Ther Pat 28: 147–165.
• Rashedinia M, Lari P, Abnous K, Hosseinzadeh H (2015) Protective effect of crocin on acrolein‑induced tau phosphorylation in the rat brain. Acta Neurobiol Exp 75: 208–219.
• Razavi BM, Sadeghi M, Abnous K, Vahdati F, Hosseinzadeh H (2017) Study of the role of CREB, BDNF, and VGF neuropeptide in long term antide‑ pressant activity of crocin in the rat cerebellum. Iran J Pharm Res 16: 1452–1462.
• Scherer EB, Da Cunha MJ, Matté C, Schmitz F, Netto CA, Wyse AT (2010) Methylphenidate affects memory, brain‑derived neurotrophic factor immunocontent and brain acetylcholinesterase activity in the rat. Neu‑ robiol Learn Mem 94: 247–253.
• Schmitz F, Scherer Eb, Machado Fr, Da Cunha Aa, Tagliari B, Netto Ca, Wyse AT (2012) Methylphenidate induces lipid and protein damage in prefrontal cortex, but not in cerebellum, striatum and hippocampus of juvenile rats. Metab Brain Dis 27: 605–612.
• Shi Yq, Huang Tw, Chen Lm, Pan Xd, Zhang J, Zhu Yg, Chen XC (2010) Ginse‑ noside Rg1 attenuates amyloid‑β content, regulates PKA/CREB activity, and improves cognitive performance in SAMP8 mice. J Alzheimers Dis 19: 977–989.
• Tamaddonfard E, Hamzeh-Gooshchi N (2010) Effect of crocin on the mor‑ phine-induced antinociception in the formalin test in rats. Phytother Res 24: 410–413.
• Vendruscolo Lf, Izídio Gs, Takahashi Rn, Ramos A (2008) Chronic methyl‑ phenidate treatment during adolescence increases anxiety‑related be‑ haviors and ethanol drinking in adult spontaneously hypertensive rats. Behav Pharmacol 19: 21–27.
• Vorhees Cv, Williams MT (2006) Morris water maze: procedures for assess‑ ing spatial and related forms of learning and memory. Nat Protoc 1: 848–856.
• Wang Y, Han T, Zhu Y, Zheng Cj, Ming Ql, Rahman K, Qin LP (2010) Anti‑ depressant properties of bioactive fractions from the extract of Crocus sativus L. J Nat Med 64: 24–30.
• Wieckowski MR, Giorgi C, Lebiedzinska M, Duszynski J, Pinton P (2009) Iso‑ lation of mitochondria‑associated membranes and mitochondria from animal tissues and cells. Nat Protoc 4: 15821596.
• Yoo KM, Kim DO, Lee CY (2007) Evaluation of Differnet Methods of Antiox‑ idant Measurement. Food Sci Biotechnol 16: 7–11.
• Yoshii A, Constantine-Paton  M (2010) Postsynaptic BDNF-TrkB signal‑ ing in synapse maturation, plasticity, and disease. Dev Neurobiol 70: 304–322.
• Yousefsani Bs, Mehri S, Pourahmad J, Hosseinzadeh H (2018) Crocin pre‑ vents sub‑cellular organelle damage, proteolysis and apoptosis in rat hepatocytes: A justification for its hepatoprotection. Iran J Pharm Res 17: 553–562.

Identyfikatory

DOI

10.21307/ane‑2019‑033