Planta Med 2023; 89(04): 364-376
DOI: 10.1055/a-1948-4378
Biological and Pharmacological Activity
Original Papers

PET Imaging and Neurohistochemistry Reveal that Curcumin Attenuates Brain Hypometabolism and Hippocampal Damage Induced by Status Epilepticus in Rats

Karla Slowing
1   Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain
,
Francisca Gomez
1   Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain
2   Brain Mapping Unit, Pluridisciplinary Institute, Complutense University of Madrid, Madrid, Spain
,
Mercedes Delgado
3   BIOIMAC, Complutense University of Madrid, Madrid, Spain
,
Rubén Fernández de la Rosa
2   Brain Mapping Unit, Pluridisciplinary Institute, Complutense University of Madrid, Madrid, Spain
3   BIOIMAC, Complutense University of Madrid, Madrid, Spain
,
Nira Hernández-Martín
2   Brain Mapping Unit, Pluridisciplinary Institute, Complutense University of Madrid, Madrid, Spain
,
Miguel Ángel Pozo
2   Brain Mapping Unit, Pluridisciplinary Institute, Complutense University of Madrid, Madrid, Spain
4   Department of Physiology, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain
5   Health Research Institute, Hospital Clínico San Carlos (IdISSC), Madrid, Spain
,
Luis García-García 
1   Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain
2   Brain Mapping Unit, Pluridisciplinary Institute, Complutense University of Madrid, Madrid, Spain
5   Health Research Institute, Hospital Clínico San Carlos (IdISSC), Madrid, Spain
› Author AffiliationsSupported by: Universidad Complutense de Madrid Fondo Específico de Investigación, FEI 16/45
Supported by: Ministerio de Ciencia e Innovación Retos PID2019-106968RB-100
› Further Information
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Abstract

Numerous preclinical studies provide evidence that curcumin, a polyphenolic phytochemical extracted from Curcuma longa (turmeric) has neuroprotective, anti-inflammatory and antioxidant properties against various neurological disorders. Curcumin neuroprotective effects have been reported in different animal models of epilepsy, but its potential effect attenuating brain glucose hypometabolism, considered as an early marker of epileptogenesis that occurs during the silent period following status epilepticus (SE), still has not been addressed. To this end, we used the lithium-pilocarpine rat model to induce SE. Curcumin was administered orally (300 mg/kg/day, for 17 days). Brain glucose metabolism was evaluated in vivo by 2-deoxy-2-[18F]Fluoro-D-Glucose ([18F]FDG) positron emission tomography (PET). In addition, hippocampal integrity, neurodegeneration, microglia-mediated neuroinflammation, and reactive astrogliosis were evaluated as markers of brain damage. SE resulted in brain glucose hypometabolism accompanied by body weight (BW) loss, hippocampal neuronal damage, and neuroinflammation. Curcumin did not reduce the latency time to the SE onset, nor the mortality rate associated with SE. Nevertheless, it reduced the number of seizures, and in the surviving rats, curcumin protected BW and attenuated the short-term glucose brain hypometabolism as well as the signs of neuronal damage and neuroinflammation induced by the SE. Overall, our results support the potential adaptogen-like effects of curcumin attenuating key features of SE-induced brain damage.

Key words

Curcumin - Curcuma longa - Zingiberaceae - lithium-pilocarpine model - [18F]FDG PET - neuroinflammation


Publication History

Received: 08 July 2022

Accepted after revision: 21 September 2022

Accepted Manuscript online:
21 September 2022

Article published online:
27 October 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Akhila KS, Gopi S. CHAPTER 1: Turmeric – The Miraculous Herb from Ancient India and its Historical Background. In: Gopi S, Thomas S, Kunnumakkara AB, Aggarwal BB, Amalraj A. eds. Food Chemistry, Function and Analysis. Cambridge: Royal Society of Chemistry; 2021: 1-29
    Google Scholar
  • 2 Prasad S, Aggarwal BB. Turmeric, the Golden Spice: From Traditional Medicine to Modern Medicine. In: Benzie IFF, Wachtel-Galor S. eds. Herbal Medicine: Biomolecular and Clinical Aspects: 2nd Edition. Boca Raton (FL): CRC Press/Taylor & Francis; 2011: 263-288
    Google Scholar
  • 3 Noorafshan A, Ashkani-Esfahani S. A review of therapeutic effects of curcumin. Curr Pharm Des 2013; 19: 2032-2046 DOI: 10.2174/138161213805289273.
    CrossrefPubMedGoogle Scholar
  • 4 Benameur T, Giacomucci G, Panaro MA, Ruggiero M, Trotta T, Monda V, Pizzolorusso I, Lofrumento DD, Porro C, Messina G. New promising therapeutic avenues of curcumin in brain diseases. Molecules 2021; 27: 236 DOI: 10.3390/molecules27010236.
    CrossrefPubMedGoogle Scholar
  • 5 Kunnumakkara AB, Bordoloi D, Padmavathi G, Monisha J, Roy NK, Prasad S, Aggarwal BB. Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases. Br J Pharmacol 2017; 174: 1325-1348 DOI: 10.1111/bph.13621.
    CrossrefPubMedGoogle Scholar
  • 6 Curia G, Lucchi C, Vinet J, Gualtieri F, Marinelli C, Torsello A, Costantino L, Biagini G. Pathophysiogenesis of mesial temporal lobe epilepsy: Is prevention of damage antiepileptogenic?. Curr Med Chem 2014; 21: 663-688 DOI: 10.2174/0929867320666131119152201.
    CrossrefPubMedGoogle Scholar
  • 7 Janszky J, Janszky I, Schulz R, Hoppe M, Behne F, Pannek HW, Ebner A. Temporal lobe epilepsy with hippocampal sclerosis: Predictors for long-term surgical outcome. Brain 2005; 128: 395-404 DOI: 10.1093/brain/awh358.
    CrossrefPubMedGoogle Scholar
  • 8 Tang F, Hartz AMS, Bauer B. Drug-resistant epilepsy: Multiple hypotheses, few answers. Front Neurol 2017; 8: 301 DOI: 10.3389/FNEUR.2017.00301.
    CrossrefPubMedGoogle Scholar
  • 9 Dhir A. Curcumin in epilepsy disorders. Phytother Res 2018; 32: 1865-1875 DOI: 10.1002/ptr.6125.
    CrossrefPubMedGoogle Scholar
  • 10 Martinc B, Grabnar I, Vovk T. Antioxidants as a preventive treatment for epileptic process: A review of the current status. Curr Neuropharmacol 2014; 12: 527-550 DOI: 10.2174/1570159x12666140923205715.
    CrossrefPubMedGoogle Scholar
  • 11 Gupta YK, Briyal S, Sharma M. Protective effect of curcumin against kainic acid induced seizures and oxidative stress in rats. Indian J Physiol Pharmacol 2009; 53: 39-46
    PubMedGoogle Scholar
  • 12 Jyoti A, Sethi P, Sharma D. Curcumin protects against electrobehavioral progression of seizures in the iron-induced experimental model of epileptogenesis. Epilepsy Behav 2009; 14: 300-308 DOI: 10.1016/j.yebeh.2008.11.011.
    CrossrefPubMedGoogle Scholar
  • 13 Agarwal NB, Jain S, Nagpal D, Agarwal NK, Mediratta PK, Sharma KK. Liposomal formulation of curcumin attenuates seizures in different experimental models of epilepsy in mice. Fundam Clin Pharmacol 2013; 27: 169-172 DOI: 10.1111/j.1472-8206.2011.01002.x.
    CrossrefPubMedGoogle Scholar
  • 14 Kaur H, Patro I, Tikoo K, Sandhir R. Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy. Neurochem Int 2015; 89: 40-50 DOI: 10.1016/j.neuint.2015.07.009.
    CrossrefPubMedGoogle Scholar
  • 15 Turski WA, Cavalheiro EA, Schwarz M, Czuczwar SJ, Kleinrok Z, Turski L. Limbic seizures produced by pilocarpine in rats: Behavioural, electroencephalographic and neuropathological study. Behav Brain Res 1983; 9: 315-335
    CrossrefPubMedGoogle Scholar
  • 16 Canto AM, Godoi AB, Matos AHB, Geraldis JC, Rogerio F, Alvim MKM, Yasuda CL, Ghizoni E, Tedeschi H, Veiga DFT, Henning B, Souza W, Rocha CS, Vieira AS, Dias EV, Carvalho BS, Gilioli R, Arul AB, Robinson RAS, Cendes F, Lopes-Cendes I. Benchmarking the proteomic profile of animal models of mesial temporal epilepsy. Ann Clin Transl Neurol 2022; 9: 454-467 DOI: 10.1002/acn3.51533.
    CrossrefPubMedGoogle Scholar
  • 17 Lévesque M, Biagini G, de Curtis M, Gnatkovsky V, Pitsch J, Wang S, Avoli M. The pilocarpine model of mesial temporal lobe epilepsy: Over one decade later, with more rodent species and new investigative approaches. Neurosci Biobehav Rev 2021; 130: 274-291
    CrossrefPubMedGoogle Scholar
  • 18 Lee EM, Park GY, Im KC, Kim ST, Woo CW, Chung JH, Kim KS, Kim JS, Shon YM, Kim YI, Kang JK. Changes in glucose metabolism and metabolites during the epileptogenic process in the lithium-pilocarpine model of epilepsy. Epilepsia 2012; 53: 860-869 DOI: 10.1111/j.1528-1167.2012.03432.x.
    CrossrefPubMedGoogle Scholar
  • 19 García-García L, Shiha AA, Fernández de la Rosa R, Delgado M, Silván Á, Bascuñana P, Bankstahl JP, Gomez F, Pozo MA. Metyrapone prevents brain damage induced by status epilepticus in the rat lithium-pilocarpine model. Neuropharmacology 2017; 123: 261-273 DOI: 10.1016/j.neuropharm.2017.05.007.
    CrossrefPubMedGoogle Scholar
  • 20 Shapiro LA, Wang L, Ribak CE. Rapid astrocyte and microglial activation following pilocarpine-induced seizures in rats. Epilepsia 2008; 49: 33-41 DOI: 10.1111/j.1528-1167.2008.01491.x.
    CrossrefPubMedGoogle Scholar
  • 21 Sarikaya I. PET studies in epilepsy. Am J Nucl Med Mol Imaging 2015; 5: 416-430
    PubMedGoogle Scholar
  • 22 Jiang Z, Guo M, Shi C, Wang H, Yao L, Liu L, Xie C, Pu S, LaChaud G, Shen J, Zhu M, Mu L, Ge H, Long Y, Wang X, Song Y, Sun J, Hou X, Zarringhalam A, Park SH, Shi C, Shen H, Lin Z. Protection against cognitive impairment and modification of epileptogenesis with curcumin in a post-status epilepticus model of temporal lobe epilepsy. Neuroscience 2015; 310: 362-371 DOI: 10.1016/j.neuroscience.2015.09.058.
    CrossrefPubMedGoogle Scholar
  • 23 Khadrawy YA, Sawie HG, Hosny EN. Neuroprotective effect of curcumin nanoparticles against rat model of status epilepticus induced by pilocarpine. J Complement Integr Med 2018; 15: 1-10 DOI: 10.1515/jcim-2017-0117.
    CrossrefPubMedGoogle Scholar
  • 24 Noor NA, Aboul Ezz HS, Faraag AR, Khadrawy YA. Evaluation of the antiepileptic effect of curcumin and Nigella sativa oil in the pilocarpine model of epilepsy in comparison with valproate. Epilepsy Behav 2012; 24: 199-206 DOI: 10.1016/j.yebeh.2012.03.026.
    CrossrefPubMedGoogle Scholar
  • 25 Wang J, Liu Y, Li XH, Zeng XC, Li J, Zhou J, Xiao B, Hu K. Curcumin protects neuronal cells against Status-Epilepticus-Induced hippocampal damage through induction of autophagy and inhibition of necroptosis. Can J Physiol Pharmacol 2017; 95: 501-509 DOI: 10.1139/cjpp-2016-0154.
    CrossrefPubMedGoogle Scholar
  • 26 Menon VP, Sudheer AR. Antioxidant and Anti-Inflammatory Properties of Curcumin. In: Aggarwal BB, Surh YJ, Shishodia S. eds. The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease. Boston, MA: Springer US; 2007: 105-125
    Google Scholar
  • 27 Aboul Ezz HS, Khadrawy YA, Noor NA. The neuroprotective effect of curcumin and Nigella sativa oil against oxidative stress in the pilocarpine model of epilepsy: A comparison with valproate. Neurochem Res 2011; 36: 2195-2204 DOI: 10.1007/s11064-011-0544-9.
    CrossrefPubMedGoogle Scholar
  • 28 Ahmad M. Protective effects of curcumin against lithium-pilocarpine induced status epilepticus, cognitive dysfunction and oxidative stress in young rats. Saudi J Biol Sci 2013; 20: 155-162 DOI: 10.1016/j.sjbs.2013.01.002.
    CrossrefPubMedGoogle Scholar
  • 29 Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. The essential medicinal chemistry of curcumin. J Med Chem 2017; 60: 1620-1637 DOI: 10.1021/acs.jmedchem.6b00975.
    CrossrefPubMedGoogle Scholar
  • 30 Fan F, Lei M. Mechanisms underlying curcumin-induced neuroprotection in cerebral ischemia. Front Pharmacol 2022; 13: 893118 DOI: 10.3389/fphar.2022.893118.
    CrossrefPubMedGoogle Scholar
  • 31 Di Meo F, Margarucci S, Galderisi U, Crispi S, Peluso G. Curcumin, gut microbiota, and neuroprotection. Nutrients 2019; 11: 1-14
    CrossrefPubMedGoogle Scholar
  • 32 Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: Problems and promises. Mol Pharm 2007; 4: 807-818 DOI: 10.1021/mp700113r.
    CrossrefPubMedGoogle Scholar
  • 33 Kiasalari Z, Roghani M, Khalili M, Rahmati B, Baluchnejadmojarad T. Antiepileptogenic effect of curcumin on kainate-induced model of temporal lobe epilepsy. Pharm Biol 2013; 51: 1572-1578 DOI: 10.3109/13880209.2013.803128.
    CrossrefPubMedGoogle Scholar
  • 34 Her C, Venier-Julienne MC, Roger E. Improvement of curcumin bioavailability for medical applications. Med Aromat Plants (Los Angel) 2018; 7: 1-15 DOI: 10.4172/2167-0412.1000326.
    CrossrefPubMedGoogle Scholar
  • 35 Hu L, Shi Y, Li JH, Gao N, Ji J, Niu F, Chen Q, Yang X, Wang S. Enhancement of oral bioavailability of curcumin by a novel solid dispersion system. AAPS PharmSciTech 2015; 16: 1327-1334 DOI: 10.1208/s12249-014-0254-0.
    CrossrefPubMedGoogle Scholar
  • 36 Kiss L, Walter FR, Bocsik A, Veszelka S, Ozsvári B, Puskás LG, Szabó-Révész P, Deli MA. Kinetic analysis of the toxicity of pharmaceutical excipients cremophor EL and RH40 on endothelial and epithelial cells. J Pharm Sci 2013; 102: 1173-1181 DOI: 10.1002/jps.23458.
    CrossrefPubMedGoogle Scholar
  • 37 Du P, Tang HY, Li X, Lin HJ, Peng WF, Ma Y, Fan W, Wang X. Anticonvulsive and antioxidant effects of curcumin on pilocarpine-induced seizures in rats. Chin Med J (Engl) 2012; 125: 1975-1979
    PubMedGoogle Scholar
  • 38 Wong CH, Bleasel A, Wen L, Eberl S, Byth K, Fulham M, Somerville E, Mohamed A. The topography and significance of extratemporal hypometabolism in refractory mesial temporal lobe epilepsy examined by FDG-PET. Epilepsia 2010; 51: 1365-1373 DOI: 10.1111/j.1528-1167.2010.02552.x.
    CrossrefPubMedGoogle Scholar
  • 39 Ahmed Juvale II, Che Has AT. The evolution of the pilocarpine animal model of status epilepticus. Heliyon 2020; 6: e04557 DOI: 10.1016/J.HELIYON.2020.E04557.
    CrossrefPubMedGoogle Scholar
  • 40 Mehla J, Reeta KH, Gupta P, Gupta YK. Protective effect of curcumin against seizures and cognitive impairment in a pentylenetetrazole-kindled epileptic rat model. Life Sci 2010; 87: 596-603 DOI: 10.1016/j.lfs.2010.09.006.
    CrossrefPubMedGoogle Scholar
  • 41 Nascimento CP, Ferreira LO, da Silva ALM, da Silva ABN, Rodrigues JCM, Teixeira LL, Azevedo JEC, de Araujo DB, Hamoy AO, Gonçalves BH, Coelho BHO, Lopes DCF, Hamoy M. A combination of curcuma longa and diazepam attenuates seizures and subsequent hippocampal neurodegeneration. Front Cell Neurosci 2022; 16: 884813 DOI: 10.3389/fncel.2022.884813.
    CrossrefPubMedGoogle Scholar
  • 42 Gage M, Putra M, Gomez-Estrada C, Golden M, Wachter L, Gard M, Thippeswamy T. Differential impact of severity and duration of status epilepticus, medical countermeasures, and a disease-modifier, saracatinib, on brain regions in the rat diisopropylfluorophosphate model. Front Cell Neurosci 2021; 15: 772868 DOI: 10.3389/fncel.2021.772868.
    CrossrefPubMedGoogle Scholar
  • 43 Drion CM, Kooijman L, Chan D, Berkhout J, van Vliet EA, Wadman WJ, Gorter JA. No persistent effects of intracerebral curcumin administration on seizure progression and neuropathology in the kindling rat model for temporal lobe epilepsy. Epilepsy Res 2022; 181: 106873 DOI: 10.1016/j.eplepsyres.2022.106873.
    CrossrefPubMedGoogle Scholar
  • 44 Aubry AV, Khandaker H, Ravenelle R, Grunfeld IS, Bonnefil V, Chan KL, Cathomas F, Liu J, Schafe GE, Burghardt NS. A diet enriched with curcumin promotes resilience to chronic social defeat stress. Neuropsychopharmacology 2019; 44: 733-742 DOI: 10.1038/s41386-018-0295-2.
    CrossrefPubMedGoogle Scholar
  • 45 Ciftci O, Tanyildizi S, Godekmerdan A. Protective effect of curcumin on immune system and body weight gain on rats intoxicated with 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). Immunopharmacol Immunotoxicol 2010; 32: 99-104 DOI: 10.3109/08923970903164318.
    CrossrefPubMedGoogle Scholar
  • 46 Asai A, Miyazawa T. Dietary curcuminoids prevent high-fat diet-induced lipid accumulation in rat liver and epididymal adipose tissue. J Nutr 2001; 131: 2932-2935 DOI: 10.1093/jn/131.11.2932.
    CrossrefPubMedGoogle Scholar
  • 47 Duncan J. The current status of neuroimaging for epilepsy. Curr Opin Neurol 2003; 16: 163-164 DOI: 10.1097/01.wco.0000063765.15877.55.
    CrossrefPubMedGoogle Scholar
  • 48 OʼBrien TJ, Miles K, Ware R, Cook MJ, Binns DS, Hicks RJ. The cost-effective use of 18F-FDG PET in the presurgical evaluation of medically refractory focal epilepsy. J Nucl Med 2008; 49: 931-937 DOI: 10.2967/jnumed.107.048207.
    CrossrefPubMedGoogle Scholar
  • 49 García-García L, Fernández de la Rosa R, Delgado M, Silván Á, Bascuñana P, Bankstahl JP, Gomez F, Pozo MA. Metyrapone prevents acute glucose hypermetabolism and short-term brain damage induced by intrahippocampal administration of 4-aminopyridine in rats. Neurochem Int 2018; 113: 92-106 DOI: 10.1016/j.neuint.2017.11.018.
    CrossrefPubMedGoogle Scholar
  • 50 Bascuñana P, García-García L, Javela J, Fernández de la Rosa R, Shiha AA, Kelly J, Delgado M, Pozo MÁ. PET neuroimaging reveals serotonergic and metabolic dysfunctions in the hippocampal electrical kindling model of epileptogenesis. Neuroscience 2019; 409: 101-110 DOI: 10.1016/j.neuroscience.2019.04.028.
    CrossrefPubMedGoogle Scholar
  • 51 Bascuñana P, Wolf BJ, Jahreis I, Brackhan M, García-García L, Ross TL, Bengel FM, Bankstahl M, Bankstahl JP. (99 m)Tc-HMPAO SPECT imaging reveals brain hypoperfusion during status epilepticus. Metab Brain Dis 2021; 36: 2597-2602 DOI: 10.1007/s11011-021-00843-z.
    CrossrefPubMedGoogle Scholar
  • 52 Shultz SR, Cardamone L, Liu YR, Hogan RE, Maccotta L, Wright DK, Zheng P, Koe A, Gregoire MC, Williams JP, Hicks RJ, Jones NC, Myers DE, OʼBrien TJ, Bouilleret V. Can structural or functional changes following traumatic brain injury in the rat predict epileptic outcome?. Epilepsia 2013; 54: 1240-1250 DOI: 10.1111/epi.12223.
    CrossrefPubMedGoogle Scholar
  • 53 Deleye S, Verhaeghe J, Wyffels L, Dedeurwaerdere S, Stroobants S, Staelens S. Towards a reproducible protocol for repetitive and semi-quantitative rat brain imaging with 18 F-FDG: Exemplified in a memantine pharmacological challenge. Neuroimage 2014; 96: 276-287 DOI: 10.1016/j.neuroimage.2014.04.004.
    CrossrefPubMedGoogle Scholar
  • 54 Deleye S, Waldron AM, Richardson JC, Schmidt M, Langlois X, Stroobants S, Staelens S. The effects of physiological and methodological determinants on 18F-FDG mouse brain imaging exemplified in a double transgenic alzheimer model. Mol Imaging 2016; 15: 1536012115624919 DOI: 10.1177/1536012115624919.
    CrossrefPubMedGoogle Scholar
  • 55 Schmued LC. Development and application of novel histochemical tracers for localizing brain connectivity and pathology. Brain Res 2016; 1645: 31-35
    CrossrefPubMedGoogle Scholar
  • 56 Schmued LC, Stowers CC, Scallet AC, Xu L. Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons. Brain Res 2005; 1035: 24-31 DOI: 10.1016/J.BRAINRES.2004.11.054.
    CrossrefPubMedGoogle Scholar
  • 57 He Q, Jiang L, Man S, Wu L, Hu Y, Chen W. Curcumin reduces neuronal loss and inhibits the NLRP3 inflammasome activation in an epileptic rat model. Curr Neurovasc Res 2018; 15: 186-192 DOI: 10.2174/1567202615666180731100224.
    CrossrefPubMedGoogle Scholar
  • 58 Barker-Haliski ML, Löscher W, White HS, Galanopoulou AS. Neuroinflammation in epileptogenesis: Insights and translational perspectives from new models of epilepsy. Epilepsia 2017; 58: 39-47 DOI: 10.1111/epi.13785.
    CrossrefPubMedGoogle Scholar
  • 59 Zhang L, Hu K, Shao T, Hou L, Zhang S, Ye W, Josephson L, Meyer JH, Zhang MR, Vasdev N, Wang J, Xu H, Wang L, Liang SH. Recent developments on PET radiotracers for TSPO and their applications in neuroimaging. Acta Pharm Sin B 2021; 11: 373-393
    CrossrefPubMedGoogle Scholar
  • 60 Li F, Xia Y, Meiler J, Ferguson-Miller S. Characterization and modeling of the oligomeric state and ligand binding behavior of purified translocator protein 18 kDa from Rhodobacter sphaeroides. Biochemistry 2013; 52: 5884-5899 DOI: 10.1021/BI400431T.
    CrossrefPubMedGoogle Scholar
  • 61 He Y, Yue Y, Zheng X, Zhang K, Chen S, Du Z. Curcumin, inflammation, and chronic diseases: How are they linked?. Molecules 2015; 20: 9183-9213 DOI: 10.3390/MOLECULES20059183.
    CrossrefPubMedGoogle Scholar
  • 62 Ghosh SS, Gehr TWB, Ghosh S. Curcumin and chronic kidney disease (CKD): Major mode of action through stimulating endogenous intestinal alkaline phosphatase. Molecules 2014; 19: 20139-20156 DOI: 10.3390/molecules191220139.
    CrossrefPubMedGoogle Scholar
  • 63 Mani BK, Osborne-Lawrence S, Metzger N, Zigman JM. Lowering oxidative stress in ghrelin cells stimulates ghrelin secretion. Am J Physiol Endocrinol Metab 2020; 319: E330-E337 DOI: 10.1152/AJPENDO.00119.2020.
    CrossrefPubMedGoogle Scholar
  • 64 Xu L, Li Z, Guo F. Curcumin improves expression of ghrelin through attenuating oxidative stress in gastric tissues of streptozotocin-induced diabetic gastroparesis rats. Eur J Pharmacol 2013; 718: 219-225 DOI: 10.1016/j.ejphar.2013.08.030.
    CrossrefPubMedGoogle Scholar
  • 65 Lucchi C, Curia G, Vinet J, Gualtieri F, Bresciani E, Locatelli V, Torsello A, Biagini G. Protective but not anticonvulsant effects of Ghrelin and JMV-1843 in the pilocarpine model of status epilepticus. PLoS One 2013; 8: e72716 DOI: 10.1371/journal.pone.0072716.
    CrossrefPubMedGoogle Scholar
  • 66 Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 1972; 32: 281-294
    CrossrefPubMedGoogle Scholar
  • 67 Foucault-Fruchard L, Doméné A, Page G, Windsor M, Emond P, Rodrigues N, Dollé F, Damont A, Buron F, Routier S, Chalon S, Antier D. Neuroprotective effect of the alpha 7 nicotinic receptor agonist PHA 543613 in an in vivo excitotoxic adult rat model. Neuroscience 2017; 356: 52-63 DOI: 10.1016/j.neuroscience.2017.05.019.
    CrossrefPubMedGoogle Scholar