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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Research Article

Hypericin Ameliorates Maternal Separation-Induced Cognitive Deficits and Hippocampal Inflammation in Rats

Author(s): Sedigheh Khanjani Jolodar, Mohammadreza Bigdeli* and Akbar Hajizadeh Moghaddam

Volume 21, Issue 9, 2021

Published on: 27 July, 2020

Page: [1144 - 1149] Pages: 6

DOI: 10.2174/1389557520666200727154453

Price: $65

Abstract

Background and Objective: Maternal separation as an epigenetic agent provokes a severe change in the brain, such as inflammation response, which is a key risk factor for the progression of autism spectrum disorders (ASD). This study evaluated the preventive effect of hypericin on maternal separation-induced cognitive deficits and hippocampal inflammation.

Methods: Here, we reported that pups are subjected to maternal separations for 1 h per day from postnatal days (PND) 1-9 displayed apparent memory impairment in young rats (postnatal day 34) compared to controls group. Furthermore, maternal separation significantly increased inflammation factors in the hippocampus area. Anti-inflammation constituent shed light on treating ASD.

Results: In this study, we found that treatment with hypericin (10 and 50 mg/kg) significantly suppresses expression of hippocampal interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the maternal separation rat model. Also, we found that hypericin prevented the decrease of hippocampal dopamine levels in the offspring of maternal separation rats.

Conclusion: The data indicated that hypericin may play a neuroprotective role in hippocampal cell and ameliorates dysfunctions in memory and level of inflammation factor in this autism model. Thus, hypericin could be used as an intervention for treating ASD.

Keywords: Maternal separation, autism, inflammation, memory, hypericin, hippocampus.

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[1]
Yamasue, H.; Domes, G. Oxytocin and autism spectrum disorders. InBehavioral Pharmacology of Neuropeptides: Oxytocin; Springer: Cham, 2017, pp. 449-465.
[http://dx.doi.org/10.1007/7854_2017_24]
[2]
Poletaev, AB; Shenderov, BA Autism: Genetics or epigenetics. P. Weerkamp Bartholomeus, Autism: Is there a place for ReAttach Therapy.,, 2018, 123-134.
[3]
Gao, J.; Wang, X.; Sun, H.; Cao, Y.; Liang, S.; Wang, H.; Wang, Y.; Yang, F.; Zhang, F.; Wu, L. Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model. Int. J. Dev. Neurosci., 2016, 49, 67-78.
[http://dx.doi.org/10.1016/j.ijdevneu.2015.11.006] [PMID: 26639559]
[4]
Cellot, G.; Maggi, L.; Di Castro, M.A.; Catalano, M.; Migliore, R.; Migliore, M.; Scattoni, M.L.; Calamandrei, G.; Cherubini, E. Premature changes in neuronal excitability account for hippocampal network impairment and autistic-like behavior in neonatal BTBR T+tf/J mice. Sci. Rep., 2016, 6, 31696.
[http://dx.doi.org/10.1038/srep31696] [PMID: 27526668]
[5]
Youssef, M.; Atsak, P.; Cardenas, J.; Kosmidis, S.; Leonardo, E.D.; Dranovsky, A. Early life stress delays hippocampal development and diminishes the adult stem cell pool in mice. Sci. Rep., 2019, 9(1), 4120.
[http://dx.doi.org/10.1038/s41598-019-40868-0] [PMID: 30858462]
[6]
Juruena, M.F.; Eror, F.; Cleare, A.J.; Young, A.H. The Role of Early Life Stress in HPA Axis and Anxiety. InAnxiety Disorders; Springer: Singapore, 2020, pp. 141-153.
[7]
Kambali, M.Y.; Anshu, K.; Kutty, B.M.; Muddashetty, R.S.; Laxmi, T.R. Effect of early maternal separation stress on attention, spatial learning and social interaction behaviour. Exp. Brain Res., 2019, 237(8), 1993-2010.
[http://dx.doi.org/10.1007/s00221-019-05567-2] [PMID: 31154461]
[8]
Sayed Javad Javaheri, E.S.; Bigdeli, M.R.; Zibaii, M.I.; Dargahi, L.; Pouretemad, H.R. Optogenetic stimulation of the anterior cingulate cortex ameliorates autistic-like behaviors in rats induced by neonatal isolation, caudate putamen as a site for alteration. Neuromol. Med., 2019, 21(2), 132-142.
[http://dx.doi.org/10.1007/s12017-019-08526-w] [PMID: 30784006]
[9]
Roque, A.; Ochoa-Zarzosa, A.; Torner, L. Maternal separation activates microglial cells and induces an inflammatory response in the hippocampus of male rat pups, independently of hypothalamic and peripheral cytokine levels. Brain Behav. Immun., 2016, 55, 39-48.
[http://dx.doi.org/10.1016/j.bbi.2015.09.017] [PMID: 26431692]
[10]
Jendželovská, Z.; Jendželovský, R.; Kuchárová, B.; Fedoročko, P. Hypericin in the light and in the dark: Two sides of the same coin. Front. Plant Sci., 2016, 7, 560.
[http://dx.doi.org/10.3389/fpls.2016.00560] [PMID: 27200034]
[11]
Dellafiora, L.; Galaverna, G.; Cruciani, G.; Dall’Asta, C.; Bruni, R. On the mechanism of action of anti-inflammatory activity of hypericin: An in silico study pointing to the relevance of Janus kinases inhibition. Molecules, 2018, 23(12), 3058.
[http://dx.doi.org/10.3390/molecules23123058] [PMID: 30467287]
[12]
Zhang, M.; Wang, Y.; Qian, F.; Li, P.; Xu, X. Hypericin inhibits oligomeric amyloid β42-induced inflammation response in microglia and ameliorates cognitive deficits in an amyloid β injection mouse model of Alzheimer’s disease by suppressing MKL1. Biochem. Biophys. Res. Commun., 2016, 481(1-2), 71-76.
[http://dx.doi.org/10.1016/j.bbrc.2016.11.016] [PMID: 27825966]
[13]
Ennaceur, A.; Delacour, J. A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data. Behav. Brain Res., 1988, 31(1), 47-59.
[http://dx.doi.org/10.1016/0166-4328(88)90157-X] [PMID: 3228475]
[14]
Barbieri, M.; Ossato, A.; Canazza, I.; Trapella, C.; Borelli, A.C.; Beggiato, S.; Rimondo, C.; Serpelloni, G.; Ferraro, L.; Marti, M. Synthetic cannabinoid JWH-018 and its halogenated derivatives JWH-018-Cl and JWH-018-Br impair novel object recognition in mice: Behavioral, electrophysiological and neurochemical evidence. Neuropharmacology, 2016, 109, 254-269.
[http://dx.doi.org/10.1016/j.neuropharm.2016.06.027] [PMID: 27346209]
[15]
Guo, L.; Zhang, Y.; Li, Q. Spectrophotometric determination of dopamine hydrochloride in pharmaceutical, banana, urine and serum samples by potassium ferricyanide-Fe(III). Anal. Sci., 2009, 25(12), 1451-1455.
[http://dx.doi.org/10.2116/analsci.25.1451] [PMID: 20009333]
[16]
Loke, Y.J.; Hannan, A.J.; Craig, J.M. The role of epigenetic change in autism spectrum disorders. Front. Neurol., 2015, 6, 107.
[http://dx.doi.org/10.3389/fneur.2015.00107] [PMID: 26074864]
[17]
Kikusui, T.; Ichikawa, S.; Mori, Y. Maternal deprivation by early weaning increases corticosterone and decreases hippocampal BDNF and neurogenesis in mice. Psychoneuroendocrinology, 2009, 34(5), 762-772.
[http://dx.doi.org/10.1016/j.psyneuen.2008.12.009] [PMID: 19167168]
[18]
Toda, T.; Gage, F.H. Review: Adult neurogenesis contributes to hippocampal plasticity. Cell Tissue Res., 2018, 373(3), 693-709.
[http://dx.doi.org/10.1007/s00441-017-2735-4] [PMID: 29185071]
[19]
Rincel, M.; Darnaudéry, M. Maternal separation in rodents: A journey from gut to brain and nutritional perspectives. Proc. Nutr. Soc., 2020, 79(1), 113-132.
[http://dx.doi.org/10.1017/S0029665119000958] [PMID: 31250784]
[20]
Siniscalco, D.; Schultz, S.; Brigida, A.L.; Antonucci, N. Inflammation and neuro-immune dysregulations in autism spectrum disorders. Pharmaceuticals (Basel), 2018, 11(2), 56.
[http://dx.doi.org/10.3390/ph11020056] [PMID: 29867038]
[21]
Figueiredo, Í.L.; Frota, P.B.; da Cunha, D.G.; da Silva Raposo, R.; Canuto, K.M.; de Andrade, G.M.; Sousa, N.; Moore, S.R.; Anstead, G.M.; Alvarez-Leite, J.I.; Guerrant, R.L.; Oriá, R.B. Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice. Nutrition, 2016, 32(9), 1019-1027.
[http://dx.doi.org/10.1016/j.nut.2016.02.016] [PMID: 27157468]
[22]
Lee, H.J.; Kim, J.W.; Yim, S.V.; Kim, M.J.; Kim, S.A.; Kim, Y.J.; Kim, C.J.; Chung, J.H. Fluoxetine enhances cell proliferation and prevents apoptosis in dentate gyrus of maternally separated rats.Mol. Psychiatry,, 2001.6(6), 610-, 725-728..
[http://dx.doi.org/10.1038/sj.mp.4000954] [PMID: 11673802]
[23]
Kang, B.Y.; Chung, S.W.; Kim, T.S. Inhibition of interleukin-12 production in lipopolysaccharide-activated mouse macrophages by parthenolide, a predominant sesquiterpene lactone in Tanacetum parthenium: Involvement of nuclear factor-kappaB. Immunol. Lett., 2001, 77(3), 159-163.
[http://dx.doi.org/10.1016/S0165-2478(01)00211-5] [PMID: 11410248]
[24]
Couldwell, W.T.; Surnock, A.A.; Tobia, A.J.; Cabana, B.E.; Stillerman, C.B.; Forsyth, P.A.; Appley, A.J.; Spence, A.M.; Hinton, D.R.; Chen, T.C. A phase 1/2 study of orally administered synthetic hypericin for treatment of recurrent malignant gliomas. Cancer, 2011, 117(21), 4905-4915.
[http://dx.doi.org/10.1002/cncr.26123] [PMID: 21456013]
[25]
Wei, H.; Alberts, I.; Li, X. Brain IL-6 and autism. Neuroscience, 2013, 252, 320-325.
[http://dx.doi.org/10.1016/j.neuroscience.2013.08.025] [PMID: 23994594]
[26]
Xie, J.; Huang, L.; Li, X.; Li, H.; Zhou, Y.; Zhu, H.; Pan, T.; Kendrick, K.M.; Xu, W. Immunological cytokine profiling identifies TNF-α as a key molecule dysregulated in autistic children. Oncotarget, 2017, 8(47), 82390-82398.
[http://dx.doi.org/10.18632/oncotarget.19326] [PMID: 29137272]
[27]
Dubey, T; Sahu, G; Kumari, S; Yadav, BS; Sahu, AN Role of herbal drugs on neurotransmitters for treating various CNS disorders:, A review..
[28]
Bork, P.M.; Bacher, S.; Schmitz, M.L.; Kaspers, U.; Heinrich, M. Hypericin as a non-antioxidant inhibitor of NF-κ B. Planta Med., 1999, 65(4), 297-300.
[http://dx.doi.org/10.1055/s-1999-13989] [PMID: 10364831]
[29]
Tusevski, O.; Krstikj, M.; Stanoeva, J.P.; Stefova, M.; Simic, S.G. Phenolic profile and biological activity of Hypericum perforatum L.: Can roots be considered as a new source of natural compounds? S. Afr. J. Bot., 2018, 117, 301-310.
[http://dx.doi.org/10.1016/j.sajb.2018.05.030]
[30]
Valletta, E.; Rinaldi, A.; Marini, M.; Franzese, O.; Roscetti, G. Distinct Hypericum perforatum L. total extracts exert different antitumour activity on erythroleukemic K562 cells. Phytother. Res., 2018, 32(9), 1803-1811.
[http://dx.doi.org/10.1002/ptr.6114] [PMID: 29785769]

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