Abstract
Myristica fragrans, commonly known as nutmeg, belongs to the Myristicaceae family and is used as a spice and for its medicinal properties. The purpose of this study was to assess the neuroprotective effect of M. fragrans seed methanolic extract (MFE) on scopolamine-induced oxidative damage, inflammation, and apoptosis in male rat cortical tissue. MFE or N-acetylcysteine (NAC), a standard antioxidant drug, was administered 7 days before treatment with scopolamine resulted in high levels of malondialdehyde and nitric oxide (oxidative stress biomarkers), tumor necrosis factor-alpha and interleukin-1 beta (inflammatory mediators), and Bax and caspase-3 pro-apoptotic proteins. Additionally, scopolamine significantly depleted levels of glutathione (an antioxidant marker), Bcl-2 and c-FLIP (anti-apoptotic proteins), and antioxidant enzymes activity in cortical tissue. Scopolamine also enhanced acetylcholinesterase activity. MFE treatment protected the cortex of rats from the effects of scopolamine by reversing the effects on these toxicity markers. Interestingly, the neuroprotective effect of MFE was comparable to that exerted by the reference antioxidant NAC. Thus, our findings show that MFE has antioxidant, anti-inflammatory, and anti-apoptotic effects. The beneficial effects of MFE on scopolamine were partially mediated by promoting heme oxygenase 1 (Hmox1) expression and preserving cortical tissue structure.
Similar content being viewed by others
References
Abdel Moneim AE (2013) The neuroprotective effects of purslane (Portulaca oleracea) on rotenone-induced biochemical changes and apoptosis in brain of rat. CNS Neurol Disord drug targets 12(6):830–841. https://doi.org/10.2174/18715273113129990081
Abdel Moneim AE (2015) Oxidant/antioxidant imbalance and the risk of Alzheimer’s disease. Curr Alzheimer Res 12:335–349 doi:CAR-EPUB-66159
Abdel-Rahman Mohamed A, Metwally MM, Khalil SR, Salem GA, Ali HA (2019) Moringa oleifera extract attenuates the CoCl(2) induced hypoxia of rat's brain: expression pattern of HIF-1α. NF-kB, MAO and EPO Biomed pharmacother 109:1688–1697. https://doi.org/10.1016/j.biopha.2018.11.019
Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126
Al Omairi NE, Al-Brakati AY, Kassab RB, Lokman MS, Elmahallawy EK, Amin HK, Abdel Moneim AE (2019) Soursop fruit extract mitigates scopolamine-induced amnesia and oxidative stress via activating cholinergic and Nrf2/HO-1 pathways. Metab Brain Dis 34(3):853–864. https://doi.org/10.1007/s11011-019-00407-2
Almeer RS, Abdel Moneim AE (2018) Evaluation of the protective effect of olive leaf extract on cisplatin-induced testicular damage in rats. Oxid Med Cell Longev 2018:8487248. https://doi.org/10.1155/2018/8487248
Almeer RS, Mahmoud SM, Amin HK, Abdel Moneim AE (2018) Ziziphus spina-christi fruit extract suppresses oxidative stress and p38 MAPK expression in ulcerative colitis in rats via induction of Nrf2 and HO-1 expression. Food Chem Toxicol 115:49–62 doi:S0278–6915(18)30141–8
Al-Megrin WA, Alkhuriji AF, Yousef AOS, Metwally DM, Habotta OA, Kassab RB, Abdel Moneim AE, El-Khadragy MF (2020) Antagonistic efficacy of luteolin against lead acetate exposure-associated with hepatotoxicity is mediated via antioxidant, anti-inflammatory, and anti-apoptotic activities. Antioxidants 9:10. https://doi.org/10.3390/antiox9010010
Andrade S, Ramalho MJ, Loureiro JA, Pereira MDC (2019) Natural compounds for Alzheimer’s disease therapy: a systematic review of preclinical and clinical studies. Int J Mol Sci 20 doi:ijms20092313
Antonio RL et al (2013) Formulas used by Tibetan doctors at Men-Tsee-Khang in India for the treatment of neuropsychiatric disorders and their correlation with pharmacological data. Phytother Res : PTR 27:552–563. https://doi.org/10.1002/ptr.4749
Barnes DE, Yaffe K (2011) The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol 10:819–828 doi:S1474-4422(11)70072-2
Cao GY, Xu W, Yang XW, Gonzalez FJ, Li F (2015) New neolignans from the seeds of Myristica fragrans that inhibit nitric oxide production. Food Chem 173:231–237 doi:S0308–8146(14)01585–4
Champasuri S, Itharat A (2016) Bioactivities of ethanolic extracts of three parts (wood, nutmeg and mace) from Myristica fragrans. Houtt J med Assoc Thai 99(Suppl 4):S124–S130
Croft KD et al (2017) Structural requirements of flavonoids to induce heme oxygenase-1 expression. Free Radical Biol Med 113:165–175. https://doi.org/10.1016/j.freeradbiomed.2017.09.030
Dhingra D, Parle M, Kulkarni SK (2006) Comparative brain cholinesterase-inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic acid, and metrifonate in mice. J Med Food 9:281–283. https://doi.org/10.1089/jmf.2006.9.281
Di Meo S, Reed TT, Venditti P, Victor VM (2016) Role of ROS and RNS sources in physiological and pathological conditions. Oxid Med Cell Longev 2016:1245049. https://doi.org/10.1155/2016/1245049
Dkhil M, Abdel Moneim A, Hafez T, Mubaraki M, Mohamed W, Thagfan F, Al-Quraishy S, (2019) Myristica fragrans Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway. International Journal of Molecular Sciences 20 (4):993
El-Alfy AT, Wilson L, ElSohly MA, Abourashed EA (2009) Towards a better understanding of the psychopharmacology of nutmeg: activities in the mouse tetrad assay. J Ethnopharmacol 126:280–286 doi:S0378-8741(09)00524-8
El-Khadragy MF, Al-Olayan EM, Abdel Moneim AE (2014) Neuroprotective effects of Citrus reticulata in scopolamine-induced dementia oxidative stress in rats. CNS Neurol Disord drug targets 13:684–690 doi:CNSNDDT-EPUB-61028
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77
Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95
Garcia-Huerta P, Troncoso-Escudero P, Jerez C, Hetz C, Vidal RL (2016) The intersection between growth factors, autophagy and ER stress: A new target to treat neurodegenerative diseases? Brain Res 1649 (Pt B):173-180. doi:S0006-8993(16)30128-7
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126:131–138 doi:0003-2697(82)90118-X
Hartl R, Gleinich A, Zimmermann M (2011) Dramatic increase in readthrough acetylcholinesterase in a cellular model of oxidative stress. J Neurochem 116:1088–1096. https://doi.org/10.1111/j.1471-4159.2010.07164.x
Hou JP, Wu H, Wang Y, Weng XC (2012) Isolation of some compounds from nutmeg and their antioxidant activities. Czech J Food Sci 30:164–170
Jahanshahi M, Azami NS, Nickmahzar E (2012) Effect of scopolamine-based amnesia on the number of astrocytes in the rat’s hippocampus. Int J Morphol 30:388–393
Khalil SR, Khalifa HA, Abdel-Motal SM, Mohammed HH, Elewa YHA, Mahmoud HA (2018) Spirulina platensis attenuates the associated neurobehavioral and inflammatory response impairments in rats exposed to lead acetate. Ecotoxicol Environ Saf 157:255–265. https://doi.org/10.1016/j.ecoenv.2018.03.068
Khalil SR, Mohammed WA, Zaglool AW, Elhady WM, Farag MR, El Sayed SAM (2019) Inflammatory and oxidative injury is induced in cardiac and pulmonary tissue following fipronil exposure in Japanese quail: mRNA expression of the genes encoding interleukin 6, nuclear factor kappa B, and tumor necrosis factor-alpha. Environ Pollut 251:564–572. https://doi.org/10.1016/j.envpol.2019.05.012
Kim DO, Chun OK, Kim YJ, Moon HY, Lee CY (2003) Quantification of polyphenolics and their antioxidant capacity in fresh plums. J Agric Food Chem 51:6509–6515. https://doi.org/10.1021/jf0343074
Liu W, Rabinovich A, Nash Y, Frenkel D, Wang Y, Youdim MBH, Weinreb O (2017) Anti-inflammatory and protective effects of MT-031, a novel multitarget MAO-A and AChE/BuChE inhibitor in scopolamine mouse model and inflammatory cells. Neuropharmacology 113:445–456. https://doi.org/10.1016/j.neuropharm.2016.10.028
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Maher P, Hanneken A (2005) Flavonoids protect retinal ganglion cells from oxidative stress-induced death. Invest Ophthalmol Vis Sci 46:4796–4803 doi:46/12/4796
Mahmoud SM, Abdel Moneim AE, Qayed MM, El-Yamany NA (2019) Potential role of N-acetylcysteine on chlorpyrifos-induced neurotoxicity in rats. Environ Sci Pollut Res Int 26:20731–20741. https://doi.org/10.1007/s11356-019-05366-w
Mannervik B (1999) Measurement of glutathione reductase activity. Curr Protoc Toxicol 00:7.2.1–7.2.4. https://doi.org/10.1002/0471140856.tx0702s00
Moniruzzaman M, Chin YW, Cho J (2018) HO-1 dependent antioxidant effects of ethyl acetate fraction from Physalis alkekengi fruit ameliorates scopolamine-induced cognitive impairments. Cell Stress Chaperones 23:763–772. https://doi.org/10.1007/s12192-018-0887-0
Mukherjee PK, Kumar V, Houghton PJ (2007) Screening of Indian medicinal plants for acetylcholinesterase inhibitory activity. Phytother Res PTR 21:1142–1145. https://doi.org/10.1002/ptr.2224
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358
Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169 doi:0022–2143(67)90076–5
Parle M, Dhingra D, Kulkarni SK (2004) Improvement of mouse memory by Myristica fragrans seeds. J Med Food 7:157–161. https://doi.org/10.1089/1096620041224193
Rountree SD, Chan W, Pavlik VN, Darby EJ, Siddiqui S, Doody RS (2009) Persistent treatment with cholinesterase inhibitors and/or memantine slows clinical progression of Alzheimer disease. Alzheimers Res Ther 1 (2):7
Safa AR (2012) c-FLIP, a master anti-apoptotic regulator. Exp Oncol 34:176–184 doi:3429
Saikia B et al (2018) Zanthoxylum alatum ameliorates scopolamine-induced amnesia in rats: behavioral, biochemical, and molecular evidence. Indian J Pharmacol 50:30–38. https://doi.org/10.4103/ijp.IJP_417_17
Shackelford C, Long G, Wolf J, Okerberg C, Herbert R (2002) Qualitative and quantitative analysis of nonneoplastic lesions in toxicology studies. Toxicol Pathol 30:93–96. https://doi.org/10.1080/01926230252824761
Singh SK, Srikrishna S, Castellani RJ, Perry G (2017) Antioxidants in the prevention and treatment of Alzheimer’s disease. In: Al-Gubory KH, Laher I (eds) Nutritional antioxidant therapies: treatments and perspectives. Springer International Publishing, Cham, pp 523–553. https://doi.org/10.1007/978-3-319-67625-8_20
Sun Y, Oberley LW, Li Y, (1988) A simple method for clinical assay of superoxide dismutase.. Clinical Chemistry 34 (3):497-500
Tajuddin AS, Latif A, Qasmi IA, Amin KM (2005) An experimental study of sexual function improving effect of Myristica fragrans Houtt. (nutmeg) BMC Complement Altern Med 5:16 doi:1472–6882-5-16
Tincer G, Mashkaryan V, Bhattarai P, Kizil C (2016) Neural stem/progenitor cells in Alzheimer’s disease. Yale J Biol Med 89:23–35
Tobinick E (2009) Tumour necrosis factor modulation for treatment of Alzheimer’s disease: rationale and current evidence. CNS Drugs 23:713–725
Wahab A, Ul Haq R, Ahmed A, Khan RA, Raza M (2009) Anticonvulsant activities of nutmeg oil of Myristica fragrans. Phytother Res PTR 23:153–158. https://doi.org/10.1002/ptr.2548
Wang WY, Tan MS, Yu JT, Tan L (2015) Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med 3:136. https://doi.org/10.3978/j.issn.2305-5839.2015.03.49
Zhai H, Inoue T, Moriyama M, Esumi T, Mitsumoto Y, Fukuyama Y (2005) Neuroprotective effects of 2,5-diaryl-3,4-dimethyltetrahydrofuran neolignans. Biol Pharm Bull 28:289–293 doi:JST.JSTAGE/bpb/28.289
Zhang CR, Jayashre E, Kumar PS, Nair MG (2015) Antioxidant and antiinflammatory compounds in nutmeg (Myristicafragrans) pericarp as determined by in vitro assays. Nat Prod Commun 10:1399–1402
Acknowledgments
The authors extend appreciations to the Deanship of Scientific Research at King Saud University for funding the work through the research group project number RG-198. The authors would like to thank the Deanship of Scientific Research and RSSU at King Saud University for their technical support.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Responsible editor: Mohamed Abdel-Daim
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Al-Quraishy, S., Dkhil, M.A., Abdel-Gaber, R. et al. Myristica fragrans seed extract reverses scopolamine-induced cortical injury via stimulation of HO-1 expression in male rats. Environ Sci Pollut Res 27, 12395–12404 (2020). https://doi.org/10.1007/s11356-020-07686-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-020-07686-8