Effect of standardized Eucalyptus globulus leaf extract on brain oxidative stress and aberrant neurochemistry of fructose-streptozotocin-induced diabetic rats

Authors

  • A. C. Akinmoladun
  • Bidemi Sikirat Jiddah Kazeem
  • Morenikejimi Bello
  • Professor

DOI:

https://doi.org/10.54548/njps.v38i1.10

Abstract

The neuro-pharmacological effect of Eucalyptus globulus ethanol leaf extract in fructose-streptozotocin-induced diabetic rats was evaluated in this study. The phytochemical analysis of the extract was carried out using HPLC-DAD. Diabetes was induced in rats with 10% fructose in drinking water and a single intraperitoneal injection of 40 mg/kg streptozotocin (STZ). Diabetic animals were orally treated with 100-400 mg/kg of the extract for 21 days with glibenclamide as the reference drug. Blood and brain tissue were processed for the determination of serum electrolyte levels, hematological indices, and biochemical estimations. Ergosterol, pinitol, catechin, quercetin, robinetinidol, and other polyphenols were identified in the extract. Diabetic animals showed decreased serum potassium and sodium ion levels and decreased hematocrit, hemoglobin, red blood cells, white blood cells and lymphocytes but increased neutrophils. The brains of animals in the untreated diabetic group with increased blood glucose level showed oxidative stress (increased level of MDA and myeloperoxidase but decreased level of reduced glutathione and superoxide dismutase) and disturbed neurochemistry (increased level of acetylcholinesterase and monoamine oxidase but decreased level of Na+K+ATPase, tyrosine hydroxylase and dopamine). Administration of the Eucalyptus globulus leaf extract remarkably ameliorated the observed hyperglycemia, electrolyte, and hematological imbalances in animals. In addition, the administration of the extract attenuated the brain redox imbalance, and neurochemical disturbances in the rats. These results show that Eucalyptus globulus leaves contain antioxidant and neurotransmitter modulating phytochemicals with the potential to be developed as therapeutic agents for the management of diabetic cerebrovascular problems and related complications.

References

Adedara, I. A., Fasina, O. B., Ayeni, M. F., Ajayi, O. M. and Farombi, E. O. (2019). Protocatechuic acid ameliorates neurobehavioral deficits via suppression of oxidative damage, inflammation, caspase-3 and acetylcholinesterase activities in diabetic rats. Food and Chemical Toxicology 125: 170–181. https://doi.org/10.1016/j.fct.2018.12.040

Adedara, I. A., Okpara, E. S., Busari, E. O., Omole, O., Owumi, S. E. and Farombi, E. O. (2019). Dietary protocatechuic acid abrogates male reproductive dysfunction in streptozotocin-induced diabetic rats via suppression of oxidative damage, inflammation and caspase-3 activity. European Journal of Pharmacology 849: 30–42. https://doi.org/10.1016/j.ejphar.2019.01.033

Akin, M., Aktumsek, A. and Nostro, A. (2012). Antibacterial activity and composition of the essential oils of Eucalyptus camaldulensis Dehn. And Myrtus communis L. growing in Northern Cyprus. African Journal of Biotechnology 9(4): 531–535. https://doi.org/10.4314/ajb.v9i4.

Barbieri, J., Fontela, P. C., Winkelmann, E. R., Zimmermann, C. E. P., Sandri, Y. P., Mallet, E. K. V. and Frizzo, M. N. (2015). Anemia in Patients with Type 2 Diabetes Mellitus. Anemia 2015. https://doi.org/10.1155/2015/354737

Beutler, E., Duron, O. and Kelly, B. M. (1963). Improved method for the determination of blood glutathione. The Journal of Laboratory and Clinical Medicine 61: 882–888.

Bule, M., Abdurahman, A., Nikfar, S., Abdollahi, M. and Amini, M. (2019). Antidiabetic effect of quercetin: A systematic review and meta-analysis of animal studies. Food and Chemical Toxicology 125: 494–502. https://doi.org/10.1016/j.fct.2019.01.037

Cheruku, S. P., Ramalingayya, G. V., Chamallamudi, M. R., Biswas, S., Nandakumar, K., Nampoothiri, M., Gourishetti, K. and Kumar, N. (2018). Catechin ameliorates doxorubicin-induced neuronal cytotoxicity in in vitro and episodic memory deficit in in vivo in Wistar rats. Cytotechnology 70(1): 245–259. https://doi.org/10.1007/S10616-017-0138-8

Damjanović-Vratnica, B., Đakov, T., Šuković, D. and Damjanović, J. (2011). Antimicrobial Effect of Essential Oil Isolated from Eucalyptus globulus Labill. From Montenegro. Czech J. Food Sci 29(3), 277–284.

Eiserich, J. P., Hristova, M., Cross, C. E., Jones, A. D., Freeman, B. A., Halliwell, B. and van der Vliet, A. (1998). Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature 391(6665): 393–397. https://doi.org/10.1038/34923

Ellman, G. L., Courtney, K. D., Andres, V. and Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology 7(2): 88–95. https://doi.org/10.1016/0006-2952(61)90145-9

Fasil, A., Biadgo, B. and Abebe, M. (2018). Glycemic control and diabetes complications among diabetes mellitus patients attending at University of Gondar Hospital, Northwest Ethiopia. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 12: 75–83. https://doi.org/10.2147/DMSO.S185614

Geethan, P. K. M. A. and Prince, P. S. M. (2008). Antihyperlipidemic effect of D-pinitol on streptozotocin-induced diabetic Wistar rats. Journal of Biochemical and Molecular Toxicology 22(4): 220–224. https://doi.org/10.1002/JBT.20218

Gray, A. M. and Flatt, P. R. (1998). Antihyperglycemic Actions of Eucalyptus globulus (Eucalyptus) are Associated with Pancreatic and Extra-Pancreatic Effects in Mice. The Journal of Nutrition 128(12): 2319–2323. https://doi.org/10.1093/JN/128.12.2319

Güemes, A. and Georgiou, P. (2018). Review of the role of the nervous system in glucose homoeostasis and future perspectives towards the management of diabetes. Bioelectronic Medicine 4(1). https://doi.org/10.1186/S42234-018-0009-4

Guo, L., Zhang, Y. and Li, Q. (2009). Spectrophotometric determination of dopamine hydrochloride in pharmaceutical, banana, urine and serum samples by potassium ferricyanide-Fe(III). Analytical Sciences 25(12): 1451–1455. https://doi.org/10.2116/analsci.25.1451

Hamed, S. A. (2017). Brain injury with diabetes mellitus: Evidence, mechanisms and treatment implications. Expert Review of Clinical Pharmacology 10(4): 409–428. https://doi.org/10.1080/17512433.2017.1293521

Hare, G. M. T. (2004). Anaemia and the brain. Current Opinion in Anaesthesiology 17(5), 363–369. https://doi.org/10.1097/00001503-200410000-00003

Holt, A., Sharman, D. F., Baker, G. B. and Palcic, M. M. (1997). A Continuous Spectrophotometric Assay for Monoamine Oxidase and Related Enzymes in Tissue Homogenates. Analytical Biochemistry 244(2): 384–392. https://doi.org/10.1006/ABIO.1996.9911

IDF. (2019). IDF Diabetes Atlas (19th ed.). International Diabetes Federation.

Jiang, Z., Zhang, J., Cai, Y., Huang, J. and You, L. (2017). Catechin attenuates traumatic brain injury-induced blood-brain barrier damage and improves longer-term neurological outcomes in rats. Experimental Physiology 102(10): 1269–1277. https://doi.org/10.1113/EP086520

Khanduker, S., Ahmed, R., Khondker, F., Aharama, A., Afrose, N. and Chowdhury, M. (2017). Electrolyte Disturbances in Patients with Diabetes Mellitus. Bangladesh Journal of Medical Biochemistry 10(1): 27–35. https://doi.org/10.3329/BJMB.V10I1.36698

Li, H. F., Cai, L. and Golden, A. R. (2019). Short-Term Trends in Economic Burden and Catastrophic Costs of Type 2 Diabetes Mellitus in Rural Southwest China. Journal of Diabetes Research 2019. https://doi.org/10.1155/2019/9626413

Maciel, R. M., Carvalho, F. B., Olabiyi, A. A., Schmatz, R., Gutierres, J. M., Stefanello, N., Zanini, D., Rosa, M. M., Andrade, C. M., Rubin, M. A., Schetinger, M. R., Morsch, V. M., Danesi, C. C. and Lopes, S. T. A. (2016). Neuroprotective effects of quercetin on memory and anxiogenic-like behavior in diabetic rats: Role of ectonucleotidases and acetylcholinesterase activities. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 84: 559–568. https://doi.org/10.1016/J.BIOPHA.2016.09.069

Misra, H. P. and Fridovich, I. (1972). The Role of Superoxide Anion in the Autoxidation of Epinephrine and a Simple Assay for Superoxide Dismutase. Journal of Biological Chemistry 247(10) 317–3175.

Mrabti, H. N., Jaradat, N., Fichtali, I., Ouedrhiri, W., Jodeh, S., Ayesh, S., Cherrah, Y. and Faouzi, M. E. A. (2018). Separation, Identification, and Antidiabetic Activity of Catechin Isolated from Arbutus unedo L. Plant Roots. Plants 7(2): 31. https://doi.org/10.3390/PLANTS7020031

Obafemi, T. O., Akinmoladun, A. C., Olaleye, M. T., Agboade, S. O. and Onasanya, A. A. (2017). Antidiabetic potential of methanolic and flavonoid-rich leaf extracts of Synsepalum dulcificum in type 2 diabetic rats. Journal of Ayurveda and Integrative Medicine 8(4). https://doi.org/10.1016/j.jaim.2017.01.008

Obafemi, T. O., Olaleye, M. T. and Akinmoladun, A. C. (2019). Antidiabetic property of miracle fruit plant (Synsepalum dulcificum Shumach. & Thonn. Daniell) leaf extracts in fructose-fed streptozotocin-injected rats via anti-inflammatory activity and inhibition of carbohydrate metabolizing enzymes. Journal of Ethnopharmacology, 244: 112124. https://doi.org/10.1016/j.jep.2019.112124

Ojo, O. B., Amoo, Z. A., Saliu, I. O., Olaleye, M. T., Farombi, E. O. and Akinmoladun, A. C. (2019). Neurotherapeutic potential of kolaviron on neurotransmitter dysregulation, excitotoxicity, mitochondrial electron transport chain dysfunction and redox imbalance in 2-VO brain ischemia/reperfusion injury. Biomedicine and Pharmacotherapy 111: 859–872. https://doi.org/10.1016/j.biopha.2018.12.144

Parashar, A., Mehta, V. and Malairaman, U. (2018). Type 2 Diabetes Mellitus Is Associated with Social Recognition Memory Deficit and Altered Dopaminergic Neurotransmission in the Amygdala. Annals of Neurosciences 24(4): 212–220. https://doi.org/10.1159/000479637

Podestà, M. A., Faravelli, I., Cucchiari, D., Reggiani, F., Oldani, S., Fedeli, C. and Graziani, G. (2015). Neurological counterparts of hyponatremia: Pathological mechanisms and clinical manifestations. Current Neurology and Neuroscience Reports 15(4): 1–10. https://doi.org/10.1007/S11910-015-0536-2

Pop-Busui, R., Boulton, A. J. M., Feldman, E. L., Bril, V., Freeman, R., Malik, R. A., Sosenko, J. M. and Ziegler, D. (2017). Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care 40(1): 136. https://doi.org/10.2337/DC16-2042

Prabhakar, V., Gupta, D., Kanade, P. and Radhakrishnan, M. (2015). Diabetes-associated depression: The serotonergic system as a novel multifunctional target. Indian Journal of Pharmacology 47(1): 4. https://doi.org/10.4103/0253-7613.150305

Rajput, M. S. and Sarkar, P. D. (2017). Modulation of neuro-inflammatory condition, acetylcholinesterase and antioxidant levels by genistein attenuates diabetes associated cognitive decline in mice. Chemico-Biological Interactions 268: 93–102. https://doi.org/10.1016/J.CBI.2017.02.021

Rengarajan, T., Rajendran, P., Nandakumar, N., Lokeshkumar, B. and Balasubramanian, M. P. (2015). D-Pinitol Protects Against Carbon Tetrachloride-Induced Hepatotoxicity in Rats. Journal of Environmental Pathology, Toxicology and Oncology 34(4): 287–298. https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2015013837

Shiman, R., Akino, M. and Kaufman, S. (1971). Solubilization and partial purification of tyrosine hydroxylase from bovine adrenal medulla. The Journal of Biological Chemistry 246(5): 1330–1340.

Svoboda, P. and Mosinger, B. (1981). Catecholamines and the brain microsomal Na, K-adenosinetriphosphatase—I. Protection against lipoperoxidative damage. Biochemical Pharmacology 30(5): 427–432. https://doi.org/10.1016/0006-2952(81)90626-2

Varshney, R. and Kale, R. K. (1990). Effects of calmodulin antagonists on radiation-induced lipid peroxidation in microsomes. International Journal of Radiation Biology 58(5): 733–743. https://doi.org/10.1080/09553009014552121

Waikar, S. S., Mount, D. B. and Curhan, G. C. (2009). Mortality after hospitalization with mild, moderate, and severe hyponatremia. The American Journal of Medicine 122(9): 857–865. https://doi.org/10.1016/J.AMJMED.2009.01.027

Witter, A. R., Okunnu, B. M. and Berg, R. E. (2016). The Essential Role of Neutrophils During Infection with the Intracellular Bacterial Pathogen Listeria monocytogenes. Journal of Immunology 197(5): 1557. https://doi.org/10.4049/JIMMUNOL.1600599

Zatterale, F., Longo, M., Naderi, J., Raciti, G. A., Desiderio, A., Miele, C. and Beguinot, F. (2020). Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes. Frontiers in Physiology 10. https://doi.org/10.3389/FPHYS.2019.01607

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2023-06-30

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How to Cite

Effect of standardized Eucalyptus globulus leaf extract on brain oxidative stress and aberrant neurochemistry of fructose-streptozotocin-induced diabetic rats. (2023). Nigerian Journal of Physiological Sciences, 38(1), 65-72. https://doi.org/10.54548/njps.v38i1.10

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