FRACTIONS OF ZIZIPHUS JUJUBA HONEY ATTENUATES STREPTOZOTOCIN INDUCED HYPERGLYCEMIA MEDIATED COGNITIVE DYSFUNCTION IN ADULT MICE

Main Article Content

Zaid Ullah
Asad Ullah
Akhtar Muhammad
Shahid Ali Shah

Keywords

Ziziphus Jujuba Honey, STZ, Cognitive dysfunction, Chloroform, ethyl acetate, n-butyl alcohol, TLR4

Abstract

Purpose: There are several evidences showing that hyperglycemic conditions have adverse effects on the brain causing synapse and cognitive deficits along with Alzheimer disease (AD) neuropathology. This study was investigated to examine the neurotherapeutic potential of three different fractions extracted with chloroform (Ch), ethyl acetate (EA) and n-butyl alcohol (n-BuOH) of Ziziphus jujuba Honey against Streptozotocin (STZ) induced hyperglycemia mediated cognitive dysfunction in adult mice.


Methods: Male albino mice were randomly placed into five groups i.e. normal mice, STZ treated (90 mg/kg) mice, STZ+Ch, STZ+EA and STZ+n-BuOH mice (30 mg/kg) for a period of three weeks. Different behavioral tests and biochemical analysis such as Morris water maze test, Y-maze test, GTT, total cholesterol, HDL, LDL, VLDL and TGL were performed to observe the effect of these fractions on memory dysfunction induced by STZ.


Results: A single injection of STZ at a dose of (90 mg/kg) administered intraperitonealy induces hyperglycemia followed by the activation of Toll-like receptor 4 (TLR4 receptors) and ultimately phosphorylated NF-kB (p-NF-kB) activation in the brain of adult albino mice. Moreover, STZ administration significantly caused both pre- and post-synapse loss and cognitive decline in adult albino mice. On the other hand, the administration of three different fractions (Chloroform, Ethyl acetate and n-butyl alcohol) of Ziziphus Jujuba Honey (30 mg/kg daily for three weeks) significantly decreased STZ induced high blood glucose, negatively modulated TLR4 receptors and inhibiting p-NF-kB activation in the brain of adult albino mice.


Conclusion: Taken together, all the results suggest that these three different fractions (Chloroform, Ethyl acetate and N-butyl alcohol) of Ziziphus Jujuba Honey are natural, safe and potent agents against hyperglycemic induced cognitive impairment and associated neurodegenerative diseases.

Abstract 115 | pdf Downloads 42

References

1. Alfaris, N. A., Alshammari, G. M., Altamimi, J. Z., Aljabryn, D. H., Alagal, R. I., Aldera, H., ... & Yahya, M. A. (2021). Ellagic acid prevents streptozotocin-induced hippocampal damage and memory loss in rats by stimulating Nrf2 and nuclear factor-κB, and activating insulin receptor substrate/PI3K/Akt axis. J Physiol Pharmacol, 72(4), 503-515.
2. Barcala Tabarrozzi, A. E., Castro, C. N., Dewey, R. A., Sogayar, M. C., Labriola, L., & Perone, M. J. (2013). Cell-based interventions to halt autoimmunity in type 1 diabetes mellitus. Clinical & Experimental Immunology, 171(2), 135-146.
3. Carroll, W. M., (2019) The global burden of neurological disorders. Lancet Neurol. 18, 418–419. doi: 10.1016/S1474-4422(19)30029-8.
4. Chanput, W., Krueyos, N., & Ritthiruangdej, P. (2016). Anti-oxidative assays as markers for anti-inflammatory activity of flavonoids. International Immunopharmacology, 40, 170-175.
5. Chen, C., Cohrs, C. M., Stertmann, J., Bozsak, R., & Speier, S. (2017). Human beta cell mass and function in diabetes: Recent advances in knowledge and technologies to understand disease pathogenesis. Molecular metabolism, 6(9), 943-957.
6. Chen, H., Lin, H., Xie, S., Huang, B., Qian, Y., Chen, K., ... & Wu, Y. (2019). Myricetin inhibits NLRP3 inflammasome activation via reduction of ROS-dependent ubiquitination of ASC and promotion of ROS-independent NLRP3 ubiquitination. Toxicology and applied pharmacology, 365, 19-29.
7. Eteraf-Oskouei, T., & Najafi, M. (2013). Traditional and modern uses of natural honey in human diseases: a review. Iranian journal of basic medical sciences, 16(6), 731.
8. Grossman, R. The Other Medicines: The Penicillin of Bees. Pan Books; London, UK: 1986. p. 177.
9. Hamdy, A. A., Ismail, H. M., Ael-M, A. A., & Gomaa, N. F. (2009). Determination of flavonoid and phenolic Acid contents of clover, cotton and citrus floral honeys. The Journal of the Egyptian Public Health Association, 84(3-4), 245-259.
10. Kandeda, A. K., Taiwe, G. S., Moto, F. C., Ngoupaye, G. T., Nkantchoua, G. C., Njapdounke, J. S., ... & Ngo Bum, E. (2017). Antiepileptogenic and neuroprotective effects of Pergularia daemia on pilocarpine model of epilepsy. Frontiers in Pharmacology, 8, 440.
11. Kraeuter, A. K., Guest, P. C., & Sarnyai, Z. (2019). The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice. Methods in molecular biology (Clifton, N.J.), 1916, 105–111. https://doi.org/10.1007/978-1-4939-8994-2_10
12. Liu, L. P., Yan, T. H., Jiang, L. Y., Hu, W., Hu, M., Wang, C., ... & Hong, H. (2013). Pioglitazone ameliorates memory deficits in streptozotocin-induced diabetic mice by reducing brain β-amyloid through PPARγ activation. Acta Pharmacologica Sinica, 34(4), 455-463.
13. Mahmood, T., & Yang, P. C. (2012). Western blot: technique, theory, and trouble shooting. North American journal of medical sciences, 4(9), 429–434. https://doi.org/10.4103/1947-2714.100998
14. Misra, F., Fridovish, I., (1972) Determination of the level of superoxide dismutase in whole blood. Yale University Press New Haven. 101, p. 109.
15. Ramezani Ramezani, M., Darbandi, N., Khodagholi, F., & Hashemi, A. (2016). Myricetin protects hippocampal CA3 pyramidal neurons and improves learning and memory impairments in rats with Alzheimer's disease. Neural regeneration research, 11(12), 1976. doi: 10.4103/1673-5374.197141.
16. Salim, S., (2017) Oxidative Stress and the Central Nervous System. J. Pharmacol. Exp. Ther. 360, 201–205.
17. Smith, C. V., & Anderson, R. E. (1987). Methods for determination of lipid peroxidation in biological samples. Free Radical Biology and Medicine, 3(5), 341-344.
18. Tsikas, D. (2007). Analysis of nitrite and nitrate in biological fluids by assays based on the Griess reaction: appraisal of the Griess reaction in the L-arginine/nitric oxide area of research. Journal of Chromatography B, 851(1-2), 51-70.
19. Wang, B., Zhong, Y., Gao, C., & Li, J. (2017). Myricetin ameliorates scopolamine-induced memory impairment in mice via inhibiting acetylcholinesterase and down-regulating brain iron. Biochemical and Biophysical Research Communications, 490(2), 336-342.
20. White, J.W. Jr. (1957b) The composition of honey. Bee World. 80, 386–392.
21. White, J.W. Jr. Hoban, N. (1957a) Composition of honey. IV. Identification of the disaccharides. Arch. Biochem. Biophys. 80, 386–392.
22. Wilson, J. I., George, B. O., & Umukoro, G. E. (2011). Effects of honey on the histology of liver in adult Wistar rats. Biology and Medicine, 3(1), 1-5.
23. Wootton, M., Edwards, R. A., Faraji-Haremi, R., & Williams, P. J. (1978). Effect of accelerated storage conditions on the chemical composition and properties of Australian honeys 3. Changes in volatile components. Journal of apicultural Research, 17(3), 167-172.
24. Zaia, D. A. M., Marques, F. R., & Zaia, C. T. B. V. (2005). Spectrophotometric determination of total proteins in blood plasma: a comparative study among dye-binding methods. Brazilian archives of biology and technology, 48, 385-388.

Most read articles by the same author(s)