Effects of Sub-acute Administration of Onion Waste Quercetin on the Hippocampus of Mice: A Histological Approach

Abstract

Quercetin is a flavonoid with a great capability of crossing the blood-brain barrier. It is reported to exert numerous beneficial effects on both animal and human health. The study evaluates the effects of onion waste quercetin (OWQ) on the histology of the hippocampus and dentate gyrus of mice. Twenty mice were assigned into four groups (n=5). The groups were given distilled water, and OWQ at 95mg/kg, 190mg/kg, and 380mg/kg respectively for 28 days. The brain of each mouse was harvested afterwards, weighed, and processed for light microscopy. The normal and degenerating cells of the dentate gyrus and hippocampus Cornu Ammonis (CA1 & CA3) were counted. The micrographs of the dentate gyrus showed normal molecular, granular, and polymorphic layers in the control mice, as well as the mice, treated with OWQ with few degenerating cells in the granular layer of OWQ-treated (190mg/kg) mice. The CA3 area of the hippocampus showed normal molecular and polymorphic layers in OWQ-treated mice. However, the granular layer of the mice that received OWQ at 190mg/kg showed numerous degenerating cells. OWQ especially at 95mg/kg was found to significantly increase the number of normal cells of the dentate gyrus and hippocampus (CA1 & CA3) of the brain related to the control at P< .05. It also significantly decreased degenerating cells relative to the control (P< .05). Conclusively, OWQ was found to significantly reduced degenerating cells in the dentate gyrus and hippocampus. Nevertheless, further studies are required to evaluate the possible biochemical mechanisms for this histological event.

Keywords

• Brain
• Degeneration
• Hippocampus
• Onion
• Quercetin

References

1. [1] Sharma, K., Verma, R., Kumar, D., Nepovimova, E., Kuča, K., Kumar, A., Puri, S., “Ethnomedicinal plants used for the treatment of neurodegenerative diseases in Himachal Pradesh, India in Western Himalaya”, Journal of Ethnopharmacology, 293: 115318, (2022).
2. [2] Solanki, I., Parihar, P., Mansuri, M., L., Parihar, M., S., “Flavonoid-based therapies in the early management of neurodegenerative diseases”, Advances in Nutrition, 6(1): 64-72, (2015).
3. [3] Rahmani, M., Álvarez, S., E., N., Hernández, E., B., “The potential use of tetracyclines in neurodegenerative diseases and the role of nano-based drug delivery systems”, European Journal of Pharmaceutical Sciences, 106237, (2022).
4. [4] Wahid, M., Ali, A., Saqib, F., Aleem, A., Bibi, S., Afzal, K., Ali, A., Baig, A., Khan, S., A., Bin Asad, M., H., “Pharmacological exploration of traditional plants for the treatment of neurodegenerative disorders”, Phytotherapy Research, 34: 3089-3112, (2020).
5. [5] Hassan, T., Saeed, S., Hassan, M., Naseem, S., Siddique, S., “Ethnomedicinal plants in the treatment of neurodegenerative diseases: a narrative”, Gomal Journal of Medical Sciences, 19: 35-44, (2021).
6. [6] Ratheesh, G., Tian, L., Venugopal, J., R., Ezhilarasu, H., Sadiq, A., Fan, T., P., Ramakrishna, S., “Role of medicinal plants in neurodegenerative diseases” Biomanufacturing Reviews, 2: 1-16, (2017).
7. [7] Costa, L., G., Garrick, J., M., Roquè, P., J., Pellacani, C., “Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More” Oxidative Medicine and Cellular Longevity, 2016: 2986796, (2016).
8. [8] Salehi, B., Machin, L., Monzote, L., Sharifi-Rad, J., Ezzat, S., M., Salem, M., A., Merghany, R., M., El Mahdy, N., M., Kılıc, C., Ş., Sytar, O., Sharifi-Rad, M., Sharopov, F., Martins, N., Martorell, M., Cho, W., C., “Therapeutic Potential of Quercetin: New Insights and Perspectives for Human Health”, ACS Omega, 5: 11849-11872, (2020).

9. [9] Sytar, O., Bruckova, K., Hunkova, E., Zivcak, M., Konate, K., Brestic, M., “The application of multiplex fluorimetric sensor for analysis flavonoids content in the medical herbs family Asteraceae, Lamiaceae, Rosaceae”, Biological Research, 48: 5, (2015).
10. [10] Devore, E., E, Kang, J., H., Breteler, M., Grodstein, F., “Dietary intakes of berries and flavonoids in relation to cognitive decline”, Annals of Neurology, 72: 135-143 (2012).
11. [11] Kawabata, K., Mukai, R., Ishisaka, A., “Quercetin and related polyphenols: New insights and implications for their bioactivity and bioavailability”, Food Function, 6: 1399-1417, (2015).
12. [12] Xiao, L., Luo, G., Tang, Y., Yao, P., “Quercetin and iron metabolism: what we know and what we need to know,” Food and Chemical Toxicology, 114: 190-203, (2018).
13. [13] El-Horany, H., E., El-Latif, R., N., A., ElBatsh, M., M., Emam, M., N., “Ameliorative effect of quercetin on neurochemical and behavioural deficits in rotenone rat model of Parkinson’s disease: Modulating autophagy (quercetin on experimental Parkinson’s disease)”, Journal of Biochemistry and Molecular Toxicology, 30: 360-369, (2016).
14. [14] Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M., T., Wang, S., Liu, H., Yin, Y., “Quercetin, Inflammation and Immunity”, Nutrients, 8: 167, (2016).
15. [15] Khan, H., Ullah, H., Aschner, M., Cheang, W., S., Akkol, E., K., “Neuroprotective Effects of Quercetin in Alzheimer’s Disease”, Biomolecules, 10: 59, (2020).
16. [16] Ullah, H., Khan, H., “Anti-Parkinson potential of silymarin: Mechanistic insight and therapeutic standing”, Frontiers in Pharmacology, 9: 422, (2018).
17. [17] Madiha, S., Batool, Z., Tabassum, S., Liaquat, L., Sadir, S., Shahzad, S., Naqvi, F., Saleem, S., Yousuf, S., Nawaz, A., Ahmad, S., Sajid, I., Afzal, A., Haider, S., “Quercetin exhibits potent antioxidant activity, restores motor and non-motor deficits induced by rotenone toxicity”, PLoS ONE, 16(11): e0258928, (2021).
18. [18] Shen, P., Lin, W., Deng, X., Ba, X., Han, L., Chen, Z., Qin, K., Huang, Y., Tu, S., “Potential Implications of Quercetin in Autoimmune Diseases”, Frontiers in Immunology, 12: 689044, (2021).
19. [19] Dibal, N., I., Garba, S., H., Jacks, T., W., “Onion Peel Quercetin Attenuates Ethanol Induced Liver Injury in Mice by Preventing Oxidative Stress and Steatosis”, Biomedical Research and Therapy, 9(6): 5101-5111, (2022).
20. [20] Mehany, A., B., M., Belal, A., Santali, E., Y., Shaaban, S., Abourehab, M., A., S., El-Feky, O., A., Diab, M., Abou Galala, F., M., A., Elkaeed, E., B., Abdelhamid, G., “Biological Effect of Quercetin in Repairing Brain Damage and Cerebral Changes in Rats: Molecular Docking and In Vivo Studies,” BioMed Research International, 2022: 8962149, (2022).
21. [21] Chorolque, A., Pellejero, G., Sosa, M., C., Palacios, J., Aschkar, G., Garcia‑Delgado, C., Jimenez‑Ballesta, R., “Biological control of soil‑borne phytopathogenic fungi through onion waste composting: implications for circular economy perspective”, International Journal of Environmental Science and Technology, 19: 6411-6420, (2022).
22. [22] Pellejero, G., Rodriguez, K., Ashchka, G., Vela, E., Garcia-Delgado, C., Jimenez-Ballesta, R., “Onion waste recycling by vermicomposting: nutrients recovery and agronomical assessment”, International Journal of Environmental Science and Technology, 17: 3289-3296, (2020).
23. [23] Dibal, N., I., Garba, S., H., Jacks, T., W., “Repeated 28-day oral dose toxicity of onion skin quercetin in mice”, Comparative Clinical Pathology, 29(6): 1219-1227, (2020).
24. [24] Saraste, A., “Morphologic Criteria and Detection of Apoptosis”, Herz, 24: 189-195, (1999).
25. [25] Mesram, N., Nagapuri, K., Banala, R., R., Nalagoni, C., R., Karnati, P., R., “Quercetin treatment against NaF induced oxidative stress-related neuronal and learning changes in developing rats”, Journal of King Saud University of Sciences, 29: 221-229, (2017).
26. [26] Bhimanwar, A., A., Ghaisas, M., M., Shete, R., V., “Silymarin, Quercetin and Hesperidin Combination Ameliorates Learning and Memory Deficit in 3 Nitro Propionic Acid-Induced Rat Model of Huntington’s Disease”, International Journal of Pharmaceutical Investigation, 12(3): 363-369, (2022).
27. [27] Dora, M., Taha, N., Lebda, M., Hashem, A., Elfeky, M., “Effect of iron oxide nanoparticles and quercetin on rat body weight and brain iron content”, Damanhour Journal of Veterinary Sciences, 5(2): 1-5, (2021).
28. [28] Bagad, M., Khan, Z., A., “Poly(n-butyl cyanoacrylate) nanoparticles for oral delivery of quercetin: Preparation, characterization, and pharmacokinetics and biodistribution studies in Wistar rats”, International Journal of Nanomedicine, 10: 3921-3935, (2015).
29. [29] Najafabadi, R., E., Kazemipour, N., Esmaeili, A., Beheshti, S., Nazifi, S., “Using superparamagnetic iron oxide nanoparticles to enhance the bioavailability of quercetin in the intact rat brain”, BMC Pharmacology and Toxicology, 19: 59, (2018).
30. [30] Kumar, P., Sharma, G., Kumar, R., Singh, B., Malik, R., Katare, O., P., Raza, K., “Promises of a biocompatible nanocarrier in improved brain delivery of quercetin: Biochemical, pharmacokinetic and biodistribution evidence”, International Journal of Pharmacy, 515: 307-314, (2016).
31. [31] Qi, Y., Guo, L., Jiang, Y., Shi, Y., Sui, H., Zhao, L., “Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles”, Drug Delivery, 27: 74, (2020).
32. [32] Lee, S-H., Chen, Y-H., Chien, C-C., Yan, Y-H., Chen, H-C., Chuang, H-C., Hsieh, H-I., Cho, K-H., Kuo, L-W., Chou, CC-K., Chiu, M-J., Tee, BL., Chen, T-F., Cheng, T-J., “Three-month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer’s disease mouse model”, PLoS ONE, 16(8): e0254587, (2021).
33. [33] Bano, D., Zanetti, F., Mende, Y., Nicotera, P., “Neurodegenerative processes in Huntington’s disease”, Cell Death and Disease, 2: e228, (2011).
34. [34] Zeng, X-S., Geng, W-S., Jia, J-J., Chen, L., Zhang, P-P., “Cellular and Molecular Basis of Neurodegeneration in Parkinson Disease”, Frontiers in Aging Neuroscience, 10: 109, (2018).
35. [35] Miranda, H., V., Gomes, M., A., Branco-Santos, J., Breda, C., Lázaro, D., F., Lopes, L., V., Herrera, F., Giorgini, F., Outeiro, T., F., “Glycation potentiates neurodegeneration in models of Huntington’s disease”, Scientific Reports, 6: 36798, (2016).
36. [36] Al-Zharani, M., Mubarak, M., Rudayni, H.A., Al-Doaiss A.A., Abd-Elwahab M.M., Al-Eissa, M.S., Quercetin as a Dietary Supplementary Flavonoid Alleviates the Oxidative Stress Induced by lead Toxicity in male Wistar Rats. Nutrients, 15: 1888, (2023).
37. [37] Singh, S., Jamwal, S., Kumar, P., “Neuroprotective potential of Quercetin in combination with piperine against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity”, Neural Regeneration Research, 12(7): 1137-1144, (2017).
38. [38] Kanter, M., Aktas, C., Erboga, M., “Protective effects of quercetin against apoptosis and oxidative stress in streptozotocin-induced diabetic rat testis”, Food and Chemical Toxicology, 50(3-4): 719-725, (2012).