Neuroprotective effects of rosemary extract on white matter of prefrontal cortex in old rats

Document Type : Short Communication


1 Anatomy Department, Faculty of Medicine, Qom University of Medical Sciences, Qom, Iran

2 Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran

3 Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

5 Tissue Engineering and Applied Cell Sciences Department, Faculty of Medicine, Qom University of Medical Sciences, Qom, Iran


Objective(s): During aging, cerebral structures undergo changes due to oxidative stress. The consumption of some plants seems to improve neurological health. For example, rosemary extract (RE) which is widely used as a flavoring food has anti-inflammatory and anti-oxidant activities. Therefore, we aimed to study the effect of RE on the changes related to the aging process in the prefrontal cortex (PFC).
Materials and Methods: Twenty-four male Wistar rats including young and old were purchased. Each group was divided into two subgroups: vehicle and rosemary (old vehicle (OV), old rosemary (OR), young vehicle (YV), and young rosemary (YR) groups). Then, we examined the number of intact neurons, myelin base protein (MBP), white matter (WM), levels of malondialdehyde (MDA), and glutathione peroxidase (GPx) in the PFC. 
Results: The results showed that in the old vehicle rats compared to the young group without treatment, except for the MDA level (which increased), other variables significantly decreased (P≤0.05). Additionally, RE consumption demonstrated a significant elevation of WMA, MBP intensity, number of intact neurons, and GPx activity level, while MDA levels significantly reduced in the treated old rats compared to the old vehicle group (P≤0.05). However, there was no significant difference between the OR and YV groups (P≥0.05). 
Conclusion: Overall, it seems that RE can protect and improve aging damages in the PFC due to its anti-oxidant properties. So, the use of RE can be a suitable strategy to prevent aging complications in the brain. 


Main Subjects

1. Rodríguez-Rodero S, Fernández-Morera JL, Menéndez-Torre E, Calvanese V, Fernández AF, Fraga MF. Aging genetics and aging. Aging Dis  2011; 2:186–195.
2. Lockhart SN, DeCarli C. Structural imaging measures of brain aging. Neuropsychol Rev 2014; 24:271-289.
3. Fjell AM, McEvoy L, Holland D, Dale AM, Walhovd KB, Initiative AsDN. Brain changes in older adults at very low risk for Alzheimer’s disease. J Neurosci 2013; 33:8237-8242.
4. Cefalu CA. Theories and mechanisms of aging. Clin Geriat Med 2011; 27:491-506.
5. Harman D. Origin and evolution of the free radical theory of aging: A brief personal history, 1954–2009. Biogerontology 2009; 10:773-781.
6. Poljšak B, Fink R. The protective role of anti-oxidants in the defence against ROS/RNS-mediated environmental pollution. Oxid Med Cell Longev 2014; 2014: 671539.
7. Posadas S, Caz V, Largo C, De la Gandara B, Matallanas B, Reglero G, et al. Protective effect of supercritical fluid rosemary extract, Rosmarinus officinalis, on anti-oxidants of major organs of aged rats. Exp Gerontol 2009; 44:383-389.
8. Kelsey NA, Wilkins HM, Linseman DA. Nutraceutical anti-oxidants as novel neuroprotective agents. Molecules 2010; 15:7792-7814.
9. Abd El-Ghany MA, Motawee M. Biological effects of yoghurt with rosemary on injured liver rats. Aust J Basic Appl Sci 2012; 6: 525-532.
10. Ojeda-Sana AM, van Baren CM, Elechosa MA, Juárez MA, Moreno S. New insights into antibacterial and anti-oxidant activities of rosemary essential oils and their main components. Food Control 2013; 31:189-195.
11. Doolaege EH, Vossen E, Raes K, De Meulenaer B, Verhé R, Paelinck H, et al. Effect of rosemary extract dose on lipid oxidation, colour stability and anti-oxidant concentrations, in reduced nitrite liver pâtés. Meat Sci 2012; 90:925-931.
12. Rahbardar MG, Hosseinzadeh H. Therapeutic effects of rosemary (Rosmarinus officinalis L.) and its active constituents on nervous system disorders. Iran J Basic Med Sci 2020; 23:1100.
13. Ozarowski M, Mikolajczak PL, Bogacz A, Gryszczynska A, Kujawska M, Jodynis-Liebert J, et al. Rosmarinus officinalis L. leaf extract improves memory impairment and affects acetylcholinesterase and butyrylcholinesterase activities in rat brain. Fitoterapia 2013; 91:261-271.
14. Lipton SA, Rezaie T, Nutter A, Lopez KM, Parker J, Kosaka K, et al. Therapeutic advantage of pro-electrophilic drugs to activate the Nrf2/ARE pathway in Alzheimer’s disease models. Cell Death Dis 2016; 7:2499-2499.
15. Simioni C, Zauli G, Martelli AM, Vitale M, Sacchetti G, Gonelli A, et al. Oxidative stress: role of physical exercise and anti-oxidant nutraceuticals in adulthood and aging. Oncotarget 2018; 9:17181.
16. Rasoolijazi H, Mehdizadeh M, Soleimani M, Nikbakhte F, Farsani ME, Ababzadeh S. The effect of rosemary extract on spatial memory, learning and anti-oxidant enzymes activities in the hippocampus of middle-aged rats. Med J Islam Repub Iran 2015; 29:187.
17. Pourbabaki R, Khadem M, Samiei S, Hasanpour H, Shahtaheri SJ. The protective effect of rosemary in mitigating oxidative stress induced by Chlorpyrifos in rat kidney. J Health Saf Work 2020; 10:24-29.
18. Farsani M, Dakhili M, Ababzadeh S, Yeganehparast M, Heidari F. Histomorphological and histochemical effects of diet with Qom zeolite on the tissue structure of the small intestine of broiler chickens compared with commercial zeolite. J Vet Res 2019; 74.
19. Hamidizad Z, Ababzadeh S, Heidari F, Haeri N-a-S, Eslami Farsani M, Sadegh M. Cobalamin modulate neurotoxic effects of trimethyltin chloride on hippocampus neural cells and cognitive function. Physiol Pharmacol 2019; 23:82-90.
20. Zhang X-Q, Wang X-Y, Dong B-C, Li M-X, Wang Y, Xiao T, et al. CXC chemokine receptor type 7 antibody enhances neural plasticity after ischemic stroke. Neural Regen Res 2023; 18:1976.
21. Ding L, Hao K, Sang L, Shen X, Zhang C, Fu D, et al. ATF2-driven osteogenic activity of enoxaparin sodium-loaded polymethylmethacrylate bone cement in femoral defect regeneration. J Orthop Surg Res 2023; 18:646.
22. Rubiolo JA, Mithieux G, Vega FV. Resveratrol protects primary rat hepatocytes against oxidative stress damage:: Activation of the Nrf2 transcription factor and augmented activities of anti-oxidant enzymes. Eur J Pharmacol 2008; 591:66-72.
23. Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Lower whole blood glutathione peroxidase (GPX) activity in depression, but not in myalgic encephalomyelitis/chronic fatigue syndrome: another pathway that may be associated with coronary artery disease and neuroprogression in depression. Neuro Endocrinol Lett 2010; 32:133-140.
24. Amirkhizi F, Siassi F, Djalali M, Foroushani AR. Assessment of anti-oxidant enzyme activities in erythrocytes of pre-hypertensive and hypertensive women. J Res Med Sci 2010; 15:270-278.
25. Marrocco I, Altieri F, Peluso I. Measurement and clinical significance of biomarkers of oxidative stress in humans. Oxid Med Cell Longev 2017; 2017.
26. Bilgin R, Kurt N, Gulesci N, Yucebilgic G. Age-related changes in anti-oxidant enzyme activities. Ann Clin Nutr 2020; 3:1016.
27. Al Sheyab FM, Abuharfeil N, Salloum L, Hani RB, Awad DS. The effect of Rosemary (Rosmarinus officinalis. L) plant extracts on the immune response and lipid profile in mice. J Biol Life Sci 2012; 3:37-58.
28. Loussouarn M, Krieger-Liszkay A, Svilar L, Bily A, Birtić S, Havaux M. Carnosic acid and carnosol, two major anti-oxidants of rosemary, act through different mechanisms. Plant Physiol 2017; 175:1381-1394.
29. Ramachandran C, Quirin K-W, Escalon E, Melnick SJ. Improved neuroprotective effects by combining Bacopa monnieri and Rosmarinus officinalis supercritical CO2 extracts. J Evid Based Complementary Altern Med 2014; 19:119-127.
30. Yashin A, Yashin Y, Xia X, Nemzer B. Anti-oxidant activity of spices and their impact on human health: A review. Anti-oxidants 2017; 6:70-87.
31. Posadas S, Caz V, Largo C, De la Gándara B, Matallanas B, Reglero G, et al. Protective effect of supercritical fluid rosemary extract, Rosmarinus officinalis, on anti-oxidants of major organs of aged rats. Exp Gerontol 2009; 44:383-389.
32. Waggas AM, Balawi AE. Neurophysiological study on possible protective effect of rosemary (Rosemarinus officinalis) Leaves Extract in male albino rats treated with acrylamide. Am-Eurasian J Sci Res 2008; 3:163-171.
33. Hussain S, Syeda A, Alshammari M, Alnasser S, Alenzi N, Alanazi S, et al. Cognition enhancing effect of rosemary (Rosmarinus officinalis L.) in lab animal studies: A systematic review and meta-analysis. Braz J Med Biol Res 2022; 55:e11593.
34. Maes M, Galecki P, Chang YS, Berk M. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro) degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35:676-692.
35. Suthammarak W, Somerlot BH, Opheim E, Sedensky M, Morgan PG. Novel interactions between mitochondrial superoxide dismutases and the electron transport chain. Aging Cell 2013; 12:1132-1140.
36. Kumar H, Lim H-W, More SV, Kim B-W, Koppula S, Kim IS, et al. The role of free radicals in the aging brain and Parkinson’s disease: convergence and parallelism. Int J Mol Sci 2012; 13:10478-10504.
37. Morterá P, Herculano-Houzel S. Age-related neuronal loss in the rat brain starts at the end of adolescence. Front Neuroanat 2012; 6:45.
38. Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clin Interv Aging 2018; 13:757.
39. Hantke N, Bott NT. Neuropsychology with older adults. Handbook Mental Health Aging 2020:257-275.
40. Shaw ME, Sachdev PS, Anstey KJ, Cherbuin N. Age-related cortical thinning in cognitively healthy individuals in their 60s: the PATH through life study. Neurobiol Aging 2016; 39:202-209.
41. Wisco JJ, Killiany RJ, Guttmann CR, Warfield SK, Moss MB, Rosene DL. An MRI study of age-related white and gray matter volume changes in the rhesus monkey. Neurobiol Aging 2008; 29:1563-1575.
42. Tian Q, Ferrucci L, Resnick SM, Simonsick EM, Shardell MD, Landman BA, et al. The effect of age and microstructural white matter integrity on lap time variation and fast-paced walking speed. Brain Imaging Behav 2016; 10:697-706.
43. Mohammadi H, Peng K, Kassab A, Nigam A, Bherer L, Lesage F, et al. Cortical thinning is associated with brain pulsatility in older adults: An MRI and NIRS study. Neurobiol Aging 2021; 106:103-118.
44. Harauz G, Ladizhansky V, Boggs JM. Structural polymorphism and multifunctionality of myelin basic protein. Biochemistry  2009; 48:8094-8104.
45. Harauz G, Boggs JM. Myelin management by the 18.5‐kDa and 21.5‐kDa classic myelin basic protein isoforms. J Neurochem 2013; 125:334-361.
46. Wake H, Lee PR, Fields RD. Control of local protein synthesis and initial events in myelination by action potentials. Science  2011; 333:1647-1651.