Salvia verticillata Improved Cognitive Deficits in a Chronic Cerebral Hypoperfusion Rat Model

Document Type : Research Article

Authors

• yalda Golriz ¹
• Amir Afkhami Goli ²
• Hamid Reza Sadeghnia ³
• Hossein Kazemi Mehrjerdi ⁴

¹ Graduated Student, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.

² Department of Basic Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.

³ Department of Basic Sciences, Mashhad University of Medical Sciences: Mashhad, Iran.

⁴ Department of Clinical Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.

10.22067/ijvst.2023.81804.1244

Abstract

CCH, resulting from multiple cerebrovascular diseases, has been considered the primary cause of cognitive impairment in recent years. In this process, oxidative stress plays a critical role and damages hippocampal neurons. Research has shown that Salvia verticillata has a significant antioxidant and free radical-scavenging activity due to its polyphenolic compounds. Therefore, the present study aimed to evaluate the effect of Salvia verticillata on a rat model of chronic cerebral hypoperfusion. A total of 24 rats were subjected to Salvia verticillata or vehicle orally from one week before 2VO surgery for 14 days. Cerebral hypoperfusion was induced by the bilateral occlusion of the common carotid arteries (2VO, n = 12 and sham, n = 12). The cognition of rats was evaluated 1 week after surgery in the MWM. In the MWM test, 2VO rats showed longer escape latency time and swimming distance and spent a shorter time in the target quadrant (p < 0.05). Moreover, we observed that Salvia verticillata treatment significantly reduced escape latency time, shortened the swimming distance, and increased target quadrant time (p > 0.05). Our results indicated that Salvia verticillata treatment significantly improved cognitive deficits in cerebral ischemic rats, probably by reducing oxidative stress damage.

Keywords

• Salvia verticillata
• rat
• hypoperfusion
• demancia

Main Subjects

• Pharmacology

---

References

1.    Duncombe J, Kitamura A, Hase Y, Ihara M, Kalaria RN, Horsburgh K. Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia. Clin Sci (Lond). 2017;131(19):2451-2468. doi: 10.1042/CS20160727.
2.    Fulop GA, Tarantini S, Yabluchanskiy A, Molnar A, Prodan CI, Kiss T, et al. Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular cognitive impairment. Am J Physiol Heart Circ Physiol. 2019;316(5):H1124-H40. doi: 10.1152/ajpheart.00776.2018.
3.    Zhou T, Lin L, Hao C, Liao W. Environmental enrichment rescues cognitive impairment with suppression of TLR4-p38MAPK signaling pathway in vascular dementia rats. Neurosci Lett. 2020;737:135318. doi: 10.1016/j.neulet.2020.135318.
4.    Farkas E, Luiten PG, Bari F. Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev. 2007;54(1):162-80. doi: 10.1016/j.brainresrev.2007.01.003. 
5.    Vicente É, Degerone D, Bohn L, Scornavaca F, Pimentel A, Leite MC, et al. Astroglial and cognitive effects of chronic cerebral hypoperfusion in the rat. Brain Res. 2009;1251:204-212.doi:  10.1016/j.brainres.2008.11.032. 
6.    Shibata M, Ohtani R, Ihara M, Tomimoto H. White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. Stroke. 2004;35(11):2598-2603. doi  10.1161/01.STR.0000143725.19053.60. 
7.    Yu W, Li Y, Hu J, Wu J, Huang Y. A study on the pathogenesis of vascular cognitive impairment and dementia: the chronic cerebral hypoperfusion hypothesis. J Clin Med. 2022;11(16):4742. doi: 10.3390/jcm11164742. 
8.  Rajeev V, Fann DY, Dinh QN, Kim HA, De Silva TM, Lai MK, et al. Pathophysiology of blood brain barrier dysfunction during chronic cerebral hypoperfusion in vascular cognitive impairment. Theranostics. 2022;12(4):1639-1658. doi 10.7150/thno.68304. 
9.    Fantini S, Sassaroli A, Tgavalekos KT, Kornbluth J. Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods. Neurophotonics. 2016;3(3):031411. doi:  10.1117/1.NPh.3.3.031411.
10.    Lana D, Ugolini F, Giovannini MG. An overview on the differential interplay among neurons–astrocytes–microglia in CA1 and CA3 hippocampus in hypoxia/ischemia. Front Cell Neurosci. 2020;14:585833. doi: 10.3389/fncel.2020.585833.
11.    Row BW, Liu R, Xu W, Kheirandish L, Gozal D. Intermittent hypoxia is associated with oxidative stress and spatial learning deficits in the rat. Am J Respir Crit Care Med. 2003;167(11):1548-1553. doi:  10.1164/rccm.200209-1050OC 
12.    Farkas E, Institóris Á, Domoki F, Mihály A, Luiten PG, Bari F. Diazoxide and dimethyl sulphoxide prevent cerebral hypoperfusion-related learning dysfunction and brain damage after carotid artery occlusion. Brain Res. 2004;1008(2):252-260. doi: 10.1016/j.brainres.2004.02.037.
13.    Jiwa NS, Garrard P, Hainsworth AH. Experimental models of vascular dementia and vascular cognitive impairment: a systematic review. J Neurochem. 2010;115(4):814-828. doi:  10.1111/j.1471-4159.2010.06958.x. 
14.    de la Torre JC, Aliev G. Inhibition of vascular nitric oxide after rat chronic brain hypoperfusion: spatial memory and immunocytochemical changes. J Cereb Blood Flow Metab. 2005;25(6):663-672. doi: 10.1038/sj.jcbfm.9600057.
15.    He X-L, Wang Y-H, Gao M, Li X-X, Zhang T-T, Du G-H. Baicalein protects rat brain mitochondria against chronic cerebral hypoperfusion-induced oxidative damage. Brain Res. 2009;1249:212-221. doi:10.1016/j.brainres.2008.10.005 
16.    Salzman R, Pacal L, Tomandl J, Kankova K, Tothova E, Gal B, et al. Elevated malondialdehyde correlates with the extent of primary tumor and predicts poor prognosis of oropharyngeal cancer. Anticancer Res. 2009;29(10):4227-31.
17.    Szczubial M KM, Albera E, Łopuszynski W, Dabrowski R. Oxidative/antioxidative status of blood plasma in bitches with mammary gland tumors. Bull Vet Inst Pulawy. 2008;52:255-9.
18. Faramarzi A, Seifi B, Sadeghipour HR, Shabanzadeh A, Ebrahimpoor M. Prooxidant-antioxidant balance and malondialdehyde over time in adult rats after tubal sterilization and vasectomy. Clin Exp Reprod Med. 2012;39(2):81-86. doi: 10.5653/cerm.2012.39.2.81. 
19.    Hajam YA, Rani R, Ganie SY, Sheikh TA, Javaid D, Qadri SS, et al. Oxidative stress in human pathology and aging: molecular mechanisms and perspectives. Cells. 2022;11(3):552. doi:  10.3390/cells11030552.
20.    Agarwal A, Gupta S, Sharma RK. Role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2005;3:28. doi:1186/1477-7827-3-28.
21.    Manikandan P, Al-Baradie R, Abdelhadi A, Al Othaim A, Vijayakumar R, Ibrahim R, et al. Neuroprotective effect of endophytic fungal antioxidant polyphenols on cerebral ischemic stroke-induced Albino rats; memory impairments, brain damage, and upregulation of metabolic proteins. J King Saud Univ Sci. 2023;35(1):102433. doi: 10.1016/j.jksus.2022.102433.
22.    Sunar S, Korkmaz M, SiĞmaz B, Ağar G. Determination of the genetic relationships among salvia species by RAPD and ISSR analyses. Turk J Pharm Sci. 2020;17(5):480-485. doi: 10.4274/tjps.galenos.2018.24572. 
23.    Capecka E, Mareczek A, Leja M. Antioxidant activity of fresh and dry herbs of some Lamiaceae species. Food Chem. 2005;93(2):223-6. doi:  10.1016/j.foodchem.2004.09.020.
24.    Šulniūtė V, Ragažinskienė O, Venskutonis PR. Comprehensive evaluation of antioxidant potential of 10 salvia species using high pressure methods for the isolation of lipophilic and hydrophilic plant fractions. Plant Foods for Hum Nutr. 2016;71(1):64-71. doi: 10.1007/s11130-015-0526-1.
25.    Orhan I, Kartal M, Naz Q, Ejaz A, Yilmaz G, Kan Y, et al. Antioxidant and anticholinesterase evaluation of selected Turkish Salvia species. Food Chem. 2007;103(4):1247-1254. doi: 10.1016/j.foodchem.2006.10.030.
26.    Tepe B. Antioxidant potentials and rosmarinic acid levels of the methanolic extracts of Salvia virgata (Jacq), Salvia staminea (Montbret & Aucher ex Bentham) and Salvia verbenaca (L.) from Turkey. Bioresour Technol. 2008;99(6):1584-1588. doi: 10.1016/j.biortech.2007.04.008.
27.    Mervić M, Bival Štefan M, Kindl M, Blažeković B, Marijan M, Vladimir-Knežević S. Comparative antioxidant, anti-acetylcholinesterase and anti-α-glucosidase activities of mediterranean salvia species. Plants. 2022;11(5):625. doi:  10.3390/plants11050625.
 28.    Tepe B. Antioxidant potentials and rosmarinic acid levels of the methanolic extracts of Salvia virgata (Jacq), Salvia staminea (Montbret & Aucher ex Bentham) and Salvia verbenaca (L.) from Turkey. Bioresour Technol. 2008;99(6):1584-1588. doi: 10.1016/j.biortech.2007.04.008.
29.    29. Grzegorczyk I, Matkowski A, Wysokińska H. Antioxidant activity of extracts from in vitro cultures of Salvia officinalis L. Food Chem. 2007;104(2):536-541.doi: 10.1016/j.foodchem.2006.12.003.
30. Matkowski A, Zielińska S, Oszmiański J, Lamer-Zarawska E. Antioxidant activity of extracts from leaves and roots of Salvia miltiorrhiza Bunge, S. przewalskii Maxim., and S. verticillata L. Bioresour Technol. 2008;99(16):7892-7896. doi:  10.1016/j.biortech.2008.02.013. 
31.    Mao M, Xu Y, Zhang XY, Yang L, An XB, Qu Y, et al. MicroRNA-195 prevents hippocampal microglial/macrophage polarization towards the M1 phenotype induced by chronic brain hypoperfusion through regulating CX3CL1/CX3CR1 signaling. J Neuroinflammation. 2020;17(1):1-20. doi: 10.1186/s12974-020-01919-w. 
32.    Wang DP, C SH, Wang D, Kang K, Wu YF, Su SH, et al. Neuroprotective effects of andrographolide on chronic cerebral hypoperfusion-induced hippocampal neuronal damage in rats possibly via PTEN/AKT signaling pathway. Acta Histochemica. 2020;122(3):151514. doi: 10.1016/j.acthis.2020.151514. 
33.    von Euler M, Bendel O, Bueters T, Sandin J, von Euler G. Profound but transient deficits in learning and memory after global ischemia using a novel water maze test. Behav Brain Res. 2006;166(2):204-210. doi: 10.1016/j.bbr.2005.07.016.
34.    Traystman RJ. Animal models of focal and global cerebral ischemia. ILAR journal. 2003;44(2):85-95. doi: 10.1093/ilar.44.2.85.
 35.    Sattayakhom A, Kalarat K, Rakmak T, Tapechum S, Monteil A, Punsawad C, et al. Effects of ceftriaxone on oxidative stress and inflammation in a rat model of chronic cerebral hypoperfusion. Behav Sci. 2022;12(8):287. doi:10.3390/bs12080287.
36. Shang Y-Z, Miao H, Cheng J-J, Qi J-M. Effects of amelioration of total flavonoids from stems and leaves of Scutellaria baicalensis Georgi on cognitive deficits, neuronal damage and free radicals disorder induced by cerebral ischemia in rats. Biol Pharm Bull. 2006;29(4):805-810. doi:10.1248/bpb.29.805.
 37.    Pappas B, De La Torre J, Davidson C, Keyes M, Fortin T. Chronic reduction of cerebral blood flow in the adult rat: late-emerging CA1 cell loss and memory dysfunction. Brain research. 1996;708(1-2):50-58. doi: 10.1016/0006-8993(95)01267-2.
38.    Hai J, Wan J-F, Lin Q, Wang F, Zhang L, Li H, et al. Cognitive dysfunction induced by chronic cerebral hypoperfusion in a rat model associated with arteriovenous malformations. Brain Res. 2009;1301:80-88. doi: 10.1016/j.brainres.2009.09.001.
39.    Ohta H, Nishikawa H, Kimura H, Anayama H, Miyamoto M. Chronic cerebral hypoperfusion by permanent internal carotid ligation produces learning impairment without brain damage in rats. Neuroscience. 1997;79(4):1039-1050. doi:10.1016/s0306-4522(97)00037-7.
40.Chao OY, Souza Silva M, Yang YM, Huston JP. The medial prefrontal cortex-hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties. Neurosci Biobehav Rev. 2020;113:373-407. doi:  10.1016/j.neubiorev.2020.04.007 
41.    Tosun M, Ercisli S, Sengul M, Ozer H, Polat T, Ozturk E. Antioxidant properties and total phenolic content of eight Salvia species from Turkey. Biol Res. 2009;42(2):175-81.42.
42.     Souri E FH, Ardestani S, Zolfagharifar M. Evaluation of antioxidant activity of methanolic extracts and some fractions of Salvia verticillata l. using three different methods. J Med Plants. 2007;6(21):20-25.