• KRITIKA KAUSHAL Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, India.
  • HARVINDER SINGH Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, India.
  • ANIL KANT Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, India.


Objective: Swertia chirata and Swertia cordata have been used in traditional and folk medicines to treat several mental disorders. However, the mechanistic and experimental justification to its traditional use is lacking. The present study was aimed to investigate the neuromodulatory potential of S. chirata and S. cordata during hypoxia-induced neuronal damage in Wistar rats and to determine the underlying mechanism.

Methods: Animals were divided into six groups (n=5). Hypoxia was inflicted by subjecting animals to the atmosphere having 10% O2 for 3 days. Animals were administered 100 mg/kg hydroalcoholic extract of S. chirata and S. cordata orally once daily for 7 days, after which motor coordination (Rotarod test) and memory functions (active avoidance test and passive avoidance test) were evaluated. Animals were sacrificed and biochemical investigations for oxidative stress and histopathology were performed.

Results: Subjecting animals to hypoxia resulted in marked memory dysfunction, and extract treatments improved memory functions in active avoidance and passive avoidance task. Hypoxiainduced the marked oxidative stress as indicated by the significantly elevated reactive oxygen species and lipid peroxidation and depleted catalase and glutathione levels in the hippocampus. S. chirata and S. cordata treatment alleviated oxidative stress in the hippocampus region of the brain. Brain histopathology confirmed that hypoxia resulted in significant neuronal damage and extract treatment efficiently rescued neurons from hypoxic damage. Overall, S. chirata extract treatment was observed to have better neuromodulatory effect than S. cordata during hypoxia.

Conclusion: Hypoxia induced memory dysfunction by inflicting neuronal damage and oxidative stress in the hippocampus region of the brain. The hydroalcoholic extract of S. chirata and S. cordata improved memory functions in hypoxic animals by alleviating hippocampal oxidative stress and by improving neuronal morphology and survival.

Keywords: Swertia chirata, Swertia cordata, Oxidative stress, Neurotoxicity, Hippocampus, Learning and memory.


1. Kossatz E, Silva-Peña D, Suárez J, de Fonseca FR, Maldonado R, Robledo P, et al. Octadecylpropyl sulfamide reduces neurodegeneration and restores the memory deficits induced by hypoxia-ischemia in mice. Front Pharmacol 2018;9:376.
2. Dong Y, Li Y, Feng D, Wang J, Wen H, Liu D, et al. Protective effect of HIF-1? against hippocampal apoptosis and cognitive dysfunction in an experimental rat model of subarachnoid hemorrhage. Brain Res 2013;1517:114-21.
3. Chhunchha B, Fatma N, Kubo E, Rai P, Singh SP, Singh DP, et al. Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells (HT22) by controlling prdx6 and NF-?B regulation. Am J Physiol Cell Physiol 2013; 304:C636 55.
4. Mehta V, Malairaman U. Flavonoids: Prospective strategy for the management of diabetes and its associated complications. In: Handbook of Research on Advancing Health Education through Technology. Hershey, PA: IGI Global; 2016. p. 286-328.
5. Mehta V, Parashar A, Udayabanu M. Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress. Physiol Behav 2017;171:69-78.
6. Huang WJ, Zhang X, Chen WW. Role of oxidative stress in alzheimer’s disease. Biomed Rep 2016;4:519-22.
7. Patel M. Targeting oxidative stress in central nervous system disorders. Trends Pharmacol Sci 2016;37:768-78.
8. Mehta V, Parashar A, Sharma A, Singh TR, Udayabanu M. Quercetin ameliorates chronic unpredicted stress-mediated memory dysfunction in male swiss albino mice by attenuating insulin resistance and elevating hippocampal GLUT4 levels independent of insulin receptor expression. Horm Behav 2017;89:13-22.
9. Bartsch T, Wulff P. The hippocampus in aging and disease: From plasticity to vulnerability. Neuroscience 2015;309:1-6.
10. Mehta V, Singh TR, Udayabanu M. Quercetin ameliorates chronic unpredicted stress-induced behavioral dysfunction in male swiss albino mice by modulating hippocampal insulin signaling pathway. Physiol Behav 2017;182:10-6.
11. Kumar V, Van Staden J. A review of Swertia chirayita (Gentianaceae) as a traditional medicinal plant. Front Pharmacol 2015;6:308.
12. Roy P, Abdulsalam FI, Pandey DK, Bhattacharjee A, Eruvaram NR, Malik T, et al. Evaluation of antioxidant, antibacterial, and antidiabetic potential of two traditional medicinal plants of India: Swertia cordata and Swertia chirayita. Pharm Res 2015;7:S57-62.
13. Khan AU, Rahim A, Iqbal Z, Gilani AH. Insights into mechanisms underlying the gut and airways modulatory effects of Swertia chirata. J Nat Med 2012;66:140-8.
14. Moscarello JM, LeDoux JE. Active avoidance learning requires prefrontal suppression of amygdala-mediated defensive reactions. J Neurosci 2013;33:3815-23.
15. Wasilewski M, Wojtczak L. Effects of N-acylethanolamines on the respiratory chain and production of reactive oxygen species in heart mitochondria. FEBS Lett 2005;579:4724-8.
16. Necheles TF, Maldonado N, Barquet-Chediak A, Allen DM. Homozygous erythrocyte glutathione-peroxidase deficiency: Clinical and biochemical studies. Blood 1969;33:164-9.
17. Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, et al. The role of oxidative stress and antioxidants in liver diseases. Int J Mol Sci 2015; 16:26087-124.
18. Anderson G, Maes M. Oxidative/nitrosative stress and immuno-inflammatory pathways in depression: Treatment implications. Curr Pharm Des 2014;20:3812-47.
19. Gan X, Wu L, Huang S, Zhong C, Shi H, Li G, et al. Oxidative stress-mediated activation of extracellular signal-regulated kinase contributes to mild cognitive impairment-related mitochondrial dysfunction. Free Radic Biol Med 2014;75:230-40.
20. Tramutola A, Lanzillotta C, Perluigi M, Butterfield DA. Oxidative stress, protein modification and alzheimer disease. Brain Res Bull 2017; 133:88-96.
21. Choi K, Kim J, Kim GW, Choi C. Oxidative stress-induced necrotic cell death via mitochondira-dependent burst of reactive oxygen species. Curr Neurovasc Res 2009;6:213-22.
22. Mukherjee D, Ghosh AK, Basu A, Datta S, Pattari SK, Bandyopadhyay A, et al. Beneficial role of melatonin in the complete recovery from isoproterenolinduced cardiac injury in rats. Int J Pharm Pharm Sci 2013; 5:561-9.
23. Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006;443:787-95.
24. Navarro A, Sánchez Del Pino MJ, Gómez C, Peralta JL, Boveris A. Behavioral dysfunction, brain oxidative stress, and impaired mitochondrial electron transfer in aging mice. Am J Physiol Regul Integr Comp Physiol 2002;282:R985-92.
25. Niizuma K, Endo H, Chan PH. Oxidative stress and mitochondrial dysfunction as determinants of ischemic neuronal death and survival. J Neurochem 2009;109 Suppl 1:133-8.
26. Farr SA, Poon HF, Dogrukol-Ak D, Drake J, Banks WA, Eyerman E, et al. The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J Neurochem 2003;84:1173-83.
27. Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ, et al. Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci 1999;19:8114-21.
28. Navarro A, Gomez C, López-Cepero JM, Boveris A. Beneficial effects of moderate exercise on mice aging: Survival, behavior, oxidative stress, and mitochondrial electron transfer. Am J Physiol Regul Integr Comp Physiol 2004;286:R505-11.
29. Kennedy DO, Wightman EL. Herbal extracts and phytochemicals: Plant secondary metabolites and the enhancement of human brain function. Adv Nutr 2011;2:32-50.
30. Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqvist-Tymchuk MR, Shukitt-Hale B, et al. Blueberry supplementation improves memory in older adults. J Agric Food Chem 2010;58:3996-4000.
31. Lee YK, Yuk DY, Lee JW, Lee SY, Ha TY, Oh KW, et al. (-)-epigallocatechin- 3-gallate prevents lipopolysaccharide-induced elevation of beta-amyloid generation and memory deficiency. Brain Res 2009;1250:164-74.
32. Babu SM, Swain S, Renuka K. Neuroprotective activity of fractional flower extracts of Mirabilis jalapa against aluminium hydrochloride induced neurotoxicity in male Wister rats. Int J Pharm Pharm Sci 2017; 9:216-21.
33. Kassab RB, Bauomy AA. The neuroprotective efficency of the aqueous extract of clove (Syzygium aromaticum) in aluniniuminduced neurotoxicity. Int J Pharm Pharm Sci 2014;6:503-8.
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How to Cite
KAUSHAL, K., H. SINGH, and A. KANT. “HYDROALCOHOLIC EXTRACT OF SWERTIA CHIRATA AND SWERTIA CORDATA ATTENUATES HYPOXIA-MEDIATED MEMORY DYSFUNCTION BY IMPROVING NEURONAL SURVIVAL IN WISTAR RATS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 2, Jan. 2019, pp. 356-62, doi:10.22159/ajpcr.2019.v12i2.29131.
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