Effect of Cyperus rotundus on ischemia-induced brain damage and memory dysfunction in rats


1 Research Institute for Islamic and Complementary Medicine, Iran University of Medical Science, Tehran, Iran

2 Genetic Department, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran

3 Biology Department, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran

4 Anatomy Department, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran

5 School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Objective(s):Global cerebral ischemia-reperfusion injury causes loss of pyramidal cells in CA1 region of hippocampus. In this study, we investigated the possible neuroprotective effects of the ethanol extract of Cyperus rotundus (EECR) on a model of global transient ischemia in rat, by evaluating the pathophysiology of the hippocampal tissue and spatial memory.
Materials and Methods: Treatment group (EECR, 100 mg/kg/day) was gavaged from 4 days before, to 3 days after ischemia. Morris water maze test was performed 1 week after ischemia for 4 days. Brain tissue was prepared for Nissl staining.
Results: Our data showed no statistical difference between the treatment and ischemia groups in water maze task. So, treatment of ischemia with EECR cannot improve spatial learning and memory. On the contrary EECR ameliorated the CA1 pyramidal cell loss due to transient global ischemia/ reperfusion injury.
Conclusion: These results suggest that EECR cannot reduce the ischemia-induced, cognitive impairments seen after transient, global cerebral ischemia but can prevent pyramidal cell loss in CA1 region of hippocampus.


1. Di Carlo A. Human and economic burden of stroke. Age Ageing 2009; 38:4-5.
2. Sturm JW, Donnan GA, Dewey HM, Macdonell RA, Gilligan AK, Srikanth Vet al. Quality of life after stroke: the North East Melbourne Stroke Incidence Study (NEMESIS). Stroke 2004; 35:2340-2345. 
3. Collino M, Patel NS, Thiemermann C. PPARs as new therapeutic targets for the treatment of cerebral ischemia/reperfusion injury. Ther Adv Cardiovasc Dis 2008; 2:179-197. 
4. LongstrethJr WT, Dikmen SS. Outcomes after cardiac arrest. Ann Emerg Med1993; 22:64-69.
5. Lagali PS, Corcoran CP, Picketts DJ. Hippocampus development and function: role of epigenetic factors and implications for cognitive disease. Clin Gene 2010; 78:321-333.
6. Pulsinelli WA, Brierley JB, Plum F. Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neuro 1982; 11:491-498.
7. Chen J, Nagayama T, Jin K, Stetler RA, Zhu RL, Graham SH, et al. Induction of caspase-3-like protease may mediate delayed neuronal death in the hippocampus after transient cerebral ischemia. J Neurosci 1998; 18:4914-4928.
8. del Zoppo G, Ginis I, Hallenbeck JM, Iadecola C, Wang X, Feuerstein GZ. Inflammation and stroke: putative role for cytokines, adhesion molecules and iNOS in brain response to ischemia. Brain Pathol 2000; 10:95-112.
9. Allan SM, Rothwell NJ. Cytokines and acute neurodegeneration. Nat Rev Neurosci 2001; 2:734-744.
10. Iadecola C, Alexander M. Cerebral ischemia and inflammation. Curr Opin Neurol 2001; 14:89-94.
11. Dirnagl U, Simon RP, Hallenbeck JM. Ischemic tolerance and endogenous neuroprotection. Trends Neurosci 2003; 26:248-254.
12. Zheng Z, Yenari MA. Post-ischemic inflammation: molecular mechanisms and therapeutic implications. Neurol Res 2004; 26:884-892.
13. Zhu Y, Saito K, Murakami Y, Asano M, Iwakura Y, Seishima M. Early increase in mRNA levels of pro-inflammatory cytokines and their interactions in the mouse hippocampus after transient global ischemia. Neurosci Lett 2006; 393:122-126.
14. Kuang G, He Q, Zhang Y, Zhuang R, Xiang A, Jiang Q, et al. Modulation of Preactivation of PPAR-β on Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion. PPAR Res 2012; 2012:209794.
15. Lipton P. Ischemic cell death in brain neurons. Physiol Rev 1999; 79:1431-1568.
16. Sunil AG, Kesavanarayanan KS, Kalaivani P, Sathiya S, Ranju V, Priya RJ, et al. Total oligomeric flavonoids of Cyperusrotundus ameliorates neurological deficits, excitotoxicity and behavioral alterations induced by cerebral ischemic-reperfusion injury in rats. Brain Res Bull 2011; 84:394-405.
17. Pal D, Dutta S, Sarkar A. Evaluation of CNS activities of ethanol extract of roots and rhizomes of Cyperus rotundus in mice. Acta Pol Pharm 2009; 66:535-541.
18. Tona L, Kambu K, Ngimbi N, Cimanga K, Vlietinck AJ. Antiamoebic and phytochemical screening of some Congolese medicinal plants. J Ethnopharmacol 1998; 61:57-65.
20. Movassaghi S, Sharifi ZN, Soleimani M, Joghataei MT, Hashemi M, Shafaroodi H, et al. Effect of pentoxifylline on ischemia- induced brain damage and spatial memory impairment in rat. Iran J Basic Med Sci 2012; 15:1083-1090.
21. Tanabe M, Watanabe T, Ishibashi M, Hirano N, Tabuchi S, Takigawa H. Hippocampal ischemia in a patient who experienced transient global amnesia after undergoing cerebral angiography. Case illustration. J Neurosurg 1999; 91:347.
22. Colbourne F, Li H, Buchan AM, Clemens JA. Continuing postischemic neuronal death in CA1: influence of ischemia duration and cytoprotective doses of NBQX and SNX-111 in rats. Stroke 1999; 30:662-668.
23. Bendel O, Bueters T, von Euler M, Ögren SO, Sandin J, von Euler G. Reappearance of hippocampal CA1 neurons after ischemia is associated with recovery of learning and memory. J Cereb Blood Flow Metab 2005; 25:1586-1595.
24. Von Euler M, Bendel O, Bueters T, Sandin J, Von Euler G. Profound but transient deficits in learning and memory after global ischemia using novel water maze test. Behav Brain Res 2006; 166:204-210.
25. Mergenthaler P, Dirnagl U, Meisel A. Pathophysiology of stroke: lessons from animal models. Metab Brain Dis 2004; 19:151-167.
26. Sugawara T, Chan PH. Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia. Antioxid Redox Signal 2003; 5:597-607.
27. Seo WG, Pae HO, Oh GS, Chai KY, Kwon TO, Yun YG,  et al. Inhibitory effects of methanol extract of Cyperus rotundus rhizomes on nitric oxide and superoxide productions by murine macrophage cell line, RAW 264.7 cells. J Ethnopharmacol 2001; 76:59-64.
28. Koh PO. Melatonin regulates nitric oxide synthase expression in ischemic brain injury. J Vet Med Sci 2008; 70:747-750.
29. Zhang YB, Kan MY, Yang ZH, Ding WL, Yi J, Chen HZ, et al. Neuroprotective effects of N-stearoyltyrosine on transient global cerebral ischemia in gerbils. Brain Res 2009; 1287:146-156.
30. Kumar KH, Khanum F. Hydroalcoholic extract of Cyperus rotundus ameliorates H2O2-induced human neuronal cell damage via its anti-oxidative and anti-apoptotic machinery. Cell Mol Neurobiol 2013; 33:5-17.
31. Seo EJ, Lee DU, Kwak JH, Lee SM, Kim YS, Jung YS. Antiplatelet effects of Cyperusrotundus and its component (+)-nootkatone. J Ethnopharmacol 2011; 135:48-54.
32. Lee CH, Hwang DS, Kim HG, Oh H, Park H, Cho JH, et al. Protective effect of Cyperi rhizoma against 6-hydroxydopamine-induced neuronal damage. J Med
2010; 13:564-571. 
33. Singh N, Kulshrestha VK, Gupta MB, Bhargava KP. A pharmacological study of Cyperus rotundus. Indian J Med Res 1970; 58:103-109.
34. Singh N. Herbal medicine-science embraces tradition: a new insight into ancient Ayurveda. Saarbrücken: LAP Lambert Academic Publishing; 2010. P: 139-148.
35. Bachevalier J, Meunier M. Cerebral ischemia: are the memory deficits associated with hippocampal cell loss? Hippocampus 1999; 66:553-560.