The neuroprotective potential of ethanol:water (1:1) extract of rhizomes of Acorus calamus (AC–002) has been investigated in middle cerebral artery occlusion (MCAO)–induced ischaemia in rats. A significant behavioural impairment in Rota–Rod performance and grid walking was observed in rats, 72 hours after MCAO as compared to sham–operated animals. These rats also exhibited an increase in lipid peroxidation (cortex / 157%, corpus striatum – 58%) and a decrease in glutathione levels (cortex – 59%, corpus striatum – 34%) and superoxide dismutase (SOD) activity (cortex – 64%, corpus striatum – 32%) as compared to sham–operated animals. Ischaemic rats treated with AC–002 (25 mg/kg, p.o.) exhibited a significant improvement in neurobehavioural performance viz. Rota–Rod performance and grid walking as compared to the MCAO group. Interestingly, treatment with AC–002 in MCAO rats significantly decreased malonaldialdehyde levels in cortex as compared to ischaemic rats. A significant increase in reduced glutathione levels and SOD activity was also observed both in cortex and corpus striatum in MCAO rats treated with AC–002 in comparison to MCAO rats. Treatment with AC–002 in MCAO rats also reduced the contralateral cortical infarct area (19%) as compared to MCAO rats (33%). Neurological function score was improved in the AC–002–treated rats as compared to the MCAO group. The results of the present study indicate the neuroprotective efficacy of A. calamus in the rat model of ischaemia.
1 Nishizawa Y . Glutamate release and neuronal damage in ischemia . Life Sci2001; 69: 369-381 .
2.
2 Rogers DC , Campbell CA , Stretton JL , Mackay KB . Correlation between motor impairment and infarct volume after permanent and transient middle artery occlusion in rat . Stroke1997; 28: 2060-2065 .
3.
3 Chan PH . Role of oxidants in ischemic brain damage . Stroke1996; 27: 1124-1129 .
4.
4 Chabrier P , Auguet M , Spinnewyn B , Auvin S , Cornet S , Demerle-Pallardy C , Guilmard-Favre C , Marin J , Pignol B , Gillard-Roubert V , Roussillot-Charnet C , Schulz J , Viossat I , Bigg D , Moncada S . BN 80933, a dual inhibitor of neuronal nitric oxide synthase and lipid peroxidation: a promising neuroprotective strategy . Proc Natl Acad Sci U S A1999; 96: 10824-10829 .
5.
5 Tortella FC , Britton P , Williams A , May C , Newman AH . Neuroprotection (focal ischemia) and neurotoxicity (electro-encephalographic) studies in rats with AHN649, a 3-amino analogue of dextromethorphan and low-affinity N-methyl-D-aspartate antagonist . J Pharmacol Exp Ther1999; 291: 399-408 .
6.
6 Castillo J , Rama R , Davalos A . Nitric oxide-related brain damage in ischemic stroke . Stroke2000; 31: 852-857 .
7.
7 Fisher M , Schaebitz W . An overview of stroke therapy. Past, present and future . Arch Intern Med2000; 160: 3196-3206 .
8.
8 Horn J , Limburg M . Calcium antagonists for ischemic stroke: a systematic review . Stroke2001; 32: 570-576 .
9.
9 Raghu V , Dempsey RJ , Bowen KK . Inhibition of inter-cellular adhesion molecule-1 protein expression by antisense oligonucleotides is neuroprotective after transient middle cerebral artery occlusion in rat . Stroke2004; 35: 179-184 .
10.
10 Kaste M . Thrombolysis in ischemic stroke: present and future. Role of combined therapy . Cerebrovasc Dis2001; 11: 55-59 .
11.
11 Martinez-Vila E , Sieira PI . Current status and perspectives of neuroprotection in ischemic stroke treatment . Cerebrovasc Dis2001; 11: 60-70 .
12.
12 Sinha K , Deogaonkar M , Jagannathan NR , Gupta YK . Effect of melatonin on ischemia reperfusion injury induced by middle cerebral artery occlusion in rat . Eur J Pharmacol2001; 428: 185-192 .
13.
13 Sinha K , Chaudhary G , Gupta YK . Protective effect of resveratrol against oxidative stress in middle cerebral artery model of stroke in rats . Life Sci2002; 28: 655–665 .
14.
14 Gupta YK , Chaudhary G , Sinha K . Enhanced protection by melatonin and meloxicam combination in middle cerebral artery occlusion model of acute ischemic stroke in rat . Can J Physiol Pharmacol2002; 80: 210-217 .
15.
15 Gupta YK , Sinha K , Chaudhary G , Jagannathan NR . Protective effect of adenosine against neuronal injury induced by middle cerebral artery occlusion in rats as evidenced by diffusion weighted imaging . Pharmacol Biochem Behav2002; 72: 569-574 .
16.
16 Gong X , Sucher NJ . Stroke therapy in traditional Chinese medicine (TCM): prospects for drug discovery and development . Trends Pharmacol Sci1999; 20: 191-198 .
17.
17 Chaudhary G , Sharma U , Jagannathan NR , Gupta YK . Evaluation of Withania somnifera in a middle cerebral artery occlusion model of stroke in rats . Clin Exp Pharmacol Physiol2003; 30: 399-404 .
18.
18 Vohora SB , Shah SA , Dandiya PC . Central nervous system studies on an ethanol extract of Acorus calamus rhizomes . J Ethnopharmacol1990; 28: 53-62 .
19.
19 Martis G , Rao A , Karanth KS . Neuropharmacological activity of Acorus calamus . Fitoterapia1991; 4: 331–337 .
20.
20 Shukla PK , Khanna VK , Ali MM , Maurya R , Handa SS , Srimal RC . Protective effect of Acorus calamus against acrylamide induced neurotoxicity . Phytother Res2002; 16: 256-260 .
21.
21 Hazra R , Guha D . Acorus calamus: a traditional Indian herb and its role on ferric chloride induced experimental epileptic rat model . Ann Neurosci2005; 13: 21-21 (Abstract O7).
22.
22 Longa EZ , Weinstein PR , Carlson S , Cummins R . Reversible middle cerebral artery occlusion without craniotomy in rats . Stroke1989; 20: 84-91 .
23.
23 Glowinski J , Iverson LL . Regional studies of catecholamines in the rat brain. The deposition of 3H-norepinephrine, 3H-dopamine, and 3H-dopa in various regions of the brain . J Neurochem1966; 13: 655-659 .
24.
24 Bohme DH , Kosechzi R , Carsen S , Stern F , Marks N . Lipid peroxidation in human and rat brain tissue: developmental and regional studies . Brain Res1977; 136: 11-21 .
25.
25 Hasan M , Haider SS . Acetyl-homocysteine thiolactone protects against some neurotoxic effects of thallium . Neurotoxicology1989; 10: 257-262 .
26.
26 Kakkar P , Das B , Viswanathan PN . A modified spectrophotometric assay of superoxide dismutase . Ind J Biochem Biophys1984; 21: 130-132 .
27.
27 Lowry OH , Rosebrough NJ , Forr AL , Randall R . Protein measurement with the folin phenol reagent . J Biol Chem1951; 193: 265-275 .
28.
28 Liu TH , Kato H , Araki T , Itoyama Y , Kato K , Kogure K . An immunohistochemical study of copper/zinc superoxide dismutase and manganese superoxide dismutase following focal cerebral ischemia in the rat . Brain Res1994; 644: 257-266 .
29.
29 Traystman RJ , Kirsch JR , Koehler RC . Oxygen radical mechanisms of brain injury following ischemia and reperfusion . J Appl Physiol1991; 71: 1185-1195 .
30.
30 Hall ED . Antioxidant pharmacotherapy. In Ginsberg MD , Bogousslavsky J eds. Cerebrovascular disease: pathophysiology diagnosis and management. Blackwell, 1998: 710–720.
31.
31 Pierre S , Jamme I , Droy-Lefaix M-T , Nauvelot A , Maixent JM . Ginko biloba (EGb 761) protects Na, K ATPase activity during cerebral ischemia in mice . Neuroreport1999; 10: 47-51 .
32.
32 Curtis-Prior P , Vere D , Fray P . Therapeutic value of Ginko biloba in reducing symptoms of decline in mental function . J Pharm Pharmacol1999; 51: 535–541 .
33.
33 Wang Y , Chang CF , Chen HL , Deng X , Harvey BK , Cadet JL , Bickford PC . Dietary supplementation with blueberries, spinach or spirulina reduces ischemic brain damage . Exp Neurol2005; 193: 75-84 .
34.
34 Hara H , Kato H , Kogure K . a-Tocopherol on ischemic neuronal damage in the gerbil hippocampus . Brain Res1990; 510: 335-338 .
35.
35 Huh PW , Belayev L , Zhao W , Clemens JA , Panetta JA , Busto R , Ginsberg MD . Neuroprotection by LY341122, a novel inhibitor of lipid peroxidation, against focal ischemia brain damage in rat brain . Eur J Pharmacol2000; 389: 79-88 .
36.
36 Callaway JK , Knight MJ , Watkins DJ , Beart PM , Jarrott BJ . Delayed treatment with AM-36, a novel neuroprotective agent, reduces neuronal damage after endothelin-1-induced middle cerebral artery occlusion in conscious rats . Stroke1999; 30: 2704-2712 .
37.
37 Bederson JB , Pitts LH , Tsuji M , Nishimura MC , Davis RL , Bartkowski H . Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination . Stroke1986; 17: 472-476 .
38.
38 De Ryck M , Van Reempts J , Borgers M , Wauquier A , Janssen PJ . Photochemical stroke model: flunarizine prevents sensorimotor deficits after neocortical infarcts in rat . Stroke1989; 20: 1383-1390 .
39.
39 Markgraf CG , Green EJ , Watson B , McCabe PM , Schneiderman N , Dietrich WD , Ginsberg MD . Recovery of sensorimotor function after distal middle cerebral artery photothrombotic occlusion in rat . Stroke1994; 25: 153-159 .
40.
40 Belayev L , Alonso OF , Busto R , Zhao W , Ginsberg MD . Middle cerebral artery occlusion model in rat by intraluminal suture Neurological and pathological evaluation of an improved model . Stroke1996; 27: 1616-1622 .
41.
41 Zhao W , Belayev L , Ginsberg MD . Transient middle cerebral artery occlusion by intraluminal suture: II. Neurological deficits and pixel-based correlation of histopathology with local blood flow and glucose utilization . J Cereb Blood Flow Metab1997; 17: 1281-1290 .
