Praveen Kumar S E., K L Bairy, Veena Nayak, Mohandas Rao, Shiva Kumar Reddy, Abhijna Ballal, Aqsa Fathima
Praveen Kumar S E1., K L Bairy2, Veena Nayak1, Mohandas Rao3, Shiva Kumar Reddy4, Abhijna Ballal4, Aqsa Fathima1
1Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal. Karnataka, India 576104
2Associate Dean, and Chairperson, Pharmacology, RAK College of Medical Sciences, P.O. Box 11172,Ras Al Khaimah, UAE.
3Department of Anatomy, Melaka Manipal Medical College, Manipal.
4Centre for Molecular Neurosciences, Kasturba Medical College, Manipal. Manipal, Manipal Academy of Higher Education, Manipal. Karnataka, India 576104
Volume - 14,
Issue - 2,
Year - 2021
Background: Alzheimer’s disease (AD) is a geriatric neurodegenerative disorder, a common cause of dementia among older adults. Artemisinin and its derivatives (artesunate) have been proved to affect neuroinflammation at different concentrations. This study was aimed to investigate the effect of artesunate in aluminium chloride (AlCl3) induced AD. Objectives: To evaluate the effect of artesunate on learning and memory in experimentally induced AD in albino Wistar rats. Materials and Method: AD was induced in the rats by administration of 100 mg/kg bw. of aluminium chloride orally. Thirty albino Wistar rats were divided in to five groups (n=6), the groups I and II received distilled water (negative control) and AlCl3 (positive control) respectively for 60 days, groups III, IV and V were treated with AlCl3 for30 days followed by30 days of artesunate (28mg/kg bw), rivastigmine (1mg/kg bw), and memantine (20mg/kg bw) respectively along with AlCl3. Passive avoidance test (PAT) was used to test learning and memory on day 60 which was followed by histopathological examination of the hippocampus by Haematoxylin and Eosin staining (H and E). Results: The artesunate, rivastigmine, and memantine showed a protective effect in behavioural observations when compared to control and diseasegroups. These results were consistent with histopathological findings in the brain tissue. Conclusion: Artesunate has shown to have a promising effect in the aluminium chloride induced dementia model of AD comparable to the standard drugs.
Cite this article:
Praveen Kumar S E., K L Bairy, Veena Nayak, Mohandas Rao, Shiva Kumar Reddy, Abhijna Ballal, Aqsa Fathima. Effect of Artesunate in an animal model of Aluminium chloride induced Alzheimer’s Disease. Research J. Pharm. and Tech. 2021; 14(2):633-639. doi: 10.5958/0974-360X.2021.00113.X
1. Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet 2006; 368:387– 403.
2. Saba K, Rajnala N, Veeraiah P, Tiwari V, Rana RK, Lakhotia SC, Patel AB. Energetics of Excitatory and Inhibitory Neurotransmission in Aluminum Chloride Model of Alzheimer’s Disease: Reversal of Behavioral and Metabolic Deficits by Rasa Sindoor. Front. Mol. Neurosci. 2017; 10:323.
3. Senthil Venkatachalam, Ayush Jaiswal, Anindita De, Rohith Krishnan Vijayakumar. Repurposing Drugs for Management of Alzheimer Disease. Research J. Pharm. and Tech. 2019; 12(6):3078-3088
4. Lakshmi. K, Karishma. S K, N.S.S. Chandra Sekhar. G, Narendra Babu. A, Bhargav Kumar. N. Terminalia chebula Retz improve memory and learning in Alzheimer’s Model: (Experimental Study in Rat). Research J. Pharm. and Tech 2018; 11(11): 4888-4891.
5. VV Buchake, AP Muthal, RB Saudagar, RS Bachhav. A Neurodegenerative disorder-Alzheimer disease: A Treatise. Research J. Pharmacology and Pharmacodynamics. 2010; 2(4): 268-273
6. Kayalvili Sanmugam. Depression is a Risk Factor for Alzheimer Disease- Review. Research J. Pharm. and Tech. 8(8): August 2015; Page1056-1058.
7. Vasudev Pai, Chandrashekar K. S, C. S. Shreedhara, Aravinda Pai. In-Silico and In-Vitro correlation studies of natural β-secretase inhibitor: An approach towards Alzheimer’s Disease. Research J. Pharm. and Tech 2017; 10(10):3506-3510.
8. Singh NA, Bhardwaj V, Ravi C, Ramesh N, Mandal AKA, Khan ZA. EGCG Nanoparticles Attenuate Aluminium Chloride Induced Neurobehavioral Deficits, Beta-Amyloid and Tau Pathology in a Rat Model of Alzheimer’s Disease. Front. Aging Neurosci. 2018; 10:244
9. Singh, N. A., Mandal, A. K. A Khan, Z. A. Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG). Nutr. J. 2016; 15:60.
10. Saudagar RB, Buchake VV, Bachhav RS. Role of Retinoids in treatment of Alzheimer’s disease. Research J. Pharmacology and Pharmacodynamics. 2012; 4(3): 144-149.
11. Sobow T, Flirski M, Liberski PP. Amyloid-beta and tau proteins as biochemical markers of Alzheimer’s. Acta Neurobiologiae Experimentalis. 2004; 64:53-70.
12. Gandy S. The role of cerebral amyloid β accumulation in common forms of Alzheimer disease. J Clin Invest. 2005;115(5):1121-1129.
13. Okutake T, Kasuga K, Yajima R, Sekine Y, Tezuka T, Nishizawa M, Ikeuchi T. Hyperphosphorylation of Tau induced by naturally secreted amyloid-β at nanomolar concentrations is modulated by insulin-dependent Akt-GSK3β signalling pathway. J Biol Chem. 2012;287(42):35222-33.
14. M. Vijey Aanandhi, Yeshwanth Prasanna Kumar. B, Ranadheer Chowdary. P, Praveen. D. A Review on the Role of Presenilin in Alzheimer’s Disease. Research J. Pharm. and Tech 2018; 11(5):2149-2151.
15. Sree Lekshmi. R. S, P. Shanmugasundaram. Neuroprotective Properties of Statins. Research J. Pharm. and Tech 2018; 11(8): 3581-3584.
16. Malarkodi Velraj, N. Lavaniya. Alzheimer Disease and a Potential Role of Herbs-A Review. Research J. Pharm. and Tech 2018; 11(6): 2695-2700.
17. K. Periyanayagam, Gokila. S, K.G. Balasubramaniam, P.A.T. Jagatheeswary, J. Suriakumar, R. Parameshwari. Protective Effect of the Leaves of Solanumtorvumswartz on Drosophila melanogaster against β-Amyloid Induced Alzheimer Disease. Research J. Pharm. and Tech. 8(6): June 2015; Page 719-727.
18. M.O. Navamesa, L. Jiménezdíaz, J. Yajeya, J.D. Navarrolopez. GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimer’s disease. Front. Cell. Neurosci. 2014;8: 167.
19. S. Lista, S.E. O'Bryant, K. Blennow, B. Dubois, J. Hugon, H. Zetterberg, H. Hampel. Biomarkers in sporadic and familial Alzheimer’s disease. J. Alzheimer’s Dis. 2015;47: 291–317.
20. Ochmanski W, and Barabasz, W. Aluminium-occurrence and toxicity for organisms. Przeglad Lekarski. 2000;57(11), 665–668.
21. Yokel RA. The toxicology of aluminium in the brain: A review. Neurotoxicology. 2000; 21(5):813–828.
22. Kuroda Y, Kawahara M, Ichikawa M, Muramoto K, Kobayashi K, Mori H. Aluminium as a risk factor for Alzheimer’s disease – Aluminium causes accumulation of beta-amyloid protein and tau and loss of synapse in cortical neurons. J. Neurochem. 1993; 61:178.
23. Kandimalla R, Vallamkondu J, Corgiat EB, Gill KD. Understanding Aspects of Aluminium Exposure in Alzheimer's Disease Development. Brain Pathology. 2016; 26:139-54.
24. Bhattacharjee S, Zhao YH, Hill JM, Percy ME, Lukiw WJ. Aluminium and its potential contribution to Alzheimer's disease. Front Aging Neurosci. 2014; 6: 62.
25. Yunpeng Wei, Dan Liu, Yin Zheng, Honglian Li, Chaoshuang Hao, Wuqing Ouyang. Protective effects of kinetin against aluminium chloride and D-galactose induced cognitive impairment and oxidative damage in mouse. Brain Research Bulletin. 2017; 134:262-272
26. Pogue AI, Jones BM, Bhattacharjee S, Percy ME, Zhao YH, Lukiw WJ. Metal-Sulfate Induced Generation of ROS in Human Brain Cells: Detection Using an Isomeric Mixture of 5-and 6-Carboxy-2 ,7 -Dichlorofluorescein Diacetate (Carboxy-DCFDA) as a Cell Permeant Tracer. Int. J. Mol. Sci. 2012, 13, 9615-9626
27. Thenmozhi AJ, Dhivyabharathi M, Raja TRW, Manivasagam T, Essa MM. Tannoid principles of Emblica officinalis renovate cognitive deficits and attenuate amyloid pathologies against aluminium chloride induced rat model of Alzheimer's disease. Nutritional Neuroscience. 2016; 19:269-278.
28. Chiroma SM, Mohd Moklas MA, Mat Taib CN, Baharuldin MTH, Amon Z. D-Galactose and aluminium chloride induced rat model with cognitive impairments. Biomed and Pharmacother. 2018; 103:1602–1608.
29. Prema A, Justin Thenmozhi A, Manivasagam, T, Mohamed Essa M., Guillemin GJ. Fenugreek seed powder attenuated aluminium chloride induced tau pathology, oxidative stress, and inflammation in a rat model of Alzheimer’s disease. J. Alzheimers Dis. 2017; 60:209–220.
30. Shi JQ, Zhang CC, Sun XL, Cheng XX, Wang JB, Zhang YD, Xu J, Zou HQ. Antimalarial Drug Artemisinin Extenuates Amyloidogenesis and Neuroinflammation in APPswe/PS1dE9 Transgenic Mice via Inhibition of Nuclear Factor‐κB and NLRP3 Inflammasome Activation. CNS neuroscience and therapeutics. 2013;19(4):262-268.
31. Miranda AS, Brant F, Rocha NP, Cisalpino D, Rodrigues DH, Souza DG, Machado FS, Rachid MA, Teixeira Jr AL, Campos AC. Further evidence for an anti-inflammatory role of artesunate in experimental cerebral malaria. Malaria journal. 2013:2;12(1):388.
32. Ittarat W, Udomsangpetch R, Chotivanich KT, Looareesuwan S. The effects of quinine and artesunate treatment on plasma tumor necrosis factor levels in malaria-infected patients. Southeast Asian Journal of Tropical Medical Public Health. 1999; 30:7-10.
33. De Miranda AS, Lacerda-Queiroz N, De Carvalho VM, Rodrigues DH, Rachid MA, Quevedo J, Teixeira AL. Anxiety-like behavior and proinflammatory cytokine levels in the brain of C57BL/6 mice infected with Plasmodium berghei (strain ANKA). Neuroscilett. 2011;491(3):202-6.
34. Enciu AM, Popescu BO. Is there a causal link between inflammation and dementia? BioMed research international. 2013; 2013:316495.
35. Katafuchi T, Ifuku M, Mawatari S, Noda M, Miake K, Sugiyama M, Fujino T. Effects of plasmalogens on systemic lipopolysaccharide‐induced glial activation and β‐amyloid accumulation in adult mice. Ann N Y Acad Sci. 2012;1262(1):85-92
36. Hoozemans JJ, Rozemuller AJ, van Haastert ES, Eikelenboom P, van Gool WA. Neuroinflammation in Alzheimer's disease wanes with age. J neuroinflammation. 2011;8(1):171.
37. He P, Zhong Z, Lindholm K, Berning L, Lee W, Lemere C, Staufenbiel M, Li R, Shen Y. Deletion of tumor necrosis factor death receptor inhibits amyloid β generation and prevents learning and memory deficits in Alzheimer's mice. J Cell Biol. 2007;178(5):829-841.
38. Lim JE, Kou J, Song M, Pattanayak A, Jin J, Lalonde R, Fukuchi KI. MyD88 deficiency ameliorates β-amyloidosis in an animal model of Alzheimer's disease. Am J Pathol. 2011;179(3):1095-1103.
39. Krstic D, Madhusudan A, Doehner J, Vogel P, Notter T, Imhof C, Manalastas A, Hilfiker M, Pfister S, Schwerdel C, Riether C. Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice. J Neuroinflammation. 2012;9(1):151.
40. Sanjana K, Shyamjith M, Deepa B, Rao S, Pai P. Effect of artesunate on maximal electroshock and pentylenetetrazole-induced seizures in albino mice. Int. J. Green Pharm. 2012;6(1):63.
41. Kumar SP, Bairy KL, Nayak V, Reddy SK, Kiran A, Ballal A. Amelioration of Aluminium Chloride (AlCl3) Induced Neurotoxicity by Combination of Rivastigmine and Memantine with Artesunate in Albino Wistar Rats. Biomedical and Pharmacology Journal. 2019 Jun 25;12(2):703-11.
42. Pieta Dias C, Martins de Lima MN, Presti-Torres J, Dornelles A, Garcia VA, Siciliani Scalco F, Rewsaat Guimaraes M, Constantino L, Budni P, Dal-Pizzol F, Schroder N. Memantine reduces oxidative damage and enhances long-term recognition memory in aged rats. Neuroscience 2007; 146:1719-25.
43. Nampoothiri M, John J, Kumar N, Mudgal J, Nampurath GK, Chamallamudi MR. Modulatory role of simvastatin against aluminium chloride-induced behavioural and biochemical changes in rats. Behav. Neurol. 2015; 2015:210169.
44. Kumar P, Kumar A. Protective effect of rivastigmine against 3-nitropropionic acid-induced Huntington’s disease like symptoms: possible behavioural, biochemical and cellular alterations. Eur J of Pharmacol. 2009;615: 91–101.
45. Rai KS, Murthy KD, Karanth KS, Rao MS. Clitoriaternatea (Linn) root extract treatment during growth spurt period enhances learning and memory in rats. Indian J Physiolo Pharmacol. 2001;45(3):305-313.
46. Bharath G, Shalini Adiga, Shiva Kumar Reddy, Amruta Tripathy. Comparison of effects of carvedilol and propranolol on learning and memory in rats. International Journal of Advanced Research. 2015; 3 (10) :1164 – 1168.
47. Vijayalakshmi, Adiga S, Bhat P, Chaturvedi A, Bairy KL, Kamath S. Evaluation of the effect of Ferula asafoetida Linn. gum extract on learning and memory in Wistar rats. Indian J pharmacol. 2012 ;44(1):82-87.
48. Chetty S, Adiga S, Reddy S. Evaluation of the effect of costusigneus on learning and memory in normal and diabetic rats using passive avoidance task. International Journal of Pharmacy and Pharmaceutical Sciences. 2014 Jan 1; 6:835-838.
49. Maria Gladis Bupu Meze, Emy Koestanti Sabdoningrum, Sri Chusniati. Immune Response on the Spleen Histopathology of Mice (Mus musculus) Treated with (Brucellaabortus) Strain RB51 Vaccine and Infected with Brucellasuis. Research J. Pharm. and Tech. 2019; 12(11):5383-5388.
50. Wang Y, Huang Z, Wang L, Meng S, Fan Y, Chen T, Cao J, Jiang R, Wang C. The anti-malarial artemisinin inhibits pro-inflammatory cytokines via the NF-κB canonical signaling pathway in PMA-induced THP-1 monocytes. Int J Mol Med. 2011;27(2):233.
51. Xiong Z, Sun G, Zhu C, Cheng B, Zhang C, Ma Y, Dong Y. Artemisinin, an anti-malarial agent, inhibits rat cardiac hypertrophy via inhibition of NF-κB signaling. Eur J pharmacol. 2010;649(1):277-284.
52. Gugliandolo E, D’Amico R, Cordaro M, Fusco R, Siracusa R, Crupi R, Impellizzeri D, Cuzzocrea S and Di Paola R. Neuroprotective Effect of Artesunate in Experimental Model of Traumatic Brain Injury. Front. Neurol. 2018; 9:590.