EFFECT OF ORLISTAT ON LEARNING AND MEMORY IN NORMAL AND MEMORY DEFICIT ANIMALS
Keywords:
Nil, Orlistat, Phospholipase A2, Elevated Plus Maze, Rectangular Plus MazeAbstract
Objective: To investigate the possible effect of Orlistat on learning and memory in normal and memory deficit animals in two different age groups of mice.
Methods: The effect of Orlistat on learning and memory was evaluated using Elevated plus maze and Rectangular plus maze screening methods on young and adult mice.
Results: Three doses of Orlistat 5.4, 10.8 and 21.6 mg/kg, p. o were administered for 7 days and 15 days in experiments involving Elevated plus maze and Rectangular plus maze respectively in the separate group of animals. As a response to Elevated plus maze method adult and young mice showed the marked decrease in transfer latency (p<0.001) on 8th day when compared to negative control diazepam (1 mg/kg, i. p) indicating learning and retention of the learned task or memory in mice. Furthermore, in Rectangular plus maze the time taken by the mice to reach the reward chamber ‘B' from the entry chamber ‘A' in Orlistat treated animals was reduced. Orlistat 5.4 mg/kg did not show any significant impact on memory of young and old mice. Whereas Orlistat (10.8 and 21.6 mg/kg, p. o) dose proved to improve the memory in young as well as old mice.
Conclusion: This study shows that Orlistat possesses learning and memory improving activity by inhibiting phospholipase A2 in mice models.
Â
Downloads
References
Parle M, Dhingra D. Ascorbic Acid: a promising memory-enhancer in miceâ€. J Pharmacol Sci 2003;93(2):129-35.
Du J, Wang Z. Therapeutic potential of lipase inhibitor Orlistat in Alzheimer’s diseaseâ€. Med Hypotheses 2009;73(5):662-3.
Sanchez-Mejia RO, Mucke L. Phospholipase A2 and arachidonic acid in Alzheimer's diseaseâ€. Biochim Biophys Acta 2010;1801(8):784-90.
Kivipelto M, EL Helkala, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, et al. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based studyâ€. BMJ 2001;322(7300):1447.
Kivipelto M, Nagandu T, Fratiglioni L, Viitanen M, Kareholt I, Windlad B, EL Helkala, et al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer diseaseâ€. Arch Neurol 2005;62(10):1556–60.
Kivipelto M, Solomon A. Cholesterol as a risk factor for Alzheimer’s disease – epidemiological evidenceâ€. Acta Neurol Scand 2006;114(185):50–7.
Kwon CS, Sohn HY, Kim SH, Kim JH, Son JS, Lim JK, et al. Anti-obesity of Dioscoreo nopponica Makino with lipase-inhibitory activity in rodentsâ€. Biosci Biotechnol Biochem 2003;67(7):1451-6.
Yamamoto M, Shimura S, Itoh Y, Ohsaka T, Egawa M, Inoue S. Anti-Obesity effects of lipase inhibitor CT II, an extract from edible herbs, Nomane Herba, on rats fed a high-fat dietâ€. Int J Obesity 2000;24(6):758-64.
Carriere F, Renou C, Ransac S, Lopez V, Caro JD, Ferrato F, et al. Inhibition of gastrointestinal lipolysis by Orlistat during digestion of test meals in healthy volunteersâ€. Am J Physiol Gastrointest Liver Physiol 2001;281(1):G16-28.
Paget GE, Barnes JM. Evaluation of drug activities. In: Laurence DR, Bacharach AL. eds. Pharmacocosmeticsâ€. Academic press: New York and London; 1964. p. 1.
Isler D, Moeglen C, Gains N, Meier MK. Effect of the lipase inhibitor Olistat and of dietary lipid on the absorption of radiolabelled triolein, tri-gamma-linolenin and tripalmitin in miceâ€. Br J Nutr 1995;73(6):851-62.
Vasudevan M, Parle M. Pharmacological evidence for the potential of Daucus carota in the management of cognitive dysfunctionsâ€. Biol Pharm Bull 2006;29(6):1154-61.
Agarwal A, Malini S, Bairy KL, Rao MS. Effect of Tinospora cordifolia on learning and memory deficit ratsâ€. Indian J Pharmacol 2002;34:339-49.
Farooqui AA, Ong WY, Horrocks LA. Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disordersâ€. Pharmacol Rev 2006;58(3):591-20.
Nagy IZ. On the true role of oxygen free radicals in the living state, aging and degenerative disordersâ€. Ann NY Acad Sci 2001;928:187-99.
Lookene A, Skottova N, Olivecrona G. Interactions of lipoprotein lipase with the active-site inhibitor tetrahydrolipstatin (Orlistat)â€. Eur J Biochem 1994;222(2):395–03.
Bisogno T, Howell F, Williams G, Minassi A, Cascio MG, Ligresti A, et al. Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brainâ€. J Cell Biol 2003;163(3):463–8.
Bisogno T, Cascio MG, Saha B, Mahadeven A, Urbani P, Minassi A, et al. Development of the first potent and specific inhibitors of endocannabinoid biosynthesis. Biochim Biophys Acta 2006;1761(2):205–12.
Baum L, Chen L, Masliah E, Chan YS, Ng HK, Pang CP. Lipoprotein lipase mutations and Alzheimer’s diseaseâ€. Am J Med Genet 1999;88(2):136–9.
Farooqui AA, Liss L, Horrocks LA. Stimulation of lipolytic enzymes in Alzheimer’s diseaseâ€. Ann Neurol 1988;150:689-98.