Effect of Glabridin from Glycyrrhiza glabra on Learning and Memory in Mice

Abstract

Glabridin was isolated from the roots of Glycyrrhiza glabra and its effects on cognitive functions and cholinesterase activity were investigated in mice. Glabridin (1, 2 and 4 mg kg^-1, p. o.) and piracetam (400 mg kg^-1, i. p.), a clinically used nootropic agent, were administered daily for 3 successive days to different groups of mice. The higher doses (2 and 4 mg kg^-1, p. o.) of glabridin and piracetam significantly antagonized the amnesia induced by scopolamine (0.5 mg kg^-1, i. p.) in both the elevated plus maze test and passive avoidance test. Furthermore, glabridin (2 and 4 mg kg^-1, p. o.) and metrifonate (50 mg kg^-1, i. p.), used as a standard drug, both remarkably reduced the brain cholinesterase activity in mice compared to the control group. Therefore, glabridin appears to be a promising candidate for memory improvement and it will be worthwhile to explore the potential of glabridin in the management of Alzheimer patients.

Key words

Glabridin - Glycyrrhiza glabra - Leguminosae - cholinesterase - learning - memory

References

• 1 Haraguchi H, Yoshida N, Ishikawa H, Tamura Y, Mizutani K, Kinoshita T. Protection of mitochondrial functions against oxidative stresses by isoflavans from Glycyrrhiza glabra. .  J Pharm Pharmacol. 2000;  52 219-23
• 2 Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura T. Anti-Helicobacter pylori flavonoids from licorice extract.  Life Sci. 2002;  71 1449-63
• 3 Somjen D, Knoll E, Vaya J, Stern N, Tamir S. Estrogen-like activity of licorice root constituents: glabridin and glabrene, in vascular tissues in vitro and in vivo. .  J Steroid Biochem. 2004;  91 147-55
• 4 Yokota T, Nishio H, Kubota Y, Mizoguchi M. The inhibitory effect of glabridin from liquorice extracts on melanogenesis and inflammation.  Pigm Cell Res. 1998;  11 355-61
• 5 Dhingra D, Parle M, Kulkarni S K. Memory enhancing activity of Glycyrrhiza glabra in mice.  J Ethnopharmacol. 2004;  91 361-5
• 6 Parle M, Dhingra D, Kulkarni S K. Memory-strengthening activity of Glycyrrhiza glabra in exteroceptive and interoceptive behavioral models.  J Med Food. 2004;  7 462-6
• 7 Vaya J, Belinky P A, Aviram M. Antioxidant constituents from licorice roots: isolation, structure elucidation and antioxidative capacity toward LDL oxidation.  Free Radic Biol Med. 1997;  23 302-13
• 8 Parle M, Dhingra D. Ascorbic acid: a promising memory-enhancer in mice.  J Pharmacol Sci. 2003;  93 129-35
• 9 Dhingra D, Parle M, Kulkarni S K. Comparative brain cholinesterase inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic acid and metrifonate in mice.  J Med Food. 2006;  9 281-3
• 10 Itoh J, Nabeshima T, Kameyama T. Utility of an elevated plus maze for evaluation of nootripics, scopolamine and electroconvulsive shock.  Psychopharmacology. 1990;  101 27-33
• 11 Ghelardini C, Galeotti N, Barboloni A, Furukawa S. Memory facilitation and stimulation of endogenous nerve growth factor synthesis by the acetylcholine releaser PG-9.  J Pharmacol. 1998;  78 245-51
• 12 Bhattacharya S K, Upadhyay S N, Jaiswal A K. Effect of piracetam on electroshock induced amnesia and decrease in brain acetylcholine in rats.  Indian J Exp Biol. 1993;  31 822-4
• 13 Vasudevan M, Parle M. Pharmacological actions of Thespesia populnea relevant to Alzheimer's disease.  Phytomedicine. 2006;  13 677-87
• 14 Rao S K, Andrade C, Reddy K, Madappa K N, Thyagarajan S, Chandra S. Memory protective effect of indomethacin against electroconvulsive shockinduced retrograde amnesia in rats.  Biol Psychiatry. 2002;  51 770-3
• 15 Rogers E J, Milhalik S, Shea T B. Apple juice prevents oxidative stress and impaired cognitive performance caused by genetic and dietary deficiencies in mice.  J Nutr Health Aging. 2003;  7 1-6
• 16 Butterfield D A, Lauderback C M. Lipid peroxidation and protein oxidation in Alzheimer's disease: potential causes and consequences involving amyloid-beta peptideassociated free radical oxidative stress.  Free Radic Biol Med. 2002;  32 1050-60
• 17 Sayre L M, Zagorski M G, Surewicz W K, Krafft G A, Perry G. Mechanisms of neurotoxicity associated with amyloid beta deposition and the role of free radicals in the pathogenesis of Alzheimer's disease: a critical appraisal.  Chem Res Toxicol. 1997;  336 1216-22
• 18 Bickford P C, Gould T, Briederick L, Chadman K, Polloch A, Young D. et al . Antioxidants-rich diets improve cerebrellar physiology and motor learning in aged rats.  Brain Res. 2000;  886 211-7
• 19 Rosenblat M, Belinky P, Vaya J, Levy R, Hayek T, Coleman R. et al . Macrophage enrichment with the isoflavan glabridin inhibits NADPH oxidase-induced cell-mediated oxidation of low density lipoprotein.  J Biol Chem. 1999;  274 790-801