ENTADA PHASEOLOIDES ATTENUATES SCOPOLAMINE INDUCED MEMORY IMPAIRMENT, NEURO-INFLAMMATION AND NEURO-DEGENERATION VIA BDNF/TRKB/NFΚB P65 PATHWAY IN RADIAL ARM MAZE

  • Chandana Choudhury Barua Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam 781022, India
  • Lipika Buragohain Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam 781022, India
  • Arundhati Purkayastha Department of Animal Biotechnology, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam 781022, India
  • Beenita Saikia Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam 781022, India
  • K Suresh Babu Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • G. Swarna Kumari Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India
  • Acheenta Gohain Barua Department of Veterinary Public Health, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam 781022, India

Abstract

Objective: The present study investigates the protective effects of crude extract from seeds of Entada phaseoloides and isolated compounds in enhancing cognition in Scopolamine induced learning and memory impairments in the radial arm maze model.

Methods: Two doses (100 and 200 mg/kg) of the crude methanolic extract of Entada phaseoloides (MEEP) were evaluated for amnesic activity by Radial Arm Maze memory model. Scopolamine (0.4 mg/kg i. p.), an amnestic drug was used for impairing memory. Tacrine (3 mg/kg, i. p.) was used as the standard drug. Animals were sacrificed to evaluate biochemical parameters viz. lipid peroxidase (LPO), nitrite oxide (NO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), cytokine levels by ELISA, Catecholamine levels by high performance liquid chromatography (HPLC), Caspase-3 activity by Fluorogenic assay, Gene (BDNF, TrkB, NF-κB p65, BAX) expression studies by Western Blotting and AChE, α7nAchR, Caspase-3, Nrf2 and HO-1 by Reverse Transcriptase Polymerase Chain Reaction.

Results: Treatment with MEEP significantly decreases escape latency and reference memory error (RME). MEEP treatment reversed the Scopolamine-induced hyperactivation of Acetylcholinesterase activity and overexpression of proteins NF-κB p65 BAX and also Caspase-3 activity in the hippocampus of rats. The level of BDNF, TrkB and α7nAchR were significantly up-regulated and AChE, Caspase-3, Nrf2, HO-1 were down-regulated in the MEEP treated rat. The extract increased the activity of SOD, GSH, Catalase, 5-HT, NE, Dopamine and decreased the levels of LPO and NO in rat hippocampus. Different active components of the seeds have been isolated.

Conclusion: These results indicated that seeds of Entada phaseoloides might become a promising therapeutic agent for the treatment of cognitive dysfunction in addition to its already established medicinal properties.

Keywords: Acetylcholinesterase, Catecholamine, Cholinergic, Entada phaseoloides, Scopolamine

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References

1. Patil M. Quantification of phytochemical constituents and in vitro antioxidant activity in the leaves of Citrus medica. Int J Curr Pharm Res 2017;9:119-23.
2. Maurya SK, Singh AK, Seth A. Potential medicinal plants for Lymphatic filariasis: a review. J Crit Rev 2015;5:1-6.
3. Kothari S, Singhal T. Docosahexaenoic acid administration ameliorates scopolamine-induced memory impairment in mice. Asian J Pharm Clin Res 2018;11:349-52.
4. Ikeda Y, Long DM. The molecular basis of brain injury and brain edema the role of oxygen radicals. Neurosurgery 1990;27:1-11.
5. El-Sherbiny DA, Khalifa AE, Attia AS, Eldenshary EEDS. Hypericum perforatum extract demonstrates antioxidant properties against elevated rat brain oxidative status induced by an amnestic dose of scopolamine. Pharmacol Biochem Behav 2003;76:525-33.
6. Mishima K, Tsukikawa H, Miura I, Inada K, Abe K, Matsumoto Y, et al. Ameliorative effect of NC-1900, a new AVP4-9 analog, through vasopressin V1A receptor on scopolamine-induced impairments of spatial memory in the eight-arm radial maze. Neuropharmacology 2003;44:541-52.
7. Kang SY, Lee KY, Park MJ, Kim YC, Markelonis GJ, Oh TH, et al. Decursin from Angelica gigas mitigates amnesia induced by scopolamine in mice. Neurobiol Learn Mem 2003;79:11-8.
8. Mohan VR, Janardhanan K. Chemical and nutritional evaluation of raw seeds of the tribal pulses Parkia roxburghii G. Don. and Entada phaseoloides (L.) Merr. Int J Food Sci Nutr 1993;44:47-53.
9. Kumar A. Entada phaseoloides (Linn.) Merr. syn. E. scandens: A glycoside of entagenic acid possesses anti-neoplastic activity. Science 2.0; 2009.
10. Ramakrishna D, Pavan KK, Mukkanti K, Abedulla KK. Antiulcer activity of the seeds of Entada phaseoloides. Pharmacologyonline 2008;3:93-9.
11. Ikram M, Babar ZM, Islam AMT, Chowdhury MAU, Uddin ME, Islam MR, et al. Antidiabetic and hypolipidemic effects of the different fractions of methanolic extracts of Entada phaseoloides (L.) Merr. In alloxan-induced diabetic mice. Int J Pharm Sci Res 2011;2:3160-5.
12. Liu WC, Kugelman M, Wilson RA, Roa KV. A crystalline saponin with antitumor activity from Entada phaseoloides, The John L. Smith Memorial Cancer Res 1972;11:171-3.
13. Li K, Xing S, Wang M, Peng Y, Dong Y, Li X. Anticomplement and antimicrobial activities of flavonoids from Entada phaseoloides. Nat Prod Commun 2012;7:867-71.
14. Dawane JS, Pandit V, Rajopadhye B, Karandikar M. The effect of two formulations of Entada phaseoloides seeds after topical application in ‘monoiodoacetate-induced osteoarthritis’ in rats. J Exp Integr Med 2013;3:37-41.
15. Esteban S, Garau C, Aparicio S, Moranta D, Barcelo P, Fiol MA. Chronic melatonin treatment and its precursor L-tryptophan improve the monoaminergic neurotransmission and related behaviour in the aged rat brain. J Pineal Res 2010a;48:170-7.
16. Esteban S, Garau C, Aparicio S, Moranta D, Barcelo P, Ramis M. Improving effects of long-term growth hormone treatment on monoaminergic neurotransmission and related behavioral tests in aged rats. Rejuvenation Res 2010b;13:707-16.
17. Bradford MM. A rapid and sensitive method for the quantisation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-54.
18. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxidation in animal tissues by the thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
19. Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide Biol Chem 2001;5:62-71.
20. Ellman GL. Tissue sulfhydryl groups. Agric Biochem Biophys 1959;82:70-7.
21. Marklund S, Marklund G. Involvement of the superoxide anion radical in the auto-oxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974;47:469-74.
22. Sinha AK. Colorimetric assay of catalase. Analytical Biochem 1972;47:389-94.
23. Sheikh MA, Noah MN, Tsuha K, Oomori T. Occurrence of tributyltin compounds and characteristics of heavy metals. Int J Environ Sci Tech 2007;4:49-59.
24. Yuqiong D, Haiming Shi, Haisha Y, Yunhua P, Mengyue W, Xiaobo L. Antioxidant phenolic compounds from the stems of Entada phaseoloides. Chem Biodivers 2012;9:68-79.
25. Scheff SW, Price DA, Schmitt FA, Mufson EJ. Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging 2006;27:1372-84.
26. Handral HK, Pandith A, Shruthi SD. A review on Murraya koenigii: Multipotential medicinal plant. Asian J Pharm Clin Res 2012;5:5-14.
27. Sutar RC, Kalaichelvan VK. Evaluation of antioxidant activity of leaf extracts of Holoptelea integrifolia (Roxb) planch. Int J Appl Pharma 2014;6:6-8.
28. Agrawal R, Tyagi E, Saxena G, Nath C. Cholinergic influence on memory stages: A study on scopolamine amnesic mice. Indian J Pharmacol 2009;41:192-6.
29. Giridharan VV, Thandavarayan RA, Sato S, Ko KM, Konishi T. Prevention of scopolamine-induced memory deficits by schisandrin B, an antioxidant lignan from Schisandra chinensis in mice. Free Radical Res 2011;45:950-8.
30. Harrison FE, Hosseini AH, Dawes SM, Weaver S, May JM. Ascorbic acid attenuates scopolamine-induced spatial learning deficits in the water maze. Behav Brain Res 2009;205:550-8.
31. Mattson MP, Pedersen WA, Duan W, Culmsee C, Camandola S. Cellular and molecular mechanisms underlying perturbed energy metabolism and neuronal degeneration in Alzheimer's and Parkinson's diseases. Ann N Y Acad Sci 1999;893:154-75.
32. Liu RH, Runyon RS, Wang YC, Oliver SG, Fan TP, Zhang WD. Deciphering ancient combinatorial formulas: the shexiang baoxin pill. Science 2015;347:540-2.
33. Rosales Corral S, Reiter RJ, Tan D, Ortiz GG, Lopez Armas G. Functional aspects of redox control during neuroinflammation. Antioxid Redox Signal 2010;13:193-247.
34. Muralidharan P, Balamurugan G, Venu B. Cerebroprotective effect of Glycyrrhiza glabra Linn. root extract on hypoxic rats. Bangladesh J Pharmacol 2009;4:60-4.
35. Hamazaki K, Hamazaki T, Inadera H. Fatty acid composition in the postmortem amygdala of patients with schizophrenia, bipolar disorder, and major depressive disorder. J Psychiatr Res 2012;46:1024-8.
36. Ochoa JJ, Pamplona R, Ramirez Tortosa MC, Granados Principal S, Perez Lopez P, Naudi A, et al. Age-related changes in brain mitochondrial DNA deletion and oxidative stress are differentially modulated by dietary fat type and coenzyme Q1. Free Radical Biol Med 2011;50:1053-64.
37. Haug A, Hostmark AT, Harstad OM. Bovine milk in human nutrition–a review. Lipids Health Disease 2007;6:25.
38. Suuronen T, Kolehmainen P, Salminen A. Protective effect of L-Deprenyl against apoptosis induced by okadaic acid in cultured neuronal cells. Biochem Pharmacol 2000;59:1589-95.
39. O'Bryant SE, Hobson V, Hall JR, Waring SC, Chan W, Massman P, et al. Brain­derived neurotrophic factor levels in Alzheimer's disease. J Alzheimers Dis 2009;17:337-41.
40. Garibotto V, Tettamanti M, Marcone A, Florea I, Panzacchi A, Moresco R, et al. Cholinergic activity correlates with reserve proxies in Alzheimer's disease. Neurobiol Aging 2013;34:2694.
41. Craig LA, Hong NS, McDonald RJ. Revisiting the cholinergic hypothesis in the development of Alzheimer's disease. Neurosci Biobehav Rev 2011;35:1397-409.
42. Cutuli D, Foti F, Mandolesi L, De Bartolo P, Gelfo F, Federico F, et al. Cognitive performances of cholinergically depleted rats following chronic donepezil administration. J Alzheimers Dis 2009;17:161-76.
43. Tota S, Hanif K, Kamat PK, Najmi AK, Nath C. Role of central angiotensin receptors in scopolamine-induced impairment in memory, cerebral blood flow, and cholinergic function. Psychopharmacol (Berl) 2012;222:185-202.
44. Doralp S, Leung LS. Cholinergic modulation of hippocampal CA1 basal-dendritic long-term potentiation. Neurobiol Learn Mem 2008;90:382-8.
45. Colovic MB, Krstic DZ, Lazarevic-Pasti TD, Bondzic AM, Vasic VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol 2013;11:315-35.
46. Brinton RD, Wang JM. Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer's disease: Allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res 2006;3:185-90.
47. Hagg T. From neurotransmitters to neurotrophic factors to neurogenesis. Neuroscientist 2009;15:20-7.
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Barua, C. C., L. Buragohain, A. Purkayastha, B. Saikia, K. S. Babu, G. S. Kumari, and A. G. Barua. “ENTADA PHASEOLOIDES ATTENUATES SCOPOLAMINE INDUCED MEMORY IMPAIRMENT, NEURO-INFLAMMATION AND NEURO-DEGENERATION VIA BDNF/TRKB/NFΚB P65 PATHWAY IN RADIAL ARM MAZE”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 10, no. 9, Sept. 2018, pp. 29-38, doi:10.22159/ijpps.2018v10i9.27487.
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