Pharmaspire


...

Pages: 20-27

Date of Publication: 30-Nov--0001

Orally administered chebulinic acid negated neurobehavioral deficits in intracerebroventricular streptozotocin and Amyloid-__ampersandsignbeta;-induced experimental model of dementia

Author: Rimpi Arora

Category: Pharmaceutics

[Download PDF]

Abstract:

Background: With the constant failure of the clinical trials and continuous exploration of a therapeutic target against Alzheimer’s disease (AD) is the utmost need. Chebulinic acid (ChA) has been reported to possess neuroprotective potential in various neurodegenerative models such as anxiety and depression. In the current study, the ChA was challenged on the progression of AD induced by intracerebroventricular (ICV)-streptozotocin (STZ)-and A__ampersandsignbeta; induced neurotoxicity to determine its therapeutic potential in experimental dementia. Material and Methods: STZ and A__ampersandsignbeta; were infused bilaterally (3 mg/kg/icv) on day 1st and 3rd after surgery. ChA (25, 50 and 100 mg/kg/p.o) was administered from 7th day onwards up to 21st day following 1st ICV-STZ and A__ampersandsignbeta; infusion. Cognitive impairment was evaluated by actophotometer, Morris water maze (MWM) and object recognition task (ORT) in rats whereas biochemical and neurochemical, using hipoocampal brain regions on day 22nd. Results: Ventricular administration of STZ and A__ampersandsignbeta; in rats found to significantly shorten the latency time on the MWM and ORT which was associated with significant alterations in hippocampal biochemistry, including elevation in oxidative stress and compromised antioxidant defense (reduced glutathione). Conclusion: ChA treatment significantly prevented the ICV-STZ and A__ampersandsignbeta; induced memory compromised antioxidant defense and cholinergic deficits in rats. These results clearly pointed to the pivotal role of ChA in ICV-STZ and A__ampersandsignbeta; induced neurotoxicity and its association may be a promising alternative to be investigated in the treatment of AD-like dementia.

Keywords: Alzheimer’s dementia, chebulinic acid, hippocampus, neuroprotection, streptozotocin

References:

1. Kalaria RN, Maestre GE, Arizaga R, Friedland RP, Galasko D, Hall K, et al. Alzheimer’s disease and vascular dementia in developing countries: Prevalence, management, and risk factors. Lancet Neurol 2008;7:812-26.

2. Lloyd-Jones DM, Leip EP, Larson MG, d’Agostino RB, Beiser A, Wilson PW, et al. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation 2006;113:791-8.

3. Picone P, Nuzzo D, Giacomazza D, Di Carlo M. β-amyloid peptide: The cell compartment multi-faceted interaction in Alzheimer’s disease. Neurotox Res 2020;37:250-63.

4. Du X, Wang X, Geng M. Alzheimer’s disease hypothesis and related therapies. Transl Neurodegener 2018;7:1-7.

5. Silvestrelli G, Lanari A, Parnetti L, Tomassoni D, Amenta F. Treatment of Alzheimer’s disease: From pharmacology to a better understanding of disease pathophysiology. Mech Ageing Dev 2006;127:148-57.

6. Vinters HV, Kleinschmidt-DeMasters BK, Love S, Louis DN, Ellison DW. General pathology of the central nervous system. In: Greenfield’s Neuropathology. United Kingdom: Taylor and Francis Group; 2008. p. 1-62.

7. Rahman SO, Panda BP, Parvez S, Kaundal M, Hussain S, Akhtar M, et al. Neuroprotective role of astaxanthin in hippocampal insulin resistance induced by Aβ peptides in animal model of Alzheimer’s disease. Biomed Pharmacother 2019;110:47-58.

8. Zhou S, Yu G, Chi L, Zhu J, Zhang W, Zhang Y, et al. Neuroprotective effects of edaravone on cognitive deficit, oxidative stress and tau hyperphosphorylation induced by intracerebroventricular streptozotocin in rats. Neurotoxicology 2013;38:136-45.

9. Sharma V, Bala A, Deshmukh R, Bedi KL, Sharma PL. Neuroprotective effect of RO-20-1724-a phosphodiesterase4 inhibitor against intracerebroventricular streptozotocin induced cognitive deficit and oxidative stress in rats. Pharmacol Biochem Behav 2012;101:239-45.

10. Gutierres JM, Carvalho FB, Schetinger MR, Marisco P, Agostinho P, Rodrigues M, et al. Anthocyanins restore behavioral and biochemical changes caused by streptozotocin-induced sporadic dementia of Alzheimer’s type. Life Sci 2014;96:7-17.

11. El Halawany AM, Sayed NS, Abdallah HM, El Dine RS. Protective effects of gingerol on streptozotocin-induced sporadic Alzheimer’s disease: Emphasis on inhibition of β-amyloid, COX-2, alpha-, beta-secretases and APH1a. Sci Rep 2017;7:1-1.

12. Verma N, Singh AP, Amresh G, Sahub PK, Singha A, Mishrab N. Review on wonderful and miraculous Triphala. J Pharm Res 2011;4:690-94.

13. Onasanwo S, Faborode SO, Agrawal M, Ijiwola OL, Jaiyesimi BO, NarenderT. Antidepressant and anxiolytic potentials of chebulinic acid in laboratory rodent. Ann Depress Anxiety 2014;1:1032.

14. Pfundstein B, El Desouky SK, Hull WE, Haubner R, Erben G, Owen RW. Polyphenolic compounds in the fruits of Egyptian medicinal plants (Terminalia bellerica, Terminalia chebula and Terminalia horrida): Characterization, quantitation and determination of antioxidant capacities. Phytochemistry 2010;71:1132-48.

15. Nampoothiri SV, Prathapan A, Cherian OL, Raghu KG, Venugopalan VV, Sundaresan A. In vitro antioxidant and inhibitory potential of Terminalia bellerica and Emblica officinalis fruits against LDL oxidation and key enzymes linked to Type 2 diabetes. Food Chem Toxicol 2011;49:125-31.

16. Yang MH, Vasquez Y, Ali Z, Khan IA, Khan SI. Constituents from Terminalia species increase PPARα and PPARγ levels and stimulate glucose uptake without enhancing adipocyte differentiation. J Ethnopharmacol 2013;149:490-8.

17. Sabu MC, Kuttan R. Anti-diabetic activity of medicinal plants and its relationship with their antioxidant property. J Ethnopharmacol 2002;81:155-60.

18. Lee HS, Jung SH, Yun BS, Lee KW. Isolation of chebulic acid from Terminalia chebula Retz. and its antioxidant effect in isolated rat hepatocytes. Arch Toxicol 2007;81:211-8.

19. Nair V, Singh S, Gupta YK. Anti?arthritic and disease modifying activity of Terminalia chebula Retz. in experimental models. J Pharm Pharmacol 2010;62:1801-6.

20. Nag G, De B. Acetylcholinesterase inhibitory activity of Terminalia chebula, Terminalia bellerica and Emblica officinalis and some phenolic compounds. Int J Pharm Pharm Sci 2011;3:121-4.

21. Chang CL, Lin CS. Phytochemical composition, antioxidant activity, and neuroprotective effect of Terminalia chebula Retzius extracts. Evid Based Complement Alternat Med 2012;2012:125247.

22. Chen Y, Tian Z, Liang Z, Sun S, Dai CL, Lee MH, et al. Brain gene expression of a sporadic (icv-STZ Mouse) and a familial mouse model (3xTg-AD mouse) of Alzheimer’s disease. PLoS One 2012;7:e51432.

23. Saleem A, Husheem M, Härkönen P, Pihlaja K. Inhibition of cancer cell growth by crude extract and the phenolics of Terminalia chebula retz. fruit. J Ethnopharmacol 2002;81:327-36.

24. Lee Y, Byun HS, Seok JH, Park KA, Won M, Seo W, et al. Terminalia chebula provides protection against dual modes of necroptotic and apoptotic cell death upon death receptor ligation. Sci Rep 2016;6:25094.

25. Silawat N, Gupta VB. Chebulic acid attenuates ischemia reperfusion induced biochemical alteration in diabetic rats. Pharm Biol 2013;51:23-9.

26. Hazra B, Sarkar R, Biswas S, Mandal N. Comparative study of the antioxidant and reactive oxygen species scavenging properties in the extracts of the fruits of Terminalia chebula, Terminalia belerica and Emblica officinalis. BMC Complement Altern Med 2010;10:20.

27. Arora R, Deshmukh R. Embelin attenuates intracerebroventricular streptozotocin-induced behavioral, biochemical, and neurochemical abnormalities in rats. Mol Neurobiol 2017;54:6670-80.

28. Frederickson CJ, Rampy BA, Reamy-Rampy S, Howell GA. Distribution of histochemically reactive zinc in the forebrain of the rat. J Chem Neuroanat 1992;5:521-30.

29. Deshmukh R, Sharma V, Mehan S, Sharma N, Bedi KL. Amelioration of intracerebroventricular streptozotocin induced cognitive dysfunction and oxidative stress by vinpocetine a PDE1 inhibitor. Eur J Pharmacol 2009;620:49-56.

30. Giorgetti M, Gibbons JA, Bernales S, Alfaro IE, La Rochelle CD, Cremers T, et al. Cognition-enhancing properties of Dimebon in a rat novel object recognition task are unlikely to be associated with acetylcholinesterase inhibition or N-methyl-D-aspartate receptor antagonism. J Pharmacol Exp Ther 2010;333:748-57.

31. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265-75.

32. Ellman GL, Courtney KD, Andres V Jr., Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7:88-95.

33. Wills ED. Mechanisms of lipid peroxide formation in animal tissues. Biochem J 1966;99:667-76.

34. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70-7.

35. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 1982;126:131-8.

36. Salkovic-Petrisic M, Osmanovic-Barilar J, Knezovic A, Hoyer S, Mosetter K, Reutter W. Long-term oral galactose treatment prevents cognitive deficits in male Wistar rats treated intracerebroventricularly with streptozotocin. Neuropharmacology 2014;77:68-80.

37. Mehla J, Pahuja M, Gupta YK. Streptozotocin-induced sporadic Alzheimer’s disease: selection of appropriate dose. J Alzheimers Dis 2013;33:17-21.

38. Rani V, Deshmukh R, Jaswal P, Kumar P, Bariwal J. Alzheimer’s disease: Is this a brain specific diabetic condition? Physiol Behav 2016;164:259-67.

39. Lu F, Li X, Li W, Wei K, Yao Y, Zhang Q, et al. Tetramethylpyrazine reverses intracerebroventricular streptozotocin-induced memory deficits by inhibiting GSK-3β. Acta Biochim Biophys Sin 2017;49:722-8.

40. Sun P, Ortega G, Tan Y, Hua Q, Riederer PF, Deckert J, et al. Streptozotocin impairs proliferation and differentiation of adult hippocampal neural stem cells in vitro-correlation with alterations in the expression of proteins associated with the insulin system. Front Aging Neurosci 2018;10:145.

41. Wang L, Wang J, Yang L, Zhou SM, Guan SY, Yang LK, et al. Effect of Praeruptorin C on 3-nitropropionic acid induced Huntington’s disease-like symptoms in mice. Biomed Pharmacother 2017;86:81-7.

42. Grieb P. Intracerebroventricular streptozotocin injections as a model of Alzheimer’s disease: In search of a relevant mechanism. Mol Neurobiol 2016;53:1741-52.

43. Federico A, Cardaioli E, Da Pozzo P, Formichi P, Gallus GN, Radi E. Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci 2012;322:254-62.