INTRODUCTION:

Alzheimer Disease is a chronic neurodegenerative disorder that is mainly generated by dementia syndrome, which affected mostly elderly people in middle age or above 60¹. During the early stages people lose memory and other symptoms like a way of behaving changes, forgot their routine works, difficulties in speaking and impaired communications². Alzheimer disease is an untreatable disorder and progressive course³. It is well developed by cognitive impairment, aggregates of amyloid beta (Aβ), synaptic failure and intraneuronal neurofibrillary tangles^4-6. In Alzheimer disease, plaques advanced within the hippocampus⁷, which makes easier to encrypt recollections and in different areas of the cerebral cortex it's miles applied to sell thinking skills and choice-making. The plaques are formed in spherical extracellular lesions which may have amyloid β-peptide fibrils through dystrophic axons, dendrites, activated microglia, and reactive astrocytes. Soluble amyloid βeta (Aβ) is normally generated by brain cells and it detached from the brain, in atypical conditions Aβ aggregates accommodate oligomers and amyloid fibrils.

It forms plaques, which bring reactive astrocytes and microglia^8-9. In the oxidative stress, the most common pathological features of Alzheimer Disease are oxidation of lipid, protein and nucleic acid in neurons. The neurons obtain masses of polyunsaturated fatty acids (PUFAs) particularly it is able to be correlated to reactive oxygen species (ROS) and results in a proliferation of lipid peroxidation and molecular destruction. Moreover, neurons incorporate low ranges of glutathione due to this low level of antioxidant (glutathione) the free radicals elimination is diminished¹⁰. An oxidative stress level is increased, it has been stated in the brains of non-demented aged and Alzheimer affected person. The observational method proposed that an antioxidant-rich diet will reduce the risk of Alzheimer Disease.

OXIDATIVE STRESS IS A FAMILIAR CHARACTERISTIC IN ALZHEIMER DISEASE:

Lipid Oxidation:

Phospholipid is rich in the brain. Phospholipids are made up of polyunsaturated fatty acid within the mind membrane and it carries a high proportion of PUFAs within the brain, mainly docosahexaenoic acid and arachidonic acid. The PUFAs contents in the brain slowly decrease and when a free radical production increases. Reduces in polyunsaturated fatty acid, predominantly in arachidonic acid and docosahexaenoic acid, it shows around lipid oxidation in Alzheimer disease^11-12.

Oxidation of polyunsaturated fatty acid produces aldehyde and it is one of the most prevailing in 4-hydroxynonenol. Brain membrane phospholipids are made up of polyunsaturated fatty acid, which is unusually exposed to free radical attack due to their double bond permit secure deletion of hydrogen ions. Increasing the level of 4-hydroxynonenol in autopsied specimen via multiple brain region and in the cerebral fluid is subjected to Alzheimer disease¹³. Glutathione transferases is a group of enzymes which may be inactive the toxic products of oxygen metabolism containing 4-hydroxyalkenals such as hydroxynonenal, are clearly reduced in multiple brain regions and in the CSF with Alzheimer Disease and it indicates a loss of defenses against HNE. Isoprostane manufacturing is the similarly improvement of lipid peroxidation. F2- isoprostane are prostaglandin that is composed by arachidonic acid via esterification. The oxidation of docosahexaenoic acid produced F4-neuroprostane. Increasing the levels of F2-IsoPs and F4-IsoPs is experimental within the cerebrospinal fluid (CSF), in Alzheimer disease^17-18.

Protein Oxidation:

Oxidation of protein plays an important role in Alzheimer disease. In Alzheimer disease brain there is an increased level of protein carbonyl, it denotes the oxidation damage to protein. Various studies indicate the protein carbonyl level is increased in multiple brain regions in theory with Alzheimer disease and in their NFTs. The tyrosine is answerable for many reactive oxygen and nitrogen species bring about the developed of three-nitrotyrosine and dityrosine. Mostly the 3-nitrotyrosine the rest attention in the CSF is negatively coordinate with the Mini-Mental State look at score¹⁹. Glutamine synthetase and creatine kinase is an enzyme which is particularly sensitive to oxidation and both the enzyme denotes that reduced in the brain of a subject with Alzheimer disease.

Nucleic Acid Oxidation:

DNA oxidation generates strand break, exchange of sister chromatids, cross-linking of DNA protein and improvement of base. Oxidation of DNA may lead to 8-OHdG development. The level of 8-OHdG in mitochondrial DNA isolated from the parietal cortex of patients with Alzheimer's disease is often three times improved compared to subjects with control. The DNA damage in a non-dividing mammalian cell and it plays the main role in aging-associated changes²⁰. RNA oxidation is also increased in the Alzheimer disease brain²¹. There is no other way to measure oxidation of DNA to determine breakage of the DNA strand. The level of DNA breakage in the brain cortex of AD patients is reported to be twice as high as in controls²².

This diagram conveys that the oxidative stress might be produce via mitochondrial dysfunction, inflammation, Aβ accumulation, Hyperphosphorylated tau, and metal malmetabolism in Alzheimer disease. The result of oxidative stress in the brain, such as 8-OHG, MDA and 4-HNE, could therefore be used for AD therapy. Finally, considering the oxidative stress plays a major role in Alzheimer Disease and antioxidants can be used for reduce the oxidative stress and improve treatment of Alzheimer disease.

ANTIOXIDANTS USED FOR ALZHEIMER’S DISEASE:

Antioxidant plays a vital role in treating Alzheimer disease. Antioxidant activity in lipoic acid, vitamin E, vitamin C and β-carotene has been identified as being used to break down intracellular and H₂O₂-cell-damaging compounds (i.e.) by-product of common functioning cells previously these radicals activate microglia or destroys cell around their actions as intracellular second messengers^23,24. However, an antioxidant also acts as a pro-oxidant beneath some illuminate position. Vitamin E is a pro-oxidant interest that was commonly defined in plasma lipoproteins at low concentrations of many oxidants.^26-28. Naturally, vitamin E blocks oxidation under strong oxidative conditions that trade to the attention of the vitamin as excessive variability of unfastened radicals²⁷. Copper and selenium as antioxidant properties of vitamin A and it may also become pro-oxidant between in vivo and in vitro. It is possible to examine the effect of prooxidant selenium in cultivated vascular cells. Nakamura et al., encouraged in the current study that vitamin C plays a critical role within the LDL oxidation pro-oxidant impact of vitamin E. Vitamin C is associated with ferrous iron and is a generally unfastened radical gadget. The food may comprises antioxidant is a better choice to intake of vitamin supplements. Therefore, pathogenesis studies are carried out and the mechanism of oxidative damage is essential in AD, the community survives among the many antioxidants and the correlation with each prooxidant and antioxidant factor. The situation is therefore focused specifically on the current progression of typically used antioxidant therapies for Alzheimer's disorder and guidelines for following potential antioxidant healing neurodegenerative disease techniques.

CHEMICAL STRUCTURE AND POTENTIAL FUNCTION OF THE ANTIOXIDANTS:

Vitamin E (α-tocopherol):

Vitamin E is a strong lipid-soluble chain-breaking antioxidant found in lipid membranes, circulating lipoproteins, and low-density lipoprotein (LDL) particles²⁹ and allows free-radical damage caused by toxic chain reactions in neuronal cells to be reduced and helps block dementia pathogenesis in mammalian cells.

Vitamin C:

Vitamin C as antioxidant property and it is highly water soluble. Vitamin C is an inhibitor of lipid peroxidation, which can be reacts as essential protection against free radicals in complete blood and plasma.

β- Carotene:

It is highly lipid soluble antioxidant. It is used to decreases the lipidperoxidation³⁰, which will improves the antioxidant level and quench singlet oxygen rapidly³¹. For example, lycopene is a beta carotene, which is used for an antioxidant and isolated from the tomato. It is liable for the red color in several consumed fruits and vegetables, it constitute more than 80% of total tomato carotenoids.

Caffeine:

Caffeine is an antioxidant it inhibit amyloidosis and production of Amyloid βeta. It decreases Aβ levels for early-onset Alzheimer's disease in the brain of transgenic mouse models.

Palmatine:

Palmatine is a well good antioxidant which shows the anti-Alzheimer Disease effects in both ChEs and Aβ pathways. It can inhibit ROS and RNS as well³².

Curcumin:

Curcumin is a bright yellow color produced by the rhizomatous herbaceous perennial plant (Curcuma longa) and it belongs to the ginger family, Zingiberaceae³³. Medicinal properties of turmeric are antioxidant, bioactive component, anti-inflammatory and anti-tumor³³. It is said that curcumin (1, 7-bis (4-hydroxy-3-methoxyphenyl)-1, 6-heptadiene-3, 5-dione) is diferuloylmethane. Curcumin shows anti-inflammatory activity which can be used to decrease the risk factor of Alzheimer Disease. It is organic active polyphenolic compound which is established in the rhizome of Curcuma longa (turmeric) and in others Curcuma spp. It is used as a medicinal property and health care for example, a curcumin research study helps the macrophages to eliminate the development of amyloid plaques in Alzheimer's disease³⁴. Curcumin has the potential to bind with Aβ and frustrate it’s self-build³⁵. Curcumin is founded as a promising drug in the treatment of Alzheimer Disease³⁷. Recently, Longvida, formulation of curcumin, might be evaluated in phase II Alzheimer’s clinical trial^38-42.

Resveratrol:

Resveratrol is a natural phenol and derived from a plant, number of foods including, blueberries, raspberries, red wine, dark chocolate and present in high amount in red grapes. Resveratrol is belonging to the family Vitaceae. It produces antioxidant activity at a high level. It shows in recent studies that resveratrol quickly passes into CNS after peripheral administration and can preserve neurons in the brain and spinal cord against ischemic injury^43-44. Resveratrol is closely linked to Alzheimer's disease in models and protects neuronal cells from amyloid β-peptide killing and stimulates amyloid β-peptide clearance from cultivated cells⁴⁵.

Ginkgo biloba L. (Ginkgoaceae):

Ginkgo biloba belongs to the family Ginkgoaceae. It contains neuroprotective activity and it is present in the perennial tree. Ginkgo biloba reduces free radical and increases memory power to the patient in Alzheimer disease (AD). It includes flavonoids that enhance memory power. Ginkgo biloba protects neurodegeneration and GABA inhibitory neurotransmission persuades by hippocampal corticosterone⁴⁷. Ginkgo biloba is consequently administered in the albino rat then it improves the memory power and learning skills⁴⁸.

Celastrus paniculatus:

Celastrus paniculatus is a plant belongs to the family Celastraceae, and it is commonly said to be a black-oil tree. Celastrus paniculatus as the antioxidant activity so it is protected neuronal cell damage against hydrogen peroxide toxicity and glutamine induced toxicity⁴⁹. And it also used to enhance the memory. Celastrus paniculatus increases cholinergic activities so it improves the memory power⁵⁰. Celastrus paniculatus extracts prevent neuronal cells from becoming toxic by antioxidant hydrogen peroxide and free radical scavenging.⁵¹.

Withania somnifera:

Withania somnifera, also known as Ashwagandha, Indian ginseng, gooseberry poison or winter cherry, can be found in the plant root. Withania somnifera belongs to the family Solanaceae. It is used to promote perception and memory power. Withania somnifera as antioxidant and anti-inflammatory activity. Ashwagandha increases dendrite and axon regeneration. A study of molecular modeling shows that withanamides A and C bind to Aβ and limit the synthesis of fibrils.

Convolvulus pluricaulis:

Convolvulus pluricaulis belongs to the family Convolvulaceae and it is commonly said to be Shahkpushpi. It is a reddish-yellow hairy herb that is approved for treating nervous disorders and as an anti-aging remedy by Ayurvedic practitioners. The entire extract of the plant comes from milk and cumin to treat fever, disability, loss of memory, syphilis and scrofula.

Centella asiatica:

Centella asiatica is a psychoactive medicinal plant that belongs to the family Apiaceae. The medicinal plant is used for a period of time in the ayurvedic system in the name of medhyarasayna and it reduces the oxidative stress in the brain. The plant triterpenoidsaponins is the most important bioactive compound and it is related to sapogenins. Centella asiatica is used to treat for the depression, rheumatism, mental weakness, abdominal pain, and epilepsy. And it is diuretic, anti-spasmodic, anti-convulsive, tonic, stimulant, antioxidant and spermatogenic. It reversed the Aβ pathology and minimized oxidative stress response. It is also used to promote learning and memory power.

THERAPEUTIC USES OF ANTIOXIDANT:

The hypothesis is most attractive because it is known that there are adequate free radical scavengers (e.g. vitamins E and C, Ginkgo biloba extract EGb 761, melatonin, flavonoids and carotenoids). Vitamin E (α-tocopherol), vitamin C, and β-carotene are exogenous chain-breaking antioxidants that can reduce free-radical-mediated damage in neuronal cells caused by toxic chain reactions and benefit from the frustration of dementia pathogenesis in mammalian cells. This assumption was confirmed by the use of a rational degree of success in both experimental and clinical conditions. Several experimental studies show that free radical-scavenging substances block β-amyloid's toxic effect on cell cultures and organotypic hippocampal culture. α-tocopherol is a most important lipid phase antioxidant. It is a powerful, lipid-soluble chain-breaking antioxidant known in lipid membranes, lipoproteins circulating and particles of low density lipoprotein (LDL). It shows vitamin E reduces the toxic effects of β-amyloid in experimental studies and improves cognitive performance in rodents. In 1997, Sano et al. designed that patients with Alzheimer's disease treated with α-tocopherol (2000 IU per day) which decreases neuronal damage and reduces the development of Alzheimer's disease and showed that the use of α-tocopherol in patients with Alzheimer's disease could detain clinically major functional decline. There is a synergistic interrelation between exposure to lipid peroxidation of vitamin C, vitamin E and carotenoids.

In addition, vitamin E, vitamin C and vitamin B12 could play a key role in Alzheimer's disease treatment. In many studies, the serum levels of vitamin B12 in patients with Alzheimer's disease remained particularly different from the control group, which can contribute in part to neuron degeneration. Numerous works showed that supplementation with vitamin B12 improved choline acetyltransferase activity in cholinergic neurons in cats and improved cognitive functions in patients with Alzheimer's disease.

CONCLUSION:

Oxidative damage to cellular molecules has been well found to play a major role in neurodegenerative disorder. Oxidative damage is not just a by-product or end product of the neuronal degenerative process, but initiates neurodegeneration. A recent research found that antioxidant is the most successive therapy in the Alzheimer disease. Till now, the antioxidant is the only one that shows the promising outcome of a moderately severe Alzheimer's disease trial of vitamin E therapy. Through the experimental studies are well-known that the antioxidant properties as the limited capacity to cross the blood-brain barrier. Therefore, the improvement of smaller antioxidant molecules which would allow more easily through the barrier and non-toxic or inert compounds which would take anti-oxidant drugs from the bloodstream into the brain is very promising. However, clinical trials for AD prevention and antioxidant treatment are still in their initial stages, the most common antioxidant drugs show common success in animal models. However, the approach of natural antioxidant is capable of targeting many dissimilar molecular events cooperation in the pathogenesis of Alzheimer disease treatment.

REFERENCES:

1. B. Klimova, K. Kuca, Alzheimer's disease: potential preventive, non-invasive, intervention strategies for lowering the risk of cognitive decline- a review study, J. Appl. Biomed. 13 (4) (2015) 257–261.

2. A. Alzheimer's, 2015- Alzheimer's disease facts and figures, Alzheimer's Dementia 11 (3) (2015) 332.

3. Dubois B, Feldman HH, Jacova C, et al., Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol. 2010; 9(11):1118–1127.

4. Md S, Bhattmisra SK, Zeeshan F, et al. Nano-carrier enabled drug delivery systems for a nose to brain targeting for the treatment of neurodegenerative disorders. J Drug Delivery Science Technol. 2018; 43:295–310.

5. Anand A, Patience AA, Sharma N, Khurana N. The present and future of pharmacotherapy of Alzheimer’s disease: A comprehensive review. Eur J Pharmacol. 2017; 815:364–375.

6. Sun D, Li N, Zhang W, et al. Design of PLGA-functionalized quercetin nanoparticles for potential use in Alzheimer’s disease. Colloids Surf B Biointerfaces. 2016; 148:116–129.

7. Fazil M, Md S, Haque S, et al. Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting. Eur J Pharm Sci. 2012; 47(1):6–15.

8. Petrella JR, Coleman RE, Doraiswamy PM. Neuroimaging and early diagnosis of Alzheimer disease: a look to the future. Radiology 2003; 226:315e36.

9. Alzheimer’s Association. 2013 Alzheimer’s disease facts and figures. Alzheimers Dement. 2013; 9(2):208–245.

10. Zhichun Chen, Chunjiu Zhong et al., Oxidative stress in Alzheimer's disease Neuroscience Bull April 1, 2014, 30(2): 271–281. Neuroscience Bull April 1, 2014, 30(2): 271 281.http://www. Neuroscience DOI: 10.1007/s12264-013-1423-y.

11. Skoumalova A, Hort J. Blood markers of oxidative stress in Alzheimer's disease. J Cell Mol Med 2012, 16: 2291–2300.

12. Soderberg M, Edlund C, Kristensson K, Dallner G. Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease. Lipids 1991, 26: 421–425.

13. Markesbery WR, Carney JM. Oxidative alteration in Alzheimer’s disease. Brain Pathol. 1999; 9: 133-139

14. Lovell MA, Ehmann WD, Butler SM, Markesbery WR. Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease. Neurology 1995, 45: 1594–1601.

15. Butterfield DA, Reed T, Perluigi M, De Marco C, Coccia R, Cini C, et al. Elevated protein-bound levels of the lipid peroxidation product, 4-hydroxy-2-nonenal, in brain from persons with mild cognitive impairment. Neurosci Lett 2006, 397: 170–173.

16. Keller JN, Schmitt FA, Scheff SW, Ding Q, Chen Q, Butterfield DA, et al. Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 2005, 64: 1152–1156.

17. Pratico D, Clark CM, Lee VM, Trojanowski JQ, Rokach J, FitzGerald GA. Increased 8, 12-iso-iPF2alpha-VI in Alzheimer's disease: correlation of a noninvasive index of lipid peroxidation with disease severity. Ann Neurol 2000, 48: 809–812.

18. Roberts LJ, 2nd, Montine TJ, Markesbery WR, Tapper AR, Hardy P, Chemtob S, et al. Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid. J Biol Chem 1998, 273: 13605–13612.

19. Roberts LJ, 2nd, Montine TJ, Markesbery WR, Tapper AR, Hardy P, Chemtob S, et al. Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid. J Biol Chem 1998, 273: 13605–13612.

20. Mecocci P, Mac Garvey U, Beal MF. Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease. Ann Neurol 1994, 36: 747–751.

21. Nunomura A, Perry G, Pappolla MA, Wade R, Hirai K, Chiba S, et al. RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer’s disease. J Neurosci 1999, 19: 1959 -1964.

22. Mullaart E, Boerrigter ME, Ravid R, Swaab DF, Vijg J. Increased levels of DNA breaks in cerebral cortex of Alzheimer's disease patients. Neurobiol Aging 1990, 11: 169–173.

23. H. B. Staehelin, “Micronutrients and Alzheimer’s disease,” Proceedings of the Nutrition Society, vol. 64, no. 4, pp. 565– 570, 2005.

24. M. Grundman, “Vitamin E and Alzheimer’s disease: the basis for additional clinical trials,” American Journal of Clinical Nutrition, vol. 71, pp. 630–636, 2000.

25. J. Neuzil, B. A. Darlow, T. E. Inder, K. B. Sluis, C. C. Winterbourn, and R. Stocker, “Oxidation of parenteral lipid emulsion by ambient and phototherapy lights: potential toxicity of routine parenteral feeding,” Journal of Pediatrics, vol. 126, no. 5, pp. 785–790, 1995.

26. R. Stocker, “Lipoprotein oxidation: mechanistic aspects, methodological approaches and clinical relevance,” Current Opinion in Lipidology, vol. 5. 422–433, 1994.

27. V. W. Bowry and R. Stocker, “Tocopherol- mediated peroxidation. The prooxidant effect of vitamin E on the radical initiated oxidation of human low-density lipoprotein,” Journal of the American Chemical Society, vol. 115, no. 14, pp. 6029–6044, 1993.

28. A. Kontush, B. Finckh, B. Karten, A. Kohlsch¨utter, and U. Beisiegel, “Antioxidant and prooxidant activity of α- tocopherol in human plasma and low density lipoprotein,” Journal of Lipid Research, vol. 37, no. 7, pp. 1436–1448, 1996.

29. C. J. Foy, A. P. Passmore, M. D. Vahidassr, I. S. Young, and J. T. Lawson, “Plasma chain-breaking antioxidants in Alzheimer’s disease, vascular dementia and Parkinson’s disease,” An International Journal of Medicine, vol. 92, no. 1, pp. 39–45, 1999.

30. J. E. Upritchard, C. R. W. C. Schuurman, A. Wiersma et al., “Spread supplemented with moderate doses of vitamin E and carotenoids reduces lipid peroxidation in healthy, nonsmoking adults,” American Journal of Clinical Nutrition, vol. 78, no. 5, pp. 985–992, 2003.

31. P. Di Mascio, M. E. Murphy, and H. Sies, “Antioxidant defense systems: the role of carotenoids, tocopherols, and thiols,” American Journal of Clinical Nutrition, vol. 53, no. 1, pp. 194S–200S, 1991.

32. H. A. Jung, B. S. Min, T. Yokozawa, J. H. Lee, Y. S. Kim, and J. S. Choi, “Anti-Alzheimer and antioxidant activities of coptidis rhizoma alkaloids,” Biological and Pharmaceutical Bulletin, vol. 32, no. 8, pp. 1433–1438, 2009.

33. Priyadarsini K.I. The chemistry of curcumin: From extraction to therapeutic agent. Molecules. 2014; 19:20091–20112. doe: 10.3390/molecules191220091.

34. Gupta S.C., Patchva S., Aggarwal B.B. Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials. AAPS J. 2013; 15:195–218. doe: 10.1208/s12248-012-9432-8.

35. Aggarwal B.B., Kumar A., Bharti A.C. Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Res. 2003; 23:363–398.

36. Lestari M.L., Indrayanto G. Curcumin. Profiles Drug Subst. Excip. Relat. Methodol. 2014; 39:113–204.

37. Mahady G.B., Pendland S.L., Yun G., Lu Z.Z. Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen. Anticancer Res. 2002; 22:4179–4181.

38. Mishra S, Palanivelu K (2008), The effect of curcumin (turmeric) on Alzheimer’s disease: An overview. Ann Indian Acad Neurol 11(1): 13-19.

39. Aggarwal B, Harikumar K (2009) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Inter J Biochem Cell Biol 41:40-59.

40. Tang Y (2003) Genetic studies in Alzheimer’s disease. Dialogues Clan Neuroscience 5:17-26.

41. Reinke A, Gestwicki J (2007) Structure-activity relationships of amyloidbeta-aggregation inhibitors based on curcumin: influence of link length and flexibility. Chem Biolo Drug Des 70:206-215.

42. Kumar GP, Khanum F (2012) Neuroprotective potential of phytochemicals. Pharmacognacy Rev 6(12): 81-90.

43. Arteaga O, Revuelta M, Urigüen L, Álvarez A, Montalvo H, et al. (2015) Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats. Plos One 10(11): e0142424.

44. Kim J, Lee HJ, Lee KW. Naturally occurring phytochemicals for the prevention of Alzheimer’s disease. J Neurochem.2010; 112:1415-1430.

45. Rajakrishnan V, Viswanathan P, Rajasekharan KN, Menon VP. Neuroprotective role of curcumin from Curcuma longa on ethanol-induced brain damage. Phytother Research. 1999; 13:571-574.

46. Agrawal R, Mishra B, Tyagi E, Nath C, Shukla R. Effect of curcumin on brain insulin receptors and memory functions in STZ induced dementia model of rat. Pharmacol Res. 2010; 61:247-252.

47. Walesiuk A, Braszko JJ (2009) Preventive action of Ginkgo biloba in stress- and corticosterone-induced impairment of spatial memory in rats. Phytomedicine 16:40-46.

48. Nalini K, Aroor A, Karanth K, Rao A (1992) Centella asiatica fresh leaf aqueous extract on learning and memory and biogenic amine turnover in albino rats. Fitoterapia 63:232-233.

49. Godkar PB, Gordon RK, Ravindran A, Doctor BP (2006) Celastrus paniculatus seed oil and organic extracts attenuate hydrogen peroxide and glutamate-induced injury in embryonic rat forebrain neuronal cells. Phytomedicine 13:29-36.

50. Godkar P, Gordon R, Ravindran A (2003) Celastrus paniculatus seed water soluble extracts protect cultured rat forebrain neuronal cells from hydrogen peroxide-induced oxidative injury. Fitoterapia 74:658-669.

51. Katekhaye S, Duggal S, Singh A (2011) an inside preview of nutritional and pharmacological profile of Celastrus paniculatus. Int J Recent Advanced Pharm Research 1:19-24.

Received on 11.06.2019 Modified on 04.07.2019

Research J. Pharm. and Tech. 2020; 13(1): 475-480.

DOI: 10.5958/0974-360X.2020.00092.X