The Potential of Herbal Plants and Bioactive β Sitosterol in Circumventing Alzheimer’s Disease – A Review

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Authors

  • Apoorva Mishra
     Department of Pharmacology, Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida - 201306, Uttar Pradesh ,IN
  • Saumya Das
     Department of Pharmacology, Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida - 201306, Uttar Pradesh ,IN
  • Soni Kumari
     Department of Pharmacology, Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida - 201306, Uttar Pradesh ,IN
  • Anmol Kanda
     Department of Pharmacology, Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida - 201306, Uttar Pradesh ,IN
  • Vishnu Prabhakar
     Department of Pharmacology, Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida - 201306, Uttar Pradesh ,IN

DOI:

https://doi.org/10.18311/jnr/2023/32973

Keywords:

Acetylcholinesterase, Antioxidants, β Amyloid, Free Radicals, Herbal Plants, Lipid Peroxidation, Neurodegeneration, β Sitosterol, γ Secretase

Abstract

Alzheimer’s Disease (AD), a neurological ailment, mostly affects the older population all around the world. Rational therapies show limited efficacy, adverse effects, and poor patient compliance therefore herbal drugs are considered as a suitable supplementation to the drug therapy for the treatment of AD. According to research, herbal drugs reduce symptoms of AD and also improve brain functioning by the inhibition of β amyloid, γ-secretase, and acetylcholine along with the regulation of antioxidants and the activation of α-secretase. Various herbal plants like Salvia officinalis, Bertholletia excelsa, Withania somnifera and Urtica dioica help in slowing down the progression of AD by scavenging the free radicals, inhibiting of lipid peroxidation, β amyloid, and tau phosphorylation. β sitosterol, a phytosterol found abundantly in plants has the ability to cross the Blood Brain Barrier and thus acts as a bioactive constituent in circumventing various neurological disorders. Numerous in vitro and in vivo investigations indicate that β sitosterol shows immunomodulatory, lipid-lowering as well as antioxidant properties. The plant sterol, β sitosterol has the capacity to decrease β amyloid platelet synthesis, indicating that it might be helpful in the treatment of prevention of AD. Treatment with β sitosterol can lessen plaque burden and also enhance spatial learning and recognition ability in patients suffering from AD.

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Published

2023-07-03

How to Cite

Mishra, A., Das, S., Kumari, S., Kanda, A., & Prabhakar, V. (2023). The Potential of Herbal Plants and Bioactive β Sitosterol in Circumventing Alzheimer’s Disease – A Review. Journal of Natural Remedies, 23(3), 727–745. https://doi.org/10.18311/jnr/2023/32973

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Volume 23 Issue 3 July 2023

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Review Articles

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Copyright (c) 2022 Apoorva Mishra, Saumya Das, Soni Kumari, Anmol Kanda, Vishnu Prabhakar (Author)

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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Received 2023-02-09
Accepted 2023-04-24
Published 2023-07-03

 

References

Jacquemont T, De Vico Fallani F, Bertrand A, Epelbaum S, Routier A, Dubois B, et al. Amyloidosis and neurodegeneration result in distinct structural connectivity patterns in mild cognitive impairment. Neurobiol Aging. 2017; 55:177- 89. PMID 28457579. https://doi.org/10.1016/j. neurobiolaging.2017.03.023 DOI: https://doi.org/10.1016/j.neurobiolaging.2017.03.023

Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012; 148(6):1204- 22. PMID 22424230. https://doi.org/10.1016/j. cell.2012.02.040 DOI: https://doi.org/10.1016/j.cell.2012.02.040

Więckowska A, Kołaczkowski M, Bucki A, Godyń J, Marcinkowska M, Więckowski K, et al. Novel multi-target-directed ligands for Alzheimer’s disease: combining cholinesterase inhibitors and 5-HT6 receptor antagonists. Design, synthesis, and biological evaluation. Eur J Med Chem. 2016; 124:63- 81. PMID 27560283. https://doi.org/10.1016/j. ejmech.2016.08.016 DOI: https://doi.org/10.1016/j.ejmech.2016.08.016

Aprahamian I, Stella F, Forlenza OV. New treatment strategies for Alzheimer’s disease: Is there hope? Indian J Med Res. 2013; 138(4):449-60. PMID 24434253.

Ma SL, Pastorino L, Zhou XZ, Lu KP. Prolyl isomerase Pin1 promotes Amyloid Precursor Protein (APP) turnover by inhibiting Glycogen Synthase Kinase-3β (GSK3β) activity: A novel mechanism for Pin1 to protect against Alzheimer’s disease. J Biol Chem. 2012; 287(10):6969-73. PMID 22184106. https://doi. org/10.1074/jbc.C111.298596 DOI: https://doi.org/10.1074/jbc.C111.298596

Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol. 2011; 10(9):819-28. PMID 21775213. https://doi.org/10.1016/S1474-4422(11)70072-2 DOI: https://doi.org/10.1016/S1474-4422(11)70072-2

Bateman RJ. Amyloid-beta production and clearance rates in Alzheimer’s disease. J Alzheimers Assoc. 2010; 6(4):S101. https://doi.org/10.1016/j. jalz.2010.05.318 DOI: https://doi.org/10.1016/j.jalz.2010.05.318

Guerreiro R, Bras J. The age factor in Alzheimer’s disease. Genome Med. 2015; 7(1):106. PMID 26482651. https://doi.org/10.1186/s13073-015-0232-5 DOI: https://doi.org/10.1186/s13073-015-0232-5

Perrig WJ, Perrig P, Stähelin HB. The relation between antioxidants and memory performance in the old and very old. J Am Geriatr Soc. 1997; 45(6):718-24. PMID 9180666. https://doi. org/10.1111/j.1532-5415.1997.tb01476.x DOI: https://doi.org/10.1111/j.1532-5415.1997.tb01476.x

Berr C. Cognitive impairment and oxidative stress in the elderly: results of epidemiological studies. BioFactors. 2000; 13(1-4):205-9. PMID 11237183. https://doi.org/10.1002/biof.5520130132 DOI: https://doi.org/10.1002/biof.5520130132

Ravi KS, Narasingappa Ramesh B, Shilpa Kj, Poyya J, Karanth J, Raju NG, Joshi CG. Neuroprotective role of herbal alternatives in circumventing Alzheimer’s disease through multi-targeting approach-a review. Egyptian Journal of Basic and Applied Sciences. 2022; 9(1):91-124. https://doi.org/10.1080/23148 08X.2021.2021749 DOI: https://doi.org/10.1080/2314808X.2021.2021749

Zhang LH, Wang X, Stoltenberg M, Danscher G, Huang L, Wang ZY. Abundant expression of zinc transporters in the amyloid plaques of Alzheimer’s disease brain. Brain Res Bull. 2008; 77(1):55- 60. PMID 18639746. https://doi.org/10.1016/j. brainresbull.2008.03.014 DOI: https://doi.org/10.1016/j.brainresbull.2008.03.014

Ayaz M, Junaid M, Ullah F, Subhan F, Sadiq A, Ali G, et al. Anti-Alzheimer’s studies on β-sitosterol isolated from Polygonum hydropiper L. Front Pharmacol. 2017; 8:697. PMID 29056913. https:// doi.org/10.3389/fphar.2017.00697

Gómez-Isla T, Price JL, McKeel Jr DW, Morris JC, Growdon JH, Hyman BT. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer’s disease. J Neurosci. 1996; 16(14):4491- 500. PMID 8699259. https://doi.org/10.1523/ JNEUROSCI.16-14-04491.1996 DOI: https://doi.org/10.1523/JNEUROSCI.16-14-04491.1996

Palop JJ, Chin J, Mucke L. A network dysfunction perspective on neurodegenerative diseases. Nature. 2006; 443(7113):768-73. PMID 17051202. https:// doi.org/10.1038/nature05289 DOI: https://doi.org/10.1038/nature05289

Bertram L, Lill CM, Tanzi RE. The genetics of Alzheimer’s disease: back to the future. Neuron. 2010; 68(2):270-81. PMID 20955934. https://doi. org/10.1016/j.neuron.2010.10.013 DOI: https://doi.org/10.1016/j.neuron.2010.10.013

Reitz C, Brayne C, Mayeux R. Epidemiology of Alzheimer’s disease. Nat Rev Neurol. 2011; 7(3):137- 52. PMID 21304480. https://doi.org/10.1038/ nrneurol.2011.2 DOI: https://doi.org/10.1038/nrneurol.2011.2

Sayre LM, Zelasko DA, Harris PL, Perry G, Salomon RG, Smith MA. 4hydroxynonenal‐derived advanced lipid peroxidation end products are increased in Alzheimer’s disease. J Neurochem. 1997; 68(5):2092-7. PMID 9109537. https://doi. org/10.1046/j.1471-4159.1997.68052092.x

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(8):1594- 601. PMID 7644059. https://doi.org/10.1212/ WNL.45.8.1594 DOI: https://doi.org/10.1212/WNL.45.8.1594

Singhal A, Bangar O, Naithani V. Medicinal plants with a potential to treat Alzheimer’s and associated symptoms. Int J Nutr Pharmacol Neurol Dis. 2012; 2(2):84. https://doi.org/10.4103/2231-0738.95927

Smith MA, Taneda S, Richey PL, Miyata S, Yan SD, Stern D, et al. Advanced Maillard reaction end products are associated with Alzheimer’s disease pathology. Proc Natl Acad Sci U S A. 1994; 91(12):5710-4. PMID 8202552. https://doi. org/10.1073/pnas.91.12.5710 DOI: https://doi.org/10.1073/pnas.91.12.5710

Gsell W, Conrad R, Hickethier M, Sofic E, Frölich L, Wichart I, et al. Decreased catalase activity but unchanged superoxide dismutase activity in brains of patients with dementia of Alzheimer type. J Neurochem. 1995; 64(3): 1216-23. PMID 7861154. https://doi.org/10.1046/ j.1471-4159.1995.64031216.x DOI: https://doi.org/10.1046/j.1471-4159.1995.64031216.x

Smith MA, Richey Harris PLR, Sayre LM, Beckman JS, Perry G. Widespread peroxynitrite-mediated damage in Alzheimer’s disease. J Neurosci. 1997; 17(8):2653-7. PMID 9092586. https://doi. org/10.1523/JNEUROSCI.17-08-02653.1997 DOI: https://doi.org/10.1523/JNEUROSCI.17-08-02653.1997

Gabbita SP, Lovell MA, Markesbery WR. Increased nuclear DNA oxidation in the brain in Alzheimer’s disease. J Neurochem. 1998; 71(5):2034-40. PMID 9798928. https://doi. org/10.1046/j.1471-4159.1998.71052034.x DOI: https://doi.org/10.1046/j.1471-4159.1998.71052034.x

Montine TJ, Amarnath V, Martin ME, Strittmatter WJ, Graham DG. E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19 neuroglial cultures. Am J Pathol. 1996; 148(1):89- 93. PMID 8546230.

Sayre LM, Zelasko DA, Harris PL, Perry G, Salomon RG, Smith MA. 4-hydroxynonenal-derived advanced lipid peroxidation end products are increased in Alzheimer’s disease. J Neurochem. 1997; 68(5):2092-7. PMID 9109537. https://doi. org/10.1046/j.1471-4159.1997.68052092.x DOI: https://doi.org/10.1046/j.1471-4159.1997.68052092.x

Smith CD, Carney JM, Starke-Reed PE, Oliver CN, Stadtman ER, Floyd RA, et al. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci U S A. 1991; 88(23):10540-3. PMID 1683703. https://doi. org/10.1073/pnas.88.23.10540 DOI: https://doi.org/10.1073/pnas.88.23.10540

Collins AR, Dusinská M, Gedik CM, Stĕtina R. Oxidative damage to DNA: do we have a reliable biomarker? Environ Health Perspect. 1996; 104(3):465-9. PMID 8781365. https://doi. org/10.1289/ehp.96104s3465 DOI: https://doi.org/10.1289/ehp.96104s3465

Smith MA, Rudnicka-Nawrot M, Richey PL, Praprotnik D, Mulvihill P, Miller CA, et al. Carbonyl-related posttranslational modification of neurofilament protein in the neurofibrillary pathology of Alzheimer’s disease. J Neurochem. 1995; 64(6):2660-6. PMID 7539057. https://doi. org/10.1046/j.1471-4159.1995.64062660.x DOI: https://doi.org/10.1046/j.1471-4159.1995.64062660.x

Smith MA, Sayre LM, Monnier VM, Perry G. Radical AGEing in Alzheimer’s disease. Trends Neurosci. 1995; 18(4):172-6. PMID 7778188. https://doi. org/10.1016/0166-2236(95)93897-7 DOI: https://doi.org/10.1016/0166-2236(95)93897-7

Sharma R, Kuca K, Nepovimova E, Kabra A, Rao MM, Prajapati PK. Traditional Ayurvedic and herbal remedies for Alzheimer’s disease: from bench to bedside. Expert Rev Neurotherapeutics. 2019; 19(5):359-74. PMID 30884983. https://doi.org/10.1 080/14737175.2019.1596803 DOI: https://doi.org/10.1080/14737175.2019.1596803

Ye JY, Li L, Hao QM, Qin Y, Ma CS. β-sitosterol treatment attenuates cognitive deficits and prevents amyloid plaque deposition in amyloid protein precursor/presenilin 1 mice. Korean J Physiol Pharmacol. 2020; 24(1):39-46. PMID 31908573. https://doi.org/10.4196/kjpp.2020.24.1.39 DOI: https://doi.org/10.4196/kjpp.2020.24.1.39

Akhondzadeh S, Abbasi SH. Herbal medicine in the treatment of Alzheimer’s disease. Am J Alzheimers Dis Other Demen. 2006; 21(2):113-8. PMID 16634467. https://doi.org/10.1177/153331750602100211 DOI: https://doi.org/10.1177/153331750602100211

Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007; 70(3):461-77. PMID 17309302. https:// doi.org/10.1021/np068054v DOI: https://doi.org/10.1021/np068054v

Abascal K, Yarnell E. Alzheimer’s disease: Part 2-A botanical treatment plan. Altern Complement Ther. 2004; 10(2):67-72. https://doi. org/10.1089/107628004773933299 DOI: https://doi.org/10.1089/107628004773933299

Rasoanaivo P, Wright CW, Willcox ML, Gilbert B. Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions. Malar J. 2011; 10(1):S4. PMID 21411015. https://doi.org/10.1186/1475-2875-10- S1-S4 DOI: https://doi.org/10.1186/1475-2875-10-S1-S4

Howes MJ, Houghton PJ. Plants are used in Chinese and Indian traditional medicine for the improvement of memory and cognitive function. Pharmacol Biochem Behav. 2003; 75(3):513-27. PMID 12895669. https://doi.org/10.1016/S0091- 3057(03)00128-X DOI: https://doi.org/10.1016/S0091-3057(03)00128-X

Smith JV, Luo Y. Studies on molecular mechanisms of Ginkgo biloba extract. Appl Microbiol Biotechnol. 2004; 64(4):465-72. PMID 14740187. https://doi. org/10.1007/s00253-003-1527-9 DOI: https://doi.org/10.1007/s00253-003-1527-9

Ramassamy C, Longpré F, Christen Y. Ginkgo biloba extract (EGb 761) in Alzheimer’s disease: is there any evidence? Curr Alzheimer Res. 2007; 4(3):253-62. PMID 17627482. https://doi. org/10.2174/156720507781077304 DOI: https://doi.org/10.2174/156720507781077304

Mahadevan S, Park Y. Multifaceted therapeutic benefits of Ginkgo biloba L.: Chemistry, efficacy, safety, and uses. J Food Sci. 2008; 73(1):R14-9. PMID 18211362. https://doi.org/10.1111/j.1750-3841.2007.00597.x DOI: https://doi.org/10.1111/j.1750-3841.2007.00597.x

Singhal A, Bangar O, Naithani V. Medicinal plants with a potential to treat Alzheimer’s and associated symptoms. Int J Nutr Pharmacol Neurol Dis. 2012; 2(2):84. https://doi.org/10.4103/2231-0738.95927 DOI: https://doi.org/10.4103/2231-0738.95927

Howes MR, Fang R, Houghton PJ. Effect of Chinese herbal medicine on Alzheimer’s disease. Int Rev Neurobiol. 2017; 135:29-56. PMID 28807163. https://doi.org/10.1016/bs.irn.2017.02.003 DOI: https://doi.org/10.1016/bs.irn.2017.02.003

Bihaqi SW, Singh AP, Tiwari M. Supplementation of Convolvulus pluricaulis attenuates scopolamine-induced Increased Tau and Amyloid Precursor Protein (AβPP) Expression in Rat Brain. Indian J Pharmacol. 2012; 44(5):593-8. PMID 23112420. https://doi.org/10.4103/0253-7613.100383 DOI: https://doi.org/10.4103/0253-7613.100383

Dubey A, Ghosh NS, Agnihotri N, Kumar A, Pandey M, Nishad S. Herbs-derived bioactive compounds and their potential for the treatment of neurological disorders. Clin Schizophr Relat Psychoses. 2022; 16(2).

Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: The Indian solid gold in the molecular targets and therapeutic uses of curcumin in health and disease. 2007; 1-75. PMID 17569205. https:// doi.org/10.1007/978-0-387-46401-5_1 DOI: https://doi.org/10.1007/978-0-387-46401-5_1

Breitner JC, Welsh KA, Helms MJ, Gaskell PC, Gau BA, Roses AD, et al. Delayed onset of Alzheimer’s disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs. Neurobiol Aging. 1995; 16(4):523-30. PMID 8544901. https://doi. org/10.1016/0197-4580(95)00049-K DOI: https://doi.org/10.1016/0197-4580(95)00049-K

Begum AN, Jones MR, Lim GP, Morihara T, Kim P, Heath DD, et al. Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer’s disease. J Pharmacol Exp Ther. 2008; 326(1):196-208. PMID 18417733. https://doi.org/10.1124/jpet.108.137455 DOI: https://doi.org/10.1124/jpet.108.137455

Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001; 21(21):8370- 7. PMID 11606625. https://doi.org/10.1523/ JNEUROSCI.21-21-08370.2001 DOI: https://doi.org/10.1523/JNEUROSCI.21-21-08370.2001

Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, et al. Curcumin inhibits the formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005; 280(7):5892-901. PMID 15590663. https://doi. org/10.1074/jbc.M404751200 DOI: https://doi.org/10.1074/jbc.M404751200

Zatta P, Drago D, Bolognin S, Sensi SL. Alzheimer’s disease, metal ions, and metal homeostatic therapy. Trends Pharmacol Sci. 2009; 30(7):346-55. PMID 19540003. https://doi.org/10.1016/j.tips.2009.05.002 DOI: https://doi.org/10.1016/j.tips.2009.05.002

Cristóvão JS, Santos R, Gomes CM. Metals and neuronal metal binding proteins implicated in Alzheimer’s disease. Oxid Med Cell Longev. 2016; 2016:9812178. PMID 26881049. https://doi. org/10.1155/2016/9812178 DOI: https://doi.org/10.1155/2016/9812178

Baum L, Ng A. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimers Dis. 2004; 6(4):367-77. discussion 443. PMID 15345806. https://doi.org/10.3233/JAD-2004-6403 DOI: https://doi.org/10.3233/JAD-2004-6403

Yan FS, Sun JL, Xie WH, Shen L, Ji HF. Neuroprotective effects and mechanisms of curcumin-Cu(II) and-Zn(II) complexes systems and their pharmacological implications. Nutrients. 2017; 10(1):28. PMID 29283372. https://doi.org/10.3390/ nu10010028 DOI: https://doi.org/10.3390/nu10010028

Lannert H, Hoyer S. Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats. Behav Neurosci. 1998; 112(5):1199-208. PMID 9829797. https://doi.org/10.1037//0735-7044.112.5.1199 DOI: https://doi.org/10.1037/0735-7044.112.5.1199

Ranpariya VL, Parmar SK, Sheth NR, Chandrashekhar VM. Neuroprotective activity of Matricaria recutita against fluoride-induced stress in rats. Pharm Biol. 2011; 49(7):696-701. PMID 21599496. https://doi. org/10.3109/13880209.2010.540249 DOI: https://doi.org/10.3109/13880209.2010.540249

Reddy N, Rajasekhar R. Tinosphora cordifolia chemical constituents and medicinal properties: A review. Sch. Acad. J Pharmacol. 2015; 4:364-9.

Tao R, Wang CZ, Kong ZW. Antibacterial/antifungal activity and synergistic interactions between polyphenols and other lipids isolated from Ginkgo biloba L. leaves. Molecules. 2013; 18(2):2166- 82. PMID 23434869. https://doi.org/10.3390/ molecules18022166 DOI: https://doi.org/10.3390/molecules18022166

Awasthi M, Singh S, Pandey VP, Dwivedi UN. Alzheimer’s disease: An overview of amyloid beta dependent pathogenesis and its therapeutic implications along with in-silico approaches emphasizing the role of natural products. J Neurol Sci. 2016; 361:256-71. PMID 26810552. https://doi. org/10.1016/j.jns.2016.01.008 DOI: https://doi.org/10.1016/j.jns.2016.01.008

Daneshmand P. Neuroprotective effects of Herbal Extract on rat model of Alzheimer’s disease, Avicemma. J Med Biotechnol. 2016; 8(3):120-5.

Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (Ashwagandha): A review. Altern Med Rev. 2000; 5(4):334-46. PMID 10956379.

Matsuda H, Murakami T, Kishi A, Yoshikawa M. Structures of withanolides I, II, III, IV, V, VI, and VII, new withanolide glycosides, from the roots of Indian Withania somnifera Dunal. and inhibitory activity for tachyphylaxis to clonidine in isolated guinea pig ileum. Bioorg Med Chem. 2001; 9(6):1499-507. https://doi.org/10.1016/S0968-0896(01)00024-4 DOI: https://doi.org/10.1016/S0968-0896(01)00024-4

Russo A, Izzo AA, Cardile V, Borrelli F, Vanella A. Indian medicinal plants as antiradical and DNA cleavage protectors. Phytomedicine. 2001; 8(2):125-32. PMID 11315755. https://doi. org/10.1078/0944-7113-00021 DOI: https://doi.org/10.1078/0944-7113-00021

Gupta GL, Rana AC. Withania somnifera (Ashwagandha): A review. Pharmacogn Rev. 2007; 1(1):129-36.

Rita Cardoso B, Silva Bandeira V, Jacob-Filho W, Franciscato Cozzolino SM. Selenium status in elderly: relation to cognitive decline. J Trace Elem Med Biol. 2014; 28(4):422-6. PMID 25220532. https://doi.org/10.1016/j.jtemb.2014.08.009 DOI: https://doi.org/10.1016/j.jtemb.2014.08.009

Mahomoodally MF, Dursun PD, Venugopala KN. Collinsonia canadensis L. In naturally occurring chemicals against Alzheimer’s disease. Academic Press; 2021; 373-7. https://doi.org/10.1016/B978-0- 12-819212-2.00031-1 DOI: https://doi.org/10.1016/B978-0-12-819212-2.00031-1

Yilmaz A, Boga M, Topcu GÜ. Novel terpenoids with potential anti-alzheimer activity from Nepeta obtusicrena. Records of Natural Products. 2016; 10(5):530.

Suvarna CM, Sriya P, Arshad MD, Pavan K. A review on phytochemical and pharmacological properties of Thespesia populnea. Journal of Drug Delivery and Therapeutics. 2018; 8(4):1-4. https:// doi.org/10.22270/jddt.v8i4.1718 DOI: https://doi.org/10.22270/jddt.v8i4.1718

Balaei-Kahnamoei M, Saeedi M, Rastegari A, Shams Ardekani MR, Akbarzadeh T, Khanavi M. Phytochemical analysis and evaluation of the biological activity of Lawsonia inermis seeds

related to Alzheimer’s disease. Evidence-Based Complementary and Alternative Medicine. 2021; 2021. https://doi.org/10.1155/2021/5965061 DOI: https://doi.org/10.1155/2021/5965061

Ali M, Muhammad S, Shah MR, Khan A, Rashid U, Farooq U, Ullah F, Sadiq A, Ayaz M, Ali M, Ahmad M. Neurologically potent molecules from Crataegus oxyacantha; isolation, anticholinesterase inhibition, and molecular docking. Frontiers in Pharmacology. 2017; 8:327. https://doi.org/10.3389/ fphar.2017.00327 DOI: https://doi.org/10.3389/fphar.2017.00327

Hesam Shahrajabian M, Sun W, Cheng Q. A review of chemical constituents, traditional and modern pharmacology of fig (Ficus carica L.), a super fruit with medical astonishing characteristics. Polish Journal of Agronomy. 2021; 44:22-9.

Jan H, Usman H, Shah M, Zaman G, Mushtaq S, Drouet S, Hano C, Abbasi BH. Phytochemical analysis and versatile in vitro evaluation of antimicrobial, cytotoxic, and enzyme inhibition potential of different extracts of traditionally used Aquilegia pubiflora Wall. Ex Royle. BMC Complementary Medicine and Therapies. 2021; 21(1):1-9. https:// doi.org/10.1186/s12906-021-03333-y DOI: https://doi.org/10.1186/s12906-021-03333-y

Ayaz M, Junaid M, Ullah F, Subhan F, Sadiq A, Ali G, Ovais M, Shahid M, Ahmad A, Wadood A, El-Shazly M. Anti-Alzheimer’s studies on β-sitosterol isolated from Polygonum hydropiper L. Frontiers in pharmacology. 2017; 8:697. https://doi.org/10.3389/ fphar.2017.00697

Maqbool Z, Arshad MS, Ali A, Aziz A, Khalid W, Afzal MF, Bangar SP, Addi M, Hano C, Lorenzo JM. Potential Role of Phytochemical Extract from Saffron in Development of Functional Foods and Protection of Brain-Related Disorders. Oxidative Medicine and Cellular Longevity. 2022; 2022:6480590. https://doi. org/10.1155/2022/6480590 DOI: https://doi.org/10.1155/2022/6480590

Lee YJ, Choi DY, Han SB, Kim YH, Kim KH, Hwang BY, et al. Inhibitory effect of ethanol extract of Magnolia officinalis on memory impairment and amyloidogenesis in a transgenic mouse model of Alzheimer’s disease via regulating β‐secretase activity. Phytother Res. 2012; 26(12):1884-92. PMID 22431473. https://doi.org/10.1002/ptr.4643 DOI: https://doi.org/10.1002/ptr.4643

Sigurdsson S, Gudbjarnason S. Inhibition of acetylcholinesterase by extracts and constituents from Angelica archangelica and Geranium sylvaticum. Z Naturforsch C J Biosci. 2007; 62(9-10):689-93. PMID 18069242. https://doi.org/10.1515/znc-2007- 9-1011 DOI: https://doi.org/10.1515/znc-2007-9-1011

Hassan MA, Balasubramanian R, Masoud AD, Burkan ZE, Sughir A, Kumar RS. Role of medicinal plants in neurodegenerative diseases with specialemphasis on Alzheimer’s. Phytomedicine. 2014; 5(6):454-62.

Akram M, Nawaz A. Effects of medicinal plants on Alzheimer’s disease and memory deficits. Neural Regen Res. 2017; 12(4):660-70. PMID 28553349. https://doi.org/10.4103/1673-5374.205108 DOI: https://doi.org/10.4103/1673-5374.205108

Baskar AA, Al Numair KS, Gabriel Paulraj M, Alsaif MA, Muamar MA, Ignacimuthu S. β-sitosterol prevents lipid peroxidation and improves antioxidant status and histoarchitecture in rats with 1,2-dimethylhydrazine-induced colon cancer. J Med Food. 2012; 15(4):335-43. PMID 22353013. https:// doi.org/10.1089/jmf.2011.1780

Avneet G, Pal SM, Siddhraj SS. A review on herbal Ayurvedic medicinal plants and its association with memory functions. Phytomedicine. 2018; 7(2):162- 6. https://doi.org/10.31254/phyto.2018.7210 DOI: https://doi.org/10.31254/phyto.2018.7210

Baskar AA, Al Numair KS, Gabriel Paulraj M, Alsaif MA, Muamar MA, Ignacimuthu S. β-sitosterol prevents lipid peroxidation and improves antioxidant status and histoarchitecture in rats with 1,2-dimethylhydrazine-induced colon cancer. J Med Food. 2012; 15(4):335-43. PMID 22353013. https:// doi.org/10.1089/jmf.2011.1780 DOI: https://doi.org/10.1089/jmf.2011.1780

Burg VK, Grimm HS, Rothhaar TL, Grösgen S, Hundsdörfer B, Haupenthal VJ, et al. Plant sterols the better cholesterol in Alzheimer’s disease? A mechanistic study. J Neurosci. 2013; 33(41):16072- 87. PMID 24107941. https://doi.org/10.1523/ JNEUROSCI.1506-13.2013 DOI: https://doi.org/10.1523/JNEUROSCI.1506-13.2013

Shi C, Wu F, Zhu XC, Xu J. Incorporation of β-sitosterol into the membrane increases resistance to oxidative stress and lipid peroxidation via estrogen receptor-mediated PI3K/GSK3β signaling. Biochim Biophys Acta. 2013; 1830(3):2538- 44. PMID 23266618. https://doi.org/10.1016/j. bbagen.2012.12.012 DOI: https://doi.org/10.1016/j.bbagen.2012.12.012

Shi C, Wu F, Xu J. Incorporation of β-sitosterol into mitochondrial membrane enhances mitochondrial function by promoting inner mitochondrial membrane fluidity. J Bioenerg Biomembr. 2013; 45(3):301-5. PMID 23225137. https://doi. org/10.1007/s10863-012-9495-3 DOI: https://doi.org/10.1007/s10863-012-9495-3

Wang J, Wu F, Shi C. Substitution of membrane cholesterol with β-sitosterol promotes nonamyloidogenic cleavage of the endogenous amyloid precursor protein. Neuroscience. 2013; 247:227- 33. PMID 23707801. https://doi.org/10. 1016/j.neuroscience.2013.05.022 DOI: https://doi.org/10.1016/j.neuroscience.2013.05.022

Babu S, Jayaraman S. An update on β-sitosterol: A potential herbal nutraceutical for diabetic management. Biomed Pharmacother. 2020; 131: 110702. PMID 32882583. https://doi.org/10.1016/j. biopha.2020.110702 DOI: https://doi.org/10.1016/j.biopha.2020.110702

Shi C, Liu J, Wu F, Zhu X, Yew DT, Xu J. β-sitosterol inhibits high cholesterol-induced platelet β-amyloid release. J Bioenerg Biomembr. 2011; 43(6):691-7. PMID 21969169. https://doi.org/10.1007/s10863- 011-9383-2

Saeidnia S, Manayi A, Gohari AR, Abdollahi M. The story of beta-sitosterol - A review. Eur J Med Plants. 2014; 4(5):590-609. https://doi.org/10.9734/ EJMP/2014/7764 DOI: https://doi.org/10.9734/EJMP/2014/7764

Lee MR. The snowdrop (Galanthus nivalis): from Odysseus to Alzheimer. Proc R Coll Physicians Edinb. 1999; 29(4):349-52. PMID 11624093. https:// doi.org/10.1177/147827159902900417 DOI: https://doi.org/10.1177/147827159902900417

Miura K, Kikuzaki H, Nakatani N. Apianane terpenoids from Salvia officinalis. Phytochemistry. 2001; 58(8):1171-5. PMID 11738402. https://doi. org/10.1016/S0031-9422(01)00341-7 DOI: https://doi.org/10.1016/S0031-9422(01)00341-7

Chandra D, Prasad K. Phytochemicals of Acorus calamus (sweet flag). J Med Plants Stud. 2017; 5(5):277-81.

Lee DG, Lee J, Kim KT, Lee SW, Kim YO, Cho IH, et al. High-performance liquid chromatography analysis of phytosterols in panax ginseng root grown under different conditions. J Ginseng Res. 2018; 42(1):16- 20. https://doi.org/10.1016/j.jgr.2016.10.004 DOI: https://doi.org/10.1016/j.jgr.2016.10.004

Irshad S, Khatoon S. Development of a validated highperformance thin-layer chromatography method for the simultaneous estimation of caffeic acid, ferulic acid, β-sitosterol, and lupeol in Convolvulus pluricaulis choisy and its adulterants/substitutes. JPC J Planar Chromatogr Mod TLC. 2018; 31(6):429-36. https://doi.org/10.1556/1006.2018.31.6.2 DOI: https://doi.org/10.1556/1006.2018.31.6.2

Ahmad A, Misra LN. Isolation of herniarin and other constituents from Matricaria chamomilla flowers. Int J Pharmacogn. 1997; 35(2):121-5. https://doi. org/10.1076/phbi.35.2.121.13280 DOI: https://doi.org/10.1076/phbi.35.2.121.13280

Suman A, Ali M, Alam P. New prenylated isoflavones from the roots of Glycyrrhiza glabra. Chem Nat Compd. 2009; 45(4):487-91. https://doi. org/10.1007/s10600-009-9403-1 DOI: https://doi.org/10.1007/s10600-009-9403-1

Valentová K, Buckiová D, Křen V, Pěknicová J, Ulrichová J, Šimánek V. The in vitro biological activity of Lepidium meyenii extracts. Cell Biol Toxicol. 2006; 22(2):91-9. PMID 16528448. https:// doi.org/10.1007/s10565-006-0033-0 DOI: https://doi.org/10.1007/s10565-006-0033-0

Upendra S, Manju B, Praveen K, Geetanjali R, Neeraj K, Bikram S, et al. Antimutagenic extract from Tinospora cordifolia and its chemical composition. J Med Plants Res. 2010; 4(23):2488-94. https://doi. org/10.5897/JMPR10.346 DOI: https://doi.org/10.5897/JMPR10.346

Chunhieng T, Hafidi A, Pioch D, Brochier J, Didier M. Detailed study of Brazil nut (Bertholletia excelsa) oil micro-compounds: phospholipids, tocopherols, and sterols. J Braz Chem Soc. 2008; 19(7):1374-80. https://doi.org/10.1590/S0103-50532008000700021 DOI: https://doi.org/10.1590/S0103-50532008000700021

Nencu I, Vlase L, Istudor V, Mircea TĂ. Preliminary research regarding Urtica urens L. and Urtica dioica L. Amino Acids. 2015; 63:710-5.

Misra L, Mishra P, Pandey A, Sangwan RS, Sangwan NS, Tuli R. Withanolides from Withania somnifera roots. Phytochemistry. 2008; 69(4):1000- 4. PMID 18061221. https://doi.org/10.1016/j. phytochem.2007.10.024 DOI: https://doi.org/10.1016/j.phytochem.2007.10.024

Malik J, Karan M, Vasisht K. Nootropic, anxiolytic and CNS-depressant studies on different plant sources of shankhpushpi. Pharm Biol. 2011; 49(12):1234-42. PMID 21846173. https://doi. org/10.3109/13880209.2011.584539 DOI: https://doi.org/10.3109/13880209.2011.584539

Balkrishna A, Thakur P, Varshney A. Phytochemical profile, pharmacological attributes and medicinal properties of Convolvulus prostratus - A cognitive enhancer herb for the management of neurodegenerative etiologies. Front Pharmacol. 2020; 11:171. PMID 32194410. https://doi. org/10.3389/fphar.2020.00171 DOI: https://doi.org/10.3389/fphar.2020.00171

Takayasu BS, Martins IR, Garnique AMB, Miyamoto S, Machado-Santelli GM, Uemi M, et al. Biological effects of oxy phytosterol generated by β-sitosterol ozonization. Arch Biochem Biophys. 2020; 696:108654. PMID 33130087. https://doi. org/10.1016/j.abb.2020.108654 DOI: https://doi.org/10.1016/j.abb.2020.108654

Saeed AA, Genové G, Li T, Hülshorst F, Betsholtz C, Björkhem I, et al. Increased flux of the plant sterols campesterol and sitosterol across a disrupted blood-brain barrier. Steroids. 2015; 99(B):183- 8. PMID 25683892. https://doi.org/10.1016/j. steroids.2015.02.005 DOI: https://doi.org/10.1016/j.steroids.2015.02.005

Shi C, Liu J, Wu F, Zhu X, Yew DT, Xu J. β-sitosterol inhibits high cholesterol-induced platelet β-amyloid release. J Bioenerg Biomembr. 2011; 43(6):691-7. PMID 21969169. https://doi.org/10.1007/s10863- 011-9383-2 DOI: https://doi.org/10.1007/s10863-011-9383-2

Butterfield DA, Reed T, Newman SF, Sultana R. Roles of amyloid β-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer’s disease and mild cognitive impairment. Free Radic Biol Med. 2007; 43(5):658- 77. PMID 17664130. https://doi.org/10.1016/j. freeradbiomed.2007.05.037 DOI: https://doi.org/10.1016/j.freeradbiomed.2007.05.037

Babu S, Krishnan M, Rajagopal P, Periyasamy V, Veeraraghavan V, Govindan R, et al. Beta-sitosterol attenuates insulin resistance in adipose tissue via IRS-1/Akt mediated insulin signaling in high-fat diet and sucrose induced type-2 diabetic rats. Eur J Pharmacol. 2020; 873:173004. PMID 32045603. https://doi.org/10.1016/j.ejphar.2020.173004 DOI: https://doi.org/10.1016/j.ejphar.2020.173004

Ayaz M, Junaid M, Ullah F, Subhan F, Sadiq A, Ali G et al. Anti-Alzheimer’s studies on β-sitosterol isolated from Polygonum hydropiper L. Front Pharmacol. 2017; 8:697. PMID 29056913. https:// doi.org/10.3389/fphar.2017.00697 DOI: https://doi.org/10.3389/fphar.2017.00697

Vivancos M, Moreno JJ. β-sitosterol modulates antioxidant enzyme response in RAW 264.7 macrophages. Free Radic Biol Med. 2005; 39(1):91- 7. PMID 15925281. https://doi.org/10.1016/j. freeradbiomed.2005.02.025 DOI: https://doi.org/10.1016/j.freeradbiomed.2005.02.025