Flavonoids, Phenolics and Acetylcholinesterase Inhibitory Potential of Different Solvent Extracts of some Medicinal Plants used as Brain Tonics: A Comparative Study

Document Type : Research Paper


Department of Chemistry, Forman Christian College (A Chartered University), Lahore 54000, Pakistan


Alzheimer’s disease (AD) is a common old-age ailment characterized by the loss of memory and impairment of cognitive abilities and associated with an overexpression of cholinesterase enzymes. Quest for effective, safe and affordable inhibitors of these enzymes is thus required. The present project was designed to explore natural bioactive compounds with the ability to act as acetylcholinesterase (AChE) inhibitors. AChE inhibitory activity of methanolic (ME), ethyl acetate (EAE), acetonic (AE) and hydroethanolic (HEE) extracts of common medicinal plants used in brain tonics were estimated. Total phenolic and flavonoid contents of the extracts have also been determined. The plants studied included Borago officinalis L., Salvia haematodes Scop., Matthiola incana (L.) R.Br., Moringa oleifera Lam., Lallemantia royleana (Benth.) Benth., Lavandula stoechas L., Centaurea behen DC. and Coriandrum sativum L. The MEs of all the selected plants showed the highest activity except M. oleifera and S. haematodes whose activity was slightly less than EAE of M. oleifera and AE of S. haematodes. EAEs of B. officinalis, M. oleifera and S. haematodes and AEs of B. officinalis and S. haematodes were also notable. A moderate correlation was found between TPC and AChE inhibitory activity of MEs and a moderately high correlation was found between TPC and AChE inhibitory activity of AEs of the selected plants. The acetylcholinesterase inhibition might play a role in the brain tonic effect of the selected plants. The activity may at least partly be rendered by the phenolic compounds present in the plants.


  1. Davies P, Maloney A.J. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet. 1976;2:1403.
  2. Kim J, Lee HJ, Lee KW. Naturally occurring phytochemicals for the prevention of Alzheimer's disease. J Neurochem. 2010;112:1415-1430.
  3. Bartus R.T, Dean R.L, Beer B, Lippa A.S. The cholinergic hypothesis of geriatric memory dysfunction. Science. 1982;217:408-414.
  4. Holland D, Desikan RS, Dale AM, McEvoy LK. Alzheimer's Disease Neuroimaging I. Rates of decline in Alzheimer disease decrease with age. PLoS One. 2012;7:42325.
  5. Roseiroa LB, Rauterb AP, Serralheirob MLM. Polyphenols as acetylcholinesterase inhibitors: structural specificity and impact on human disease. Nutrition and Aging. 2012;1:99-111.
  6. Oh MH, Houghton P.J, Whang W.K, Cho JH. Screening of Korean herbal medicines used to improve cognitive function for anti-cholinesterase activity. Phytomedicine. 2004;11:544-548.
  7. Ingkaninan K, Temkitthawon P, Chuenchom K, Yuyaem T, Thongnoi W. Screening for acetylcholinesterase inhibitory activity in plants used in Thai traditional rejuvenating and neurotonic remedies. J Ethnopharmacol. 2003;89:261-264.
  8. Adsersen A.B, Gauguin L, Gudiksen A.K. Screening of plants used in Danish folk medicine to treat memory dysfunction for acetylcholinesterase inhibitory activity. J Ethnopharmacol. 2006;104:418-422.
  9. Howes MJ, Houghton P.J. Plants used in Chinese and Indian traditional medicine for improvement of memory and cognitive function. Pharmacol Biochem Behav. 2003;75:513-527.
  10. Mukherjee P.K, Kumar V, Mal M, Houghton P.J. Acetylcholinesterase inhibitors from plants. Phytomedicine. 2007;14:289-300.
  11. Perry1 E, Howes M.R. Medicinal plants and dementia therapy: herbal hopes for brain aging? CNS Neurosci Ther. 2011;17:683-698.
  12. Katalini M, Bosak A, Kovarik Z. Flavonoids as inhibitors of human BChE. Food Technol Biotechnol. 2014;52:64-67.
  13. Pueyo U, Calvo MI. Flavonoids as acetylcholinesterase inhibitors Curr Med Chem. 2011;18:5289-5302.
  14. Ebrahimi A, Schluesener H. Natural polyphenols against neurodegenerative disorders: Potentials and pitfalls. Ageing Res Rev. 2012;11:329-345.
  15. Molino S, Dossena M, Buonocore D, Ferrari F,  Venturini L, Ricevuti G,   Verri M. Polyphenols in dementia: From molecular basis to clinical trials. Life Sci. 2016;161:69-77.
  16. Williams R.J, Spencer J.P.E. Flavonoids, cognition, and dementia: Actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radic Biol Med. 2012;52:35-45.
  17. Obuleso M, Rao D.M. Effect of plant extracts on Alzheimer's disease: An insight into therapeutic avenues. J Neurosci Rural Pract. 2011;2:56-61.
  18. Upadhyay A, Singh V.K, Singh D.K. Characterization of Molluscicidal components of Moringa oleifera leaf and Momordica charantia fruits and their modes of action in snail Lymnaea acuminate. J Inst Trop Med Sao Paulo. 2013;55:251-259.
  19. Rizwan A, Saeed R, Ahmad T, Ullah A, Ather Z, Muhammad S, Hussain I, Ali U. Evaluation of Salvia haematodes Linn for their anti-oxidant, anti-microbial, anti-lipoxygenase and anti-cholinesterase activity. J Phytopharmacology. 2014;3:316-320.
  20. Sharayu R, Asmita M. Screening of Acetylcholinesterase inhibitors by Moringa Olifera. Int J Life Sci. 2016;4:302-305.
  21. Shawwal M, Badruddeen, Khushtar M, Rahman M.A. Protective effect of hydro-alcoholic extract of Salvia haematodes Wall root on cognitive functions in scopolamine-induces amnesia in rats. J Tradit Complement Med. 2017;7:471-475.
  22. Mathew M, Subramanian S. In vitro screening for anti-cholinesterase and antioxidant activity of methanolic extracts of ayurvedic medicinal plants used for cognitive disorders. The Plos One. 2014. doi: 10.1371/journal.pone.0086804.
  23. Howes MJ. Houghton PJ. Plants used in Chinese and Indian traditional medicine for improvement of memory and cognitive function. Pharmacol Biochem Behav. 2003;75:513-527.
  24. Ahmed D, Fatima K, Saeed R. Analysis of phenolic and flavonoid contents, and the anti-oxidative potential and lipid peroxidation inhibitory activity of methanolic extract of Carissa opaca roots and its fractions in different solvents. Antioxidants. 2014;3:671-683.
  25. Slinkard K, Singleton V.L. Total phenol analysis: Automation and comparison with manual methods. Am J Enol Vitic. 1977;28:49-55.
  26. Ellman G, Courtney D, Andres V. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7:88-95.
  27. Gocer H, Topal F, Topal M, Küçük M, Teke D, Gülçin I, Alwasel SH, Supuran CT. Acetylcholinesterase and carbonic anhydrase isoenzymes I and II inhibition profiles of taxifolin. J Enzyme Inhib Med Chem. 2016;31:441-447.
  28. Pandey A, Tripathi S. Concept of standardization, extraction and pre phytochemical screening strategies for herbal drug. J Pharmacogn Phytochem. 2014;2:115-119.
  29. Chengxuan Q, Kivipelto M, Eva VS. Epidemiology of Alzheimer’s disease: occurrence, determinants, and strategies toward intervention. Dialogues Clin Neurosci. 2009;11:111-128.
  30. Anonymous, Alzheimer's Association, Alzheimer's disease facts and figures. Alzheimer's & Dementia. 2018;14:367-429.
  31. Dhawan D, Gupta J. Comparison of different solvents for phytochemical extraction potential from Datura metel plant leaves. Int J Biol Chem. 2017;11:17-22.
  32. Moon CS. Estimations of the lethal and exposure doses for representative methanol symptoms in humans. Ann Occup Environ Med. 2017;29:44.
  33. Polumackanycz M, Sledzinski T, Goyke E, Wesolowski M, Viapiana A. A comparative study on the phenolic composition and biological activities of Morus alba L. commercial samples. Molecules. 2019;24:3082.
  34. Truong D.H, Nguyen D.H, Ta N.T.A, Bui AV, Do T.H. Evaluation of the use of different solvents for phytochemical constituents, antioxidants, and in vitro anti-inflammatory activities of Severinia buxifolia. J. Food Qual. 2019.
  35. Do QD, Angkawijaya A.E, Tran-Nguyen P.L, Huynh L.H, Soetaredjo FE, Ismadji S, Ju YH. Effect of extraction solvent on total phenol content, total flavonoid content, and antioxidant activity of Limnophila aromatica. J Food Drug Anal. 2014;22:296-302.