Molecular Docking and Cognitive Impairment Attenuating Effect of Phenolic Compound Rich Fraction of Trianthema portulacastrum in Scopolamine Induced Alzheimer’s Disease Like Condition

  • Ekta Yadav
  • Deepika Singh
  • Biplab Debnath
  • Parth Rathee
  • Pankajkumar YadavEmail author
  • Amita VermaEmail author
Original Paper


Dementia is considered as the frequent cause of neurodegenerative mental disorder such as Alzheimer’s disease (AD) amongst elderly people. Free radicals as well as cholinergic deficit neurons within nucleus basalis magnocellularis demonstrated to attribute with aggregation of β amyloid which further acts as an essential hallmark in AD. Various phenolic phytoconstituents exists in Trianthema portulastrum (TP) leaves have been reported as active against various neurological disorders. The current investigation was undertaken to evaluate the antiamnesic potential of butanol fraction of TP hydroethanolic extract (BFTP) by utilizing rodent models of elevated plus maze (EPM) and Hebbs William Maze (HWM) along with in vitro and in vivo antioxidant as well as acetylcholinesterase (AChE) inhibition studies. Molecular docking studies were also performed for evaluation of molecular interaction of existed phenolic compounds in BFTP. In vitro antioxidant study revealed concentration dependant strong ability of BFTP to inhibit free radicals. In vitro AChE inhibition study showed competitive type of inhibition kinetics. BFTP significantly reversed (p < 0.005 versus scopolamine) the damaging effect of scopolamine by reducing TL (Transfer Latency) and TRC (Time taken to recognize the reward chamber) in the EPM and HWM, respectively. BFTP also contributed towards increased (p < 0.005 versus scopolamine) enzymatic antioxidant as well as hippocampal acetylcholine (ACh) levels. Histological studies also supported the results as BFTP pretreated mice significantly reversed the scopolamine induced histological changes in hippocampal region. Docking studies confirmed chlorogenic acid has the most significant binding affinity towards AChE. This research finding concludes that BFTP could be a beneficial agent for management of cognition and behavioral disorders associated with AD.


Learning and memory Alzheimer’s disease Cognitive impairment Oxidative stress Chlorogenic acid Molecular docking 



Authors are grateful to Dr Vikas Kumar, Department of Pharmaceutical Sciences, SHUATS for his generous help in histological studies. Authors extend their thanks to Dr Puhspraj Gupta, Department of Pharmaceutical Sciences, SHUATS for his support during in vivo studies. They also express their gratitude to Prof. R. M. Kadam, Head of Department, Department of Botany, Mahatma Gandhi Mahavidyalaya, Latur, Maharastra, India for his kind help in identification of plant material.


  1. 1.
    Yadav E, Singh D, Yadav P, Verma A (2018) Comparative evaluation of Prosopis cineraria (L.) druce and its ZnO nanoparticles on scopolamine induced amnesia. Front Pharmacol 9:549. CrossRefGoogle Scholar
  2. 2.
    Lee J-S, Kim H-G, Lee H-W et al (2015) Hippocampal memory enhancing activity of pine needle extract against scopolamine-induced amnesia in a mouse model. Sci Rep 5:9651. CrossRefGoogle Scholar
  3. 3.
    Mufson EJ, Counts SE, Perez SE, Ginsberg SD (2008) Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications. Expert Rev Neurother 8:1703–1718. CrossRefGoogle Scholar
  4. 4.
    Dharmarajan TS, Gunturu SG (2009) Alzheimer’s disease: a healthcare burden of epidemic proportion. Am Health Drug Benefits 2:39–47Google Scholar
  5. 5.
    Martin JB (1999) Molecular basis of the neurodegenerative disorders. N Engl J Med 340:1970–1980. CrossRefGoogle Scholar
  6. 6.
    Lee B, Cao R, Choi Y-S et al (2009) The CREB/CRE transcriptional pathway: protection against oxidative stress-mediated neuronal cell death. J Neurochem 108:1251–1265. CrossRefGoogle Scholar
  7. 7.
    Karim N, Khan I, Abdelhalim A et al (2017) Molecular docking and antiamnesic effects of nepitrin isolated from Rosmarinus officinalis on scopolamine-induced memory impairment in mice. Biomed Pharmacother 96:700–709. CrossRefGoogle Scholar
  8. 8.
    Candy JM, Perry RH, Perry EK et al (1983) Pathological changes in the nucleus of Meynert in Alzheimer’s and Parkinson’s diseases. J Neurol Sci 59:277–289CrossRefGoogle Scholar
  9. 9.
    Loizzo MR, Tundis R, Menichini F, Menichini F (2008) Natural products and their derivatives as cholinesterase inhibitors in the treatment of neurodegenerative disorders: an update. Curr Med Chem 15:1209–1228CrossRefGoogle Scholar
  10. 10.
    Husain M, Mehta MA (2011) Cognitive enhancement by drugs in health and disease. Trends Cogn Sci 15:28–36. CrossRefGoogle Scholar
  11. 11.
    Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM (2016) Alzheimer’s disease: targeting the cholinergic system. Curr Neuropharmacol 14:101–115CrossRefGoogle Scholar
  12. 12.
    Williams RJ, Spencer JPE (2012) Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radic Biol Med 52:35–45. CrossRefGoogle Scholar
  13. 13.
    Cho N, Choi JH, Yang H et al (2012) Neuroprotective and anti-inflammatory effects of flavonoids isolated from Rhus verniciflua in neuronal HT22 and microglial BV2 cell lines. Food Chem Toxicol 50:1940–1945. CrossRefGoogle Scholar
  14. 14.
    Yadav E, Singh D, Yadav P, Verma A (2017) Attenuation of dermal wounds via downregulating oxidative stress and inflammatory markers by protocatechuic acid rich n-butanol fraction of Trianthema portulacastrum Linn. in wistar albino rats. Biomed Pharmacother 96:86–97. CrossRefGoogle Scholar
  15. 15.
    Mandal A, Bishayee A (2015) Trianthema portulacastrum Linn. displays anti-inflammatory responses during chemically induced rat mammary tumorigenesis through simultaneous and differential regulation of NF-κB and Nrf2 signaling pathways. Int J Mol Sci 16:2426–2445. CrossRefGoogle Scholar
  16. 16.
    Yamaki J, Nagulapalli Venkata KC, Mandal A et al (2016) Health-promoting and disease-preventive potential of Trianthema portulacastrum Linn. (Gadabani)—an Indian medicinal and dietary plant. J Integr Med 14:84–99. CrossRefGoogle Scholar
  17. 17.
    Sukalingam K, Ganesan K, Xu B (2017) Trianthema portulacastrum L. (giant pigweed): phytochemistry and pharmacological properties. Phytochem Rev 16:461–478. CrossRefGoogle Scholar
  18. 18.
    Re R, Pellegrini N, Proteggente A et al (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 26:1231–1237CrossRefGoogle Scholar
  19. 19.
    Tung BT, Hai NT, Thu DK (2017) Antioxidant and acetylcholinesterase inhibitory activities in vitro of different fraction of Huperzia squarrosa (Forst.) Trevis extract and attenuation of scopolamine-induced cognitive impairment in mice. J Ethnopharmacol 198:24–32. CrossRefGoogle Scholar
  20. 20.
    Sugimoto H, Iimura Y, Yamanishi Y, Yamatsu K (1995) Synthesis and structure-activity relationships of acetylcholinesterase inhibitors: 1-Benzyl-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine hydrochloride and related compounds. J Med Chem 38:4821–4829. CrossRefGoogle Scholar
  21. 21.
    Kamal MA, Greig NH, Alhomida AS, Al-Jafari AA (2000) Kinetics of human acetylcholinesterase inhibition by the novel experimental alzheimer therapeutic agent, tolserine. Biochem Pharmacol 60:561–570. CrossRefGoogle Scholar
  22. 22.
    Itoh J, Nabeshima T, Kameyama T (1990) Utility of an elevated plus-maze for the evaluation of memory in mice: effects of nootropics, scopolamine and electroconvulsive shock. Psychopharmacology 101:27–33. CrossRefGoogle Scholar
  23. 23.
    Mani V, Parle M, Ramasamy K, Abdul Majeed AB (2011) Reversal of memory deficits by Coriandrum sativum leaves in mice. J Sci Food Agric 91:186–192. CrossRefGoogle Scholar
  24. 24.
    Parle M, Bansal N (2011) Antiamnesic activity of an ayurvedic formulation Chyawanprash in mice. Evid Based Complement Alternat Med. Google Scholar
  25. 25.
    Hritcu L, Bagci E, Aydin E, Mihasan M (2015) Antiamnesic and antioxidants effects of Ferulago angulata essential oil against scopolamine-induced memory impairment in laboratory rats. Neurochem Res 40:1799–1809. CrossRefGoogle Scholar
  26. 26.
    Winterbourn CC, Hawkins RE, Brian M, Carrell RW (1975) The estimation of red cell superoxide dismutase activity. J Lab Clin Med 85:337–341Google Scholar
  27. 27.
    Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394. CrossRefGoogle Scholar
  28. 28.
    Sharma M, Gupta YK (2002) Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats. Life Sci 71:2489–2498. CrossRefGoogle Scholar
  29. 29.
    Yagi K (1976) A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med 15:212–216. CrossRefGoogle Scholar
  30. 30.
    Drury R (1983) Theory and practice of histological techniques. J Clin Pathol 36:609. CrossRefGoogle Scholar
  31. 31.
    Muir JL (1997) Acetylcholine, aging, and Alzheimer’s disease. Pharmacol Biochem Behav 56:687–696CrossRefGoogle Scholar
  32. 32.
    Budzynska B, Boguszewska-Czubara A, Kruk-Slomka M et al (2015) Effects of imperatorin on scopolamine-induced cognitive impairment and oxidative stress in mice. Psychopharmacology 232:931–942. CrossRefGoogle Scholar
  33. 33.
    Shivhare MK, Singour PK, Chaurasiya PK, Pawar RS (2012) Trianthema portulacastrum Linn. (Bishkhapra). Pharmacogn Rev 6:132–140. CrossRefGoogle Scholar
  34. 34.
    Sarter M, Bodewitz G, Stephens DN (1988) Attenuation of scopolamine-induced impairment of spontaneous alteration behaviour by antagonist but not inverse agonist and agonist beta-carbolines. Psychopharmacology 94:491–495CrossRefGoogle Scholar
  35. 35.
    Youdim KA, Shukitt-Hale B, Joseph JA (2004) Flavonoids and the brain: interactions at the blood-brain barrier and their physiological effects on the central nervous system. Free Radic Biol Med 37:1683–1693. CrossRefGoogle Scholar
  36. 36.
    Liguori I, Russo G, Curcio F et al (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13:757–772. CrossRefGoogle Scholar
  37. 37.
    Sadiq A, Mahmood F, Ullah F et al (2015) Synthesis, anticholinesterase and antioxidant potentials of ketoesters derivatives of succinimides: a possible role in the management of Alzheimer’s. Chem Cent J. Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Bioorganic & Medicinal Chemistry Research Laboratory, Department of Pharmaceutical SciencesSam Higginbottom University of Agriculture, Technology & Sciences (SHUATS)AllahabadIndia
  2. 2.Bharat TechnologyHowrahIndia
  3. 3.Department of Pharmaceutical Sciences & TechnologyBirla Institute of Technology (BIT), MesraRanchiIndia
  4. 4.Pharmaceuics Laboratory, Department of Pharmaceutical SciencesSam Higginbottom University of Agriculture, Technology & Sciences (SHUATS)AllahabadIndia

Personalised recommendations