Skip to main content

Advertisement

SpringerLink
Log in

A Pharmacological Perspective on Plant-derived Bioactive Molecules for Epilepsy

  • Review
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Epilepsy is a related chronic neurological condition of a predisposition for recurrent epileptic seizures, with various manifestations and causes. Although there are antiepileptic drugs, complementary natural therapies are widely used. The purpose of this systematic review was to analyze the antiepileptic/anticonvulsant pharmacological properties of plant-food derived bioactive molecules. In this regard, a systematic review of the PubMed database was made based on the inclusion criteria. Natural compounds/herbs with scientifically proven antiepileptic properties were selected. Experimental pharmacological studies in vitro and in vivo have shown that flavonoids, alkaloids and terpenoids may have anticonvulsant mechanisms similar to the new generation antiepileptic drugs. The relationships of structure-anticonvulsant effect, pharmacological models, seizure-inducing factors and response, effective dose were also analyzed and discussed. The results of in vitro and in vivo pharmacological studies analyzed in this systematic review support the clinical importance of plant-food-derived bioactive molecules for the complementary treatment of epilepsy. Thus, are opened new perspectives to develop new natural anticonvulsant drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Vyas P, Tulsawani RK, Vohora D (2020) Loss of protection by antiepileptic drugs in lipopolysaccharide-primed pilocarpine-induced status epilepticus is mediated via inflammatory signalling. Neuroscience 442:1–16

    Article  CAS  PubMed  Google Scholar 

  2. Fisher RS et al (2014) ILAE official report: a practical clinical definition of epilepsy. Epilepsia 55(4):475–482

    Article  PubMed  Google Scholar 

  3. Sharifi-Rad J et al (2020) Diet, lifestyle and cardiovascular diseases: linking pathophysiology to cardioprotective effects of natural bioactive compounds. Int J Environ Res Public Health 17(7):2326

    Article  CAS  PubMed Central  Google Scholar 

  4. Salehi B et al (2020) Curcumin’s nanomedicine formulations for therapeutic application in neurological diseases. J Clin Med 9(2):430

    Article  CAS  PubMed Central  Google Scholar 

  5. Kobylarek, D., et al., Advances in the potential biomarkers of epilepsy. Frontiers in Neurology, 2019. 10.

  6. Devinsky O et al (2018) Epilepsy Nat Rev Dis Primers 4:18024

    Article  PubMed  Google Scholar 

  7. Tsatsakis A et al (2019) A mechanistic and pathophysiological approach for stroke associated with drugs of abuse. J Clin Med 8(9):1295

    Article  CAS  PubMed Central  Google Scholar 

  8. Peterman M (1925) The ketogenic diet in epilepsy. J Am Med Assoc 84(26):1979–1983

    Article  Google Scholar 

  9. Barañano KW, Hartman AL (2008) The ketogenic diet: uses in epilepsy and other neurologic illnesses. Curr Treat Options Neurol 10(6):410

    Article  PubMed  PubMed Central  Google Scholar 

  10. Richichi C et al (2004) Anticonvulsant and antiepileptogenic effects mediated by adeno-associated virus vector neuropeptide Y expression in the rat hippocampus. J Neurosci 24(12):3051–3059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Liu W et al (2017) The effects of herbal medicine on epilepsy. Oncotarget 8(29):48385

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sharifi-Rad M et al (2020) Lifestyle, oxidative stress, and antioxidants: back and forth in the pathophysiology of chronic diseases. Front Physiol 11:694–694

    Article  PubMed  PubMed Central  Google Scholar 

  13. Salehi B et al (2020) Avocado-soybean unsaponifiables: a panoply of potentialities to be exploited. Biomolecules 10(1):130

    Article  CAS  PubMed Central  Google Scholar 

  14. Barnes, P.M., et al., Costs of complementary and alternative medicine (CAM) and frequency of visits to CAM practitioners, United States, 2007. 2009.

  15. Salehi B et al (2019) Cucurbits plants: A key emphasis to its pharmacological potential. Molecules 24(10):1854

    Article  CAS  PubMed Central  Google Scholar 

  16. Buenafe OE et al (2013) Tanshinone IIA exhibits anticonvulsant activity in zebrafish and mouse seizure models. ACS Chem Neurosci 4(11):1479–1487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Salehi, B., et al., The Therapeutic Potential of Anthocyanins: Current Approaches Based on Their Molecular Mechanism of Action. 2020.

  18. Rivera D et al (2014) What is in a name? The need for accurate scientific nomenclature for plants. J Ethnopharmacol 152(3):393–402

    Article  PubMed  Google Scholar 

  19. Moher D et al (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8(5):336–341

    Article  PubMed  Google Scholar 

  20. Moshi M, Kagashe G, Mbwambo ZH (2005) Plants used to treat epilepsy by Tanzanian traditional healers. J Ethnopharmacol 97(2):327–336

    Article  PubMed  Google Scholar 

  21. Bum, E.N., et al., Antiepileptic medicinal plants used in traditional medicine to treat epilepsy, in Clinical and Genetic Aspects of Epilepsy. 2011, IntechOpen.

  22. Matuja W, Rwiza H (1994) Knowledge, attitude and practice (KAP) towards epilepsy in secondary school students in Tanzania. Cent Afr J Med 40(1):13–18

    CAS  PubMed  Google Scholar 

  23. Elferink J (1999) Epilepsy and its treatment in the ancient cultures of America. Epilepsia 40(7):1041–1046

    Article  CAS  PubMed  Google Scholar 

  24. Valverde, J.L., The aztec herbal of 1552. Martín de la Cruz'" Libellus de medicinalibus indorum herbis"; context of the sources on nahualt materia medica. Veroffentlichungen der Internationalen Gesellschaft fur Geschichte der Pharmazie e. V, 1984. 53: p. 9–30.

  25. Caulín, A., Historia corográfica, natural y evangélica de la Nueva Andalucia, provincias de Cumaná, Nueva Barcelona, Guayana y vertientes del rio Orinoco. 1841: Reimpresa por G. Corser.

  26. Schachter SC (2009) Botanicals and herbs: a traditional approach to treating epilepsy. Neurotherapeutics 6(2):415–420

    Article  PubMed  PubMed Central  Google Scholar 

  27. Lai CW, Lai YC (1991) History of epilepsy in Chinese traditional medicine. Epilepsia 32(3):299–302

    Article  CAS  PubMed  Google Scholar 

  28. Huard, P. and M. Wong, Chinese medicine. 1968: McGraw-Hill.

  29. Ma R et al (2003) Clinical observation on 930 child epilepsy cases treated with anti-epilepsy capsules. J Tradit Chin Med 23(2):109–112

    PubMed  Google Scholar 

  30. Gorji A, Ghadiri MK (2001) History of epilepsy in Medieval Iranian medicine. Neurosci Biobehav Rev 25(5):455–461

    Article  CAS  PubMed  Google Scholar 

  31. Asadi-Pooya A, Nikseresht A, Yaghoubi E (2012) Old remedies for epilepsy: Avicenna’s medicine. Iran Red Crescent Med J 14(3):174

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Kulabas S et al (2018) Ameliorative potential of Lavandula stoechas in metabolic syndrome via multitarget interactions. J Ethnopharmacol 223:88–98

    Article  CAS  PubMed  Google Scholar 

  33. Abdul-Ghani AS et al (1987) Anticonvulsant effects of some Arab medicinal plants. International Journal of Crude Drug Research 25(1):39–43

    Article  Google Scholar 

  34. Manyam BV (1992) Epilepsy in ancient India. Epilepsia 33(3):473–475

    Article  CAS  PubMed  Google Scholar 

  35. Dash V, Kashyap V (1980) Materia Medica of Ayurveda, vol 1. Concept Publishing, New Delhi

    Google Scholar 

  36. Samhita SPC (1981) Varanas: Text with English translation. Chaukhamba Orientalia, Varanasi

    Google Scholar 

  37. Althoff T et al (2014) X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors. Nature 512(7514):333–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hernandez, C.C. and R.L. Macdonald, A Structural Look at GABAA Receptor Mutations Linked to Epilepsy Syndromes. Brain research, 2019.

  39. Salehi B et al (2019) Epibatidine: A Promising Natural Alkaloid in Health. Biomolecules 9(1):6

    Article  CAS  Google Scholar 

  40. Masiulis S et al (2019) GABA A receptor signalling mechanisms revealed by structural pharmacology. Nature 565(7740):454–459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Elsas SM et al (2010) Passiflora incarnata L. (Passionflower) extracts elicit GABA currents in hippocampal neurons in vitro, and show anxiogenic and anticonvulsant effects in vivo, varying with extraction method. Phytomedicine 17(12):940–949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Singh B, Singh D, Goel RK (2012) Dual protective effect of Passiflora incarnata in epilepsy and associated post-ictal depression. J Ethnopharmacol 139(1):273–279

    Article  PubMed  Google Scholar 

  43. Mishra N et al (2010) Anticonvulsant activity of Benkara malabarica (Linn.) root extract: In vitro and in vivo investigation. J Ethnopharmacol 128(2):533–536

    Article  PubMed  Google Scholar 

  44. Ghasemi M, Schachter SC (2011) The NMDA receptor complex as a therapeutic target in epilepsy: a review. Epilepsy Behav 22(4):617–640

    Article  PubMed  Google Scholar 

  45. Leal MB, de Souza DO, Elisabetsky E (2000) Long-lasting ibogaine protection against NMDA-induced convulsions in mice. Neurochem Res 25(8):1083–1087

    Article  CAS  PubMed  Google Scholar 

  46. Amakhin DV et al (2018) Seizure-induced potentiation of AMPA receptor-mediated synaptic transmission in the entorhinal cortex. Front Cell Neurosci 12:486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lundstrom K, Pham HT, Dinh LD (2017) Interaction of plant extracts with central nervous system receptors. Medicines 4(1):12

    Article  PubMed Central  CAS  Google Scholar 

  48. Sucher NJ, Carles MC (2015) A pharmacological basis of herbal medicines for epilepsy. Epilepsy Behav 52:308–318

    Article  PubMed  Google Scholar 

  49. Powell KL et al (2014) Low threshold T-type calcium channels as targets for novel epilepsy treatments. Br J Clin Pharmacol 77(5):729–739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lin TY et al (2013) Tanshinone IIA, a constituent of Danshen, inhibits the release of glutamate in rat cerebrocortical nerve terminals. J Ethnopharmacol 147(2):488–496

    Article  CAS  PubMed  Google Scholar 

  51. Koenig X et al (2013) Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: a study to assess the drug’s cardiac ion channel profile. Toxicol Appl Pharmacol 273(2):259–268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Lee, J.-H., et al., Effects of Ginsenosides and Their Metabolites on Voltagedependent Ca 2+ Channel Subtypes. Molecules & Cells (Springer Science & Business Media BV), 2006. 21(1).

  53. Tan X-Q et al (2014) Tanshinone II-A sodium sulfonate (DS-201) enhances human BK Ca channel activity by selectively targeting the pore-forming α subunit. Acta Pharmacol Sin 35(11):1351–1363

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Wu S-N et al (2002) Stimulation of the BKCa channel in cultured smooth muscle cells of human trachea by magnolol. Thorax 57(1):67–74

    Article  PubMed  PubMed Central  Google Scholar 

  55. Lilleker JB, Jones MS, Mohanraj R (2013) VGKC complex antibodies in epilepsy: diagnostic yield and therapeutic implications. Seizure 22(9):776–779

    Article  PubMed  Google Scholar 

  56. Kim EJ, Kang D, Han J (2011) Baicalein and wogonin are activators of rat TREK-2 two-pore domain K+ channel. Acta Physiol 202(2):185–192

    Article  CAS  Google Scholar 

  57. Lian, Y.T., et al., Curcumin serves as a human kv1. 3 blocker to inhibit effector memory T lymphocyte activities. Phytotherapy Research, 2013. 27(9): p. 1321–1327.

  58. Kiss T et al (2013) Identification of diterpene alkaloids from Aconitum napellus subsp. firmum and GIRK channel activities of some Aconitum alkaloids. Fitoterapia 90:85–93

    Article  CAS  PubMed  Google Scholar 

  59. Yao Y et al (2010) Quercetin improves cognitive deficits in rats with chronic cerebral ischemia and inhibits voltage-dependent sodium channels in hippocampal CA1 pyramidal neurons. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives 24(1):136–140

    Article  CAS  Google Scholar 

  60. Borcsa B et al (2014) Diterpene alkaloids from the roots of Aconitum moldavicum and assessment of Nav 1.2 sodium channel activity of aconitum alkaloids. Planta Med 80(02/03):231–236

    Article  CAS  PubMed  Google Scholar 

  61. Wang Z-J et al (2014) Identification of both GABAA receptors and voltage-activated Na+ channels as molecular targets of anticonvulsant α-asarone. Front Pharmacol 5:40

    Article  PubMed  PubMed Central  Google Scholar 

  62. Devinsky O et al (2014) Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 55(6):791–802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Khom S et al (2013) GABAA receptor modulation by piperine and a non-TRPV1 activating derivative. Biochem Pharmacol 85(12):1827–1836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Calina D et al (2020) The Treatment of Cognitive, Behavioural and Motor Impairments from Brain Injury and Neurodegenerative Diseases through Cannabinoid System Modulation—Evidence from In Vivo Studies. J Clin Med 9(8):2395

    Article  CAS  PubMed Central  Google Scholar 

  65. Jones NA et al (2010) Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. J Pharmacol Exp Ther 332(2):569–577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Scheau C et al (2020) Cannabinoids in the Pathophysiology of Skin Inflammation. Molecules 25(3):652

    Article  CAS  PubMed Central  Google Scholar 

  67. Diniz TC et al (2015) The role of flavonoids on oxidative stress in epilepsy. Oxid Med Cell Longev 2015:171756

    Article  PubMed  PubMed Central  Google Scholar 

  68. Hanrahan JR, Chebib M, Johnston GAR (2011) Flavonoid modulation of GABAA receptors. Br J Pharmacol 163:234–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Gupta G et al (2012) Sedative, antiepileptic and antipsychotic effects of Viscum album L.(Loranthaceae) in mice and rats. J Ethnopharmacol 141(3):810–816

    Article  CAS  PubMed  Google Scholar 

  70. Singh, P., et al., Antiepileptic activity of aqueous extract of Tricosanthes dioica Roxb. Asian Journal of Plant Science and Research, 2012. 2 p. 45–47

  71. Abbasi E et al (2012) Neuroprotective effects of vitexin, a flavonoid, on pentylenetetrazole-induced seizure in rats. Chem Biol Drug Des 80(2):274–278

    Article  CAS  PubMed  Google Scholar 

  72. Kandhare A, Mukherjee A, Bodhankar S (2018) Anti-epileptic effect of morin against experimental pentylenetetrazol-induced seizures via modulating brain monoamines and oxidative stress. Asian Pac J Trop Biomed 8:352

    Article  Google Scholar 

  73. Mishra A et al (2015) Anticonvulsant mechanisms of piperine, a piperidine alkaloid. Channels 9:317–323

    Article  PubMed  PubMed Central  Google Scholar 

  74. da Cruz GM et al (2013) Piperine decreases pilocarpine-induced convulsions by GABAergic mechanisms. Pharmacol Biochem Behav 104:144–153

    Article  PubMed  CAS  Google Scholar 

  75. Santos Rosa D et al (2012) Erysothrine, an alkaloid extracted from flowers of Erythrina mulungu Mart. ex Benth: evaluating its anticonvulsant and anxiolytic potential. Epilepsy Behav 23(3):205–212

    Article  PubMed  Google Scholar 

  76. Sheng F et al (2016) Protective effects of otophylloside N on pentylenetetrazol-induced neuronal injury in vitro and in vivo. Front Pharmacol 7:224

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Jalsrai A, Grecksch G, Becker A (2010) Evaluation of the effects of Astragalus mongholicus Bunge saponin extract on central nervous system functions. J Ethnopharmacol 131(3):544–549

    Article  CAS  PubMed  Google Scholar 

  78. Sharifi-Rad M et al (2018) Matricaria genus as a source of antimicrobial agents: From farm to pharmacy and food applications. Microbiol Res 215:76–88

    Article  CAS  PubMed  Google Scholar 

  79. Sharifi-Rad, J., et al., Rosmarinus plants: Key farm concepts towards food applications. Phytotherapy Research. n/a(n/a).

  80. Zhu HL et al (2014) Medicinal compounds with antiepileptic/anticonvulsant activities. Epilepsia 55(1):3–16

    Article  CAS  PubMed  Google Scholar 

  81. Salehi B et al (2019) Plant-derived bioactives in oral mucosal lesions: a key emphasis to curcumin, lycopene, chamomile, aloe vera, green tea and coffee properties. Biomolecules 9(3):106

    Article  CAS  PubMed Central  Google Scholar 

  82. Manayi A et al (2016) Natural terpenoids as a promising source for modulation of GABAergic system and treatment of neurological diseases. Pharmacol Rep 68:671–679

    Article  CAS  PubMed  Google Scholar 

  83. Quintans-Júnior LJ et al (2010) Carvacrol, (-)-borneol and citral reduce convulsant activity in rodents. Afr J Biotech 9:6566–6572

    Google Scholar 

  84. Huang CW et al (2012) Characterizing the effects of eugenol on neuronal ionic currents and hyperexcitability. Psychopharmacology 221(4):575–587

    Article  CAS  PubMed  Google Scholar 

  85. Kazmi I et al (2012) Anticonvulsant and depressant-like activity of ursolic acid stearoyl glucoside isolated from Lantana camara L. (Verbanaceae). Asian Pac J Cancer Prev 2:453–456

    Google Scholar 

  86. Bahr TA et al (2019) The effects of various essential oils on epilepsy and acute seizure: a systematic review. Evid Based Complement Alternat Med 2019:6216745

    Article  PubMed  PubMed Central  Google Scholar 

  87. Becker A et al (2014) The anxiolytic effects of a Valerian extract is based on valerenic acid. BMC Complement Altern Med 14(1):267

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Kwon JY et al (2019) Perspective: Therapeutic Potential of Flavonoids as Alternative Medicines in Epilepsy. Adv Nutr 10(5):778–790

    Article  PubMed  PubMed Central  Google Scholar 

  89. Diniz, T.C., et al., The role of flavonoids on oxidative stress in epilepsy. Oxidative medicine and cellular longevity, 2015. 2015.

  90. Xie T et al (2012) Effects of epigallocatechin-3-gallate on pentylenetetrazole-induced kindling, cognitive impairment and oxidative stress in rats. Neurosci Lett 516(2):237–241

    Article  CAS  PubMed  Google Scholar 

  91. Nassiri-Asl M et al (2010) The effects of rutin on the development of pentylenetetrazole kindling and memory retrieval in rats. Epilepsy Behav 18(1–2):50–53

    Article  PubMed  Google Scholar 

  92. Bhutada P et al (2010) Anticonvulsant activity of berberine, an isoquinoline alkaloid in mice. Epilepsy Behav 18(3):207–210

    Article  PubMed  Google Scholar 

  93. Thurner P et al (2014) Mechanism of hERG channel block by the psychoactive indole alkaloid ibogaine. J Pharmacol Exp Ther 348(2):346–358

    Article  PubMed  Google Scholar 

  94. Rafeeq AK, Assad T, Ali M (2017) Anticonvulsant effects of Trigonella foenum-Graecum L. in strychnine induced epilepsy model. J Nutritional Health Food Sci 5:1–6

    Article  Google Scholar 

  95. Das, M.K., P.M. Mazumder, and S. Das, Antiepileptic activity of methanol extract of Butea monosperma (Lam.) Kuntze and its isoalted bioactive compound in experimentally induced convulsion in Swiss Albino mice. Int J Drug Dev & Res, 2016. 8: p. 18–22.

  96. Hosseini A, Mirazi N (2014) Acute administration of ginger (Zingiber officinale rhizomes) extract on timed intravenous pentylenetetrazol infusion seizure model in mice. Epilepsy Res 108(3):411–419

    Article  CAS  PubMed  Google Scholar 

  97. Koutroumanidou E et al (2013) Increased seizure latency and decreased severity of pentylenetetrazol-induced seizures in mice after essential oil administration. Epilepsy Res Treat 2013:532657

    PubMed  PubMed Central  Google Scholar 

  98. Gawande DY et al (2017) Anticonvulsant activity and acute neurotoxic profile of Achyranthes aspera Linn. J Ethnopharmacol 202:97–102

    Article  PubMed  Google Scholar 

  99. Kumar KS et al (2015) Antiepileptic activity of ethanolic extract of Biophytum sensitivum (L.) DC. in animal models. Int. J. Curr. Res. Aca. Rev. 3:23–30

    CAS  Google Scholar 

  100. Chindo BA, Schröder H, Becker A (2015) Methanol extract of Ficus platyphylla ameliorates seizure severity, cognitive deficit and neuronal cell loss in pentylenetetrazole-kindled mice. Phytomedicine 22(1):86–93

    Article  PubMed  Google Scholar 

  101. Ramani, R., et al., Antiepileptic activity of leaves of Leucas aspera. 2014, 2014. 6(3): p. 4.

  102. Sathwara JA, Bhandari AM (2016) Antiepileptic activity of Murraya koenigii leaf extracts. PharmaTutor 4:41–44

    CAS  Google Scholar 

  103. Karimzadeh F et al (2012) Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain. BMC Complement Altern Med 12(1):76

    Article  PubMed  PubMed Central  Google Scholar 

  104. Pushpa VH et al (2014) Evaluation of the anticonvulsant activity of ethanol extract of Psidium guajava (guava leaves) in albino mice. Int J Pharm Sci Res 5:4288–4292

    Google Scholar 

  105. Mandegary A et al (2012) Anticonvulsant activity and toxicity of essential oil and methanolic extract of Zhumeria majdae Rech, a unique Iranian plant in mice. Neurochem Res 37:2725–2730

    Article  CAS  PubMed  Google Scholar 

  106. Chen JW, Borgelt LM, Blackmer AB (2019) Cannabidiol: a new hope for patients with Dravet or Lennox-Gastaut syndromes. Ann Pharmacother 53(6):603–611

    Article  CAS  PubMed  Google Scholar 

  107. Asadi-Pooya AA (2018) Lennox-Gastaut syndrome: a comprehensive review. Neurol Sci 39(3):403–414

    Article  PubMed  Google Scholar 

  108. Wirrell, E.C., et al., Optimizing the diagnosis and management of Dravet syndrome: recommendations from a North American consensus panel. Pediatric Neurol, 2017. 68: p. 18–34. e3.

  109. Szaflarski JP et al (2018) Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results. Epilepsia 59(8):1540–1548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Devinsky O et al (2018) Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med 378(20):1888–1897

    Article  CAS  PubMed  Google Scholar 

  111. Thiele EA et al (2018) Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. The Lancet 391(10125):1085–1096

    Article  CAS  Google Scholar 

  112. Devinsky O et al (2019) Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial. Epilepsia 60(2):294–302

    Article  CAS  PubMed  Google Scholar 

  113. ClinicalTrials.gov, GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome.

  114. ClinicalTrials.gov, Antiepileptic Efficacy Study of GWP42003-P in Children and Young Adults With Dravet Syndrome (GWPCARE1).

  115. ClinicalTrials.gov, A Dose-ranging Pharmacokinetics and Safety Study of GWP42003-P in Children With Dravet Syndrome (GWPCARE1)

  116. Zeba Afrin, A.S., M.A Jafri, Divya Vohora, M Asif, Preliminary screening of a classical unani formulation majoon najah for anticonvulsant activity. Inter J Pharm Res, 2017. 9(3): p. 34–51.

  117. Schachter SC (2008) Complementary and alternative medical therapies. Curr Opin Neurol 21(2):184–189

    Article  PubMed  Google Scholar 

  118. Rosenberg EC et al (2017) Quality of life in childhood epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol. Epilepsia 58(8):e96–e100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Salehi, B., et al., Pharmacological Properties of Chalcones: A Review of Preclinical Including Molecular Mechanisms and Clinical Evidence. Frontiers in Pharmacology, 2021. 11(2068).

  120. Sharifi-Rad, J., et al., Cinnamomum Species: Bridging Phytochemistry Knowledge, Pharmacological Properties and Toxicological Safety for Health Benefits. Frontiers in Pharmacology, 2021. 12(882).

Download references

Acknowledgements

N.C-M. acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017). This work was supported by CONICYT PIA/APOYO CCTE AFB170007. This study was fully funded by the Fundamental Research Grant Scheme (FRGS/1/2018/SKK11/PERDANA/02/1) from the Ministry of Education, Malaysia.

Funding

This study was funded by the Fundamental Research Grant Scheme (FRGS/1/2018/SKK11/PERDANA/02/1) from the Ministry of Education, Malaysia. This study partially supported by Çanakkale Onsekiz Mart University (Scientific Research Projects, ID: FBA-2017-1268). This study partially supported by Çanakkale Onsekiz Mart University (Scientific Research Projects, ID: FBA-2017-1268).

Author information

Authors and Affiliations

  1. Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Javad Sharifi-Rad

  2. Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador

    Javad Sharifi-Rad

  3. Facultad de Ciencias de La Salud, Universidad Arturo Prat, Avda. Arturo Prat 2120, Iquique, Chile

    Cristina Quispe

  4. Departamento de Ciencias Básicas, Facultad de Ciencias, Universidad Santo Tomas, Santiago, Chile

    Jesús Herrera-Bravo

  5. Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, 4811230, Temuco, Chile

    Jesús Herrera-Bravo

  6. Department of Nutrition and Dietetics, Faculty of Pharmacy, University of Concepcion, 4070386, Concepcion, Chile

    Miquel Martorell

  7. Universidad de Concepción, Unidad de Desarrollo Tecnológico, UDT, 4070386, Concepcion, Chile

    Miquel Martorell

  8. Department of Pharmaceutical Technology, Avicenna Tajik State Medical University, Rudaki 139, Dushanbe, 734003, Tajikistan

    Farukh Sharopov

  9. Department of Molecular Biology and Genetics, Faculty of Arts and Science, Canakkale Onsekiz Mart University, Canakkale, 17020, Turkey

    Tugba Boyunegmez Tumer

  10. Graduate Program of Biomolecular Sciences, Institute of Natural and Applied Sciences, Canakkale Onsekiz Mart University, Canakkale, 17020, Turkey

    Begum Kurt

  11. School of Health and Biomedical Sciences, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia

    Chintha Lankatillake & Daniel A. Dias

  12. Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania

    Anca Oana Docea

  13. Pulmonology Department, Hospital Garcia de Orta, EPE Almada, 2801-951, Lisboa, Portugal

    Ana Catarina Moreira

  14. Department of Health Sciences, Faculty of Science, University of Mauritius, Réduit, 80837, Mauritius

    Mohamad Fawzi Mahomoodally & Devina Lobine

  15. Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal

    Natália Cruz-Martins

  16. Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135, Porto, Portugal

    Natália Cruz-Martins

  17. Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, 4200-135, Porto, Portugal

    Natália Cruz-Martins

  18. Chemical and Biochemical Processing Division, ICAR – Central Institute for Research on Cotton Echnology, Mumbai, 400019, India

    Manoj Kumar

  19. Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania

    Daniela Calina

Authors
  1. Javad Sharifi-Rad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristina Quispe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jesús Herrera-Bravo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Miquel Martorell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Farukh Sharopov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tugba Boyunegmez Tumer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Begum Kurt
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chintha Lankatillake
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Anca Oana Docea
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ana Catarina Moreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Daniel A. Dias
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Mohamad Fawzi Mahomoodally
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Devina Lobine
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Natália Cruz-Martins
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Manoj Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Daniela Calina
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

D.C., A.O.D. and J.S.-R. conceptualization, C.L., M.F.M., L.D., C.L., A.O.D., C.Q., and T.B.T. contributed to drafting and writing the manuscript. C.L., B.K., M.K., A.C.M., F.S. and M.M. were responsible for the collection of relevant literature. A.O.D., D.L., J.H.-B., D.A.D., C.Q., M.K., D.C. and J.S.-R. contributed to the conception of the figure, interpreted the results. J.S.-R., M.K., N.C.-M., and D.C. revised and supervised the whole process. All authors contributed equally, have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Javad Sharifi-Rad, Daniel A. Dias, Natália Cruz-Martins or Daniela Calina.

Ethics declarations

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sharifi-Rad, J., Quispe, C., Herrera-Bravo, J. et al. A Pharmacological Perspective on Plant-derived Bioactive Molecules for Epilepsy. Neurochem Res 46, 2205–2225 (2021). https://doi.org/10.1007/s11064-021-03376-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-021-03376-0

Keywords

Search

Navigation