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Effects of Hyssopus Officinalis Hydroalcoholic Extract on Pentylenetetrazol-Induced Convulsive Seizures in Rat

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Abstract

Hyssopus officinalis L. is one of the most important medicinal plants in traditional medicine used to treat seizures. In this study, we assessed the effects of H. officinalis hydroalcoholic extract against pentylenetetrazol (PTZ)-induced seizures in rat. The anti-seizure activity of the extract was assessed in three doses of 25, 50, and 100 mg/kg. Kindling was induced by intraperitoneal injection of PTZ (35 mg/kg) every 48 h, and H. officinalis extract was administered daily and behavioral tests performed. The possible involvement of GABA receptors in the extract activity was investigated using flumazenil. Tonic seizure threshold and mortality rate were measured following intraperitoneal injection of 60 mg/kg PTZ on the 14th day, following 14 days administration of H. officinalis hydroalcoholic extract. Blood and hippocampus samples were prepared to measure brain and serum antioxidant capacity, malondialdehyde (MDA), and nitric oxide (NO). Finally, the expression of GABA receptor gene in brain tissue was investigated. H. officinalis extract increased tonic seizure threshold and decreased mortality due to PTZ. Flumazenil, as a GABA receptor antagonist, reduced the tonic seizure threshold. Extract treatment significantly improved memory and learning, increased brain antioxidant capacity, decreased brain MDA and NO in kindled rats. It also increased GABA receptor gene expression in pre-treated groups compared to the negative control group. H. officinalis extract probably exerts potential antiepileptic effects through the GABAergic system. Also, H. officinalis extract has a supportive effect against hippocampal neuronal damage and improves memory and learning in kindled rats.

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Data Availability

Data regarding the present study are available at Medical Plants Research Center, Shahrekord University of Medical Science.

Abbreviations

PTZ:

Pentylenetetrazol.

MDA:

Malondialdehyde.

NO:

Nitric oxide.

TPTZ:

tripiridyltriazine.

NEDD:

N-1-naphthylnethylenediamine .

References

  1. Tastemur Y, Gumus E, Ergul M, Ulu M, Akkaya R, Ozturk A, Taskiran AS (2020) Positive effects of angiotensin-converting enzyme (ACE) inhibitor, captopril, on pentylenetetrazole-induced epileptic seizures in mice. Trop J Pharm Res 19:637–643

    Article  CAS  Google Scholar 

  2. Devi PU, Manocha A, Vohora D (2008) Seizures, antiepileptics, antioxidants and oxidative stress: an insight for researchers. Expert Opin Pharmaco 9(18):3169–3177

    Article  CAS  Google Scholar 

  3. Metcalf CS, Huntsman M, Garcia G, Kochanski AK, Chikinda M, Watanabe E, Underwood T, Vanegas F, Smith MD, Steve White H, Bulaj G (2019) Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs. Front Neurol 10:277

    Article  PubMed  PubMed Central  Google Scholar 

  4. Shin EJ, Jeong JH, Chung YH, Kim WK, Ko KH, Bach JH, Hong JSh, Yoneda Y, Kim HCh (2011) Role of oxidative stress in epileptic seizures. Neurochem Int 59(2):122–137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Meldrum BS (1994) The role of glutamate in epilepsy and other CNS disorders. Neurology 44(11):S14–S23

    CAS  PubMed  Google Scholar 

  6. Miyazaki H, Matsuura H, Yanagiya C, Mizutani J, Tsuji M, Ishihara C (2003) Inhibitory Effects of Hyssop (Hyssopus officinalis) Extracts on Intestinal ALPHA.-Glucosidase Activity and Postprandial Hyperglycemia. J Nutri Sci Vitaminol 49(5):346–349

    Article  CAS  Google Scholar 

  7. Rudolph U, Möhler H (2014) GABAA receptor subtypes: Therapeutic potential in Down syndrome, affective disorders, schizophrenia, and autism. Annu Rev Pharmacol Toxicol 54:483–507

    Article  CAS  PubMed  Google Scholar 

  8. Singh T, Mishra A, Goel RK (2021) PTZ kindling model for epileptogenesis, refractory epilepsy, and associated comorbidities: relevance and reliability. Metab Brain Dis 1573–1590

  9. Bazan NG, Tu B, Rodriguez de Turco EB (2002) What synaptic lipid signaling tells us about seizure-induced damage and epileptogenesis. Prog Brain Res 135:175–185

    Article  CAS  PubMed  Google Scholar 

  10. Jesberger JA, Richardson JS (1991) Oxygen free radicals and brain dysfunction. Int J Neurosci 57(1–2):1–17

    Article  CAS  PubMed  Google Scholar 

  11. Angelatou F, Pagonopoulou O, Kostopoulos G (1990) Alterations of A1 adenosine receptors in different mouse brain areas after pentylentetrazol-induced seizures, but not in the epileptic mutant mouse ‘tottering’. Brain Res 534(1):251–256

    Article  CAS  PubMed  Google Scholar 

  12. Tahir M, Khushtar M, Fahad M, Rahman A (2018) Phytochemistry and pharmacological profile of traditionally used medicinal plant Hyssop (Hyssopus officinalis L.). J Appl Pharm Sci 8(07):132–140

    Article  CAS  Google Scholar 

  13. Fathiazad F, Hamedeyazdan S (2011) A review on Hyssopus officinalis L.: Composition and biological activities. Acad Journals 5(17):1959–1966

    Google Scholar 

  14. Javadi B, Sahebkar A, Emami S (2017) Medicinal plants for the treatment of asthma: A traditional Persian medicine perspective. Curr Pharm Des 23:1623–1632

    Article  CAS  PubMed  Google Scholar 

  15. Özer H, Şahin F, Kılıç H, Güllüce M (2005) Essential oil composition of Hyssopus officinalis L. subsp. angustifolius (Bieb.) Arcangeli from Turkey. Flavour Fragr J 20:42–44

    Article  Google Scholar 

  16. Gholami M, Jafari F, Baradaran Z, Amri J, Azhdari-Zarmehri H, Sadegh M (2020) Effects of aqueous extract of Hyssopus officinalis on seizures induced by pentylenetetrazole and hippocampus mRNA level of iNOS in rats. Avicenna J Phytomedicine 10(3):213–221

    CAS  Google Scholar 

  17. Ullah HA, Zaman S, Juhara F, Akter L, Tareq SM, Masum EH, Bhattacharjee R (2014) Evaluation of antinociceptive, in-vivo & in-vitro anti-inflammatory activity of ethanolic extract of Curcuma zedoaria rhizome. BMC Complem Altern M 14(1):346

    Article  Google Scholar 

  18. Pohle W, Becker A, Grecksch G, Juhre A, Willenberg A (1997) Piracetam prevents pentylenetetrazol kindling-induced neuronal loss and learning deficits. Seizure 6(6):467–474

    Article  CAS  PubMed  Google Scholar 

  19. Sridhar K, Charles AL (2019) In vitro antioxidant activity of Kyoho grape extracts in DPPH and ABTS assays: estimation methods for EC50 using advanced statistical programs. Food Chem 275:41–49

    Article  CAS  PubMed  Google Scholar 

  20. Derakhshan Z, Ferrante M, Tadi M, Ansari F, Heydari A, Hosseini MS, Conti GO, Sadrabad EKh (2018) Antioxidant activity and total phenolic content of ethanolic extract of pomegranate peels, juice and seeds. Food Chem Toxicol 114:108–111

    Article  CAS  PubMed  Google Scholar 

  21. Dhir A (2012) Pentylenetetrazol (PTZ) kindling model of epilepsy. Curr Protoc Neurosci 58(1):1–937

    Google Scholar 

  22. Ghazvini H et al (2016) Estrogen and progesterone replacement therapy prevent methamphetamine-induced synaptic plasticity impairment in ovariectomized rats. Addict health 8(3):145

    PubMed  PubMed Central  Google Scholar 

  23. Amiri S et al (2016) NMDA receptors are involved in the antidepressant-like effects of capsaicin following amphetamine withdrawal in male mice. Neuroscience 329:122–133

    Article  CAS  PubMed  Google Scholar 

  24. Tripathi Y, Saini N (2019) Total phenolic, total flavonoid content and antioxidant efficacy of leaves of Eupatorium adenophorum. Int J Pharma Bio Sci 10(2):157–166

    CAS  Google Scholar 

  25. Peay DN, Saribekyan HM, Parada PA, Hanson EM, Badaruddin BS, Judd JM, Donna ME, Padilla-Garcia D, Conrad CD (2020) Chronic unpredictable intermittent restraint stress disrupts spatial memory in male, but not female rats. Behav Brain Res 383:112519

    Article  PubMed  PubMed Central  Google Scholar 

  26. Khalili M, Roghani M, Ekhlasi M (2010) The effect of aqueous crocus sativus L. extract on intracerebroventricular streptozotocin-induced cognitive deficits in rat: a behavioral analysis. Iran J Pharm Res 185–191

  27. Johnston GA (2005) GABAA receptor channel pharmacology. Curr Pharm Design 11(15):1867–1885

    Article  CAS  Google Scholar 

  28. Poucet B (1993) Spatial cognitive maps in animals: new hypotheses on their structure and neural mechanisms. Psychol Rev 100(2):163–182

    Article  CAS  PubMed  Google Scholar 

  29. Duarte FS, Marder M, Hoeller AA, Duzzioni M, Mendes BG, Pizzolatti MG, De Lima TCM (2008) Anticonvulsant and anxiolytic-like effects of compounds isolated from Polygala sabulosa (Polygalaceae) in rodents: in vitro and in vivo interactions with benzodiazepine binding sites. Psychopharmacology 197(3):351–360

    Article  CAS  PubMed  Google Scholar 

  30. Avallone R, Zanoli P, Puia G, Kleinschnitz M, Schreier P, Baraldi M (2000) Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla. Biochem Pharmacol 59(11):1387–1394

    Article  CAS  PubMed  Google Scholar 

  31. Viola H, Wolfman C, Marder M, Goutman J, Bianchin M, Wasowski C, Calvo DJ, Izquierdo I, Paladini AC, Medina JH (2000) 6-Chloro-3′-nitroflavone is a potent ligand for the benzodiazepine binding site of the GABA A receptor devoid of intrinsic activity. Pharmacol Biochem Behav 65(2):313–320

    Article  CAS  PubMed  Google Scholar 

  32. Hashemi P, Babaei JF, Vazifekhah S, Nikbakht F (2019) Evaluation of the neuroprotective, anticonvulsant, and cognition-improvement effects of apigenin in temporal lobe epilepsy: Involvement of the mitochondrial apoptotic pathway. Iran J Basic Med Sci 22(7):752–758

    PubMed  PubMed Central  Google Scholar 

  33. Chang CY, Lin TY, Lu CW, Wang CC, Wang YC, Chou SSP, Wang SJ (2015) Apigenin, a natural flavonoid, inhibits glutamate release in the rat hippocampus. Eur J Pharmacol 762:72–81

    Article  CAS  PubMed  Google Scholar 

  34. Nassiri-Asl M, Mortazavi SR, Samiee-Rad F, Zangivand AA, Safdari F, Saroukhani S, Abbasia E (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 

  35. Spencer JP (2009) Flavonoids and brain health: multiple effects underpinned by common mechanisms. Genes Nutr 4(4):243–250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Uzüm G, Akgün-Dar K, Aksu U (2010 Nov) The effects of atorvastatin on memory deficit and seizure susceptibility in pentylentetrazole-kindled rats. Epilepsy Behav 19(3):284

  37. Júnior JS, de Almeida AA, Tomé Ada R, Citó AM, Saffi J, de Freitas RM (2011) Evaluation of possible antioxidant and anticonvulsant effects of the ethyl acetate fraction from Platoniainsignis Mart. (Bacuri) on epilepsy models. Epilepsy Behav 22(4):678–684

    Article  PubMed  Google Scholar 

  38. Costello DJ, Delanty N (2004) Oxidative injury in epilepsy: potential for antioxidant therapy. Expert Rev Neurother 4(3):541–537

    Article  CAS  PubMed  Google Scholar 

  39. Wang J, Zhang YJ, Du S (2012) The protective effect of curcumin on Aβ□ induced aberrant cell cycle reentry on primary cultured rat cortical neurons. Eur Rev Med Pharmacol Sci 16(4):445–454

    CAS  PubMed  Google Scholar 

  40. Yaribeygi H, Panahi Y, Javadi B, Sahebkar A (2018) The Underlying Role of Oxidative Stress in Neurodegeneration: A Mechanistic Review. CNS Neurol Disord Drug Targets 17:207–215

    Article  CAS  PubMed  Google Scholar 

  41. Shekh-Ahmad T, Kovac S, Abramov AY, Walker MC (2019) Reactive oxygen species in status epilepticus. Epilepsy Behav 101:106410

    Article  CAS  PubMed  Google Scholar 

  42. Wolff SP, Dean R (1987) Glucose autoxidation and protein modification. The potential role of ‘autoxidative glycosylation’in diabetes. Biochem J 245(1):243–250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Rafieian-Kopaei M, Baradaran A, Rafieian M (2013) Oxidative stress and the paradoxical effects of antioxidants. J Res Med Sci 18(7):628

    Google Scholar 

  44. Arhan E, Serdaroghu A, Ozturk B, Ozturk HS, Ozcelik A, Kurt N, Kutsal E, Sevinc N (2011) Effects of epilepsy and antiepileptic drugs on nitric oxide, lipid peroxidant and xanthine oxidase system in children whith idiopathic epilepsy. Seizure 20(2):138–142

    Article  PubMed  Google Scholar 

  45. Jutila L, Immonen A, Partanen K, Partanen J, Mervaala E, Ylinen A, Alafuzoff I, Paljärvi L, Karkola K, Vapalahti M, Pitkänen A (2002) Neurobiology of epileptogenesis in the temporal lobe.Adv Tech Stand Neurosurg 3–22

  46. Pavlova T, Yakovlev A, Stepanichev MY, Mendzheritskii A, Gulyaeva N (2004) Pentylenetetrazole kindling induces activation of caspase-3 in the rat brain. Neurosci Behav Physiol 34(1):45–47

    Article  CAS  PubMed  Google Scholar 

  47. Huang X, Liu T, Gu J, Luo X, Ji R, Cao Y, Xue H, Wong JTF, Wong BL, Pei G, Jiang H, Chenet K (2001) 3D-QSAR Model of flavonoids binding of benzodiazepine site in GABAA receptors. J Med Chem 4(12):1883–1891

    Article  Google Scholar 

  48. Hanrahan JR, Chebib M, Davucheron NLM, Hall BJ, Johnston GAR (2003) Semisynthetic preparation of amentoflavone: a negative modulator at GABAA receptors. J Bioor Med Chem Lett 13:2281–2284

    Article  CAS  Google Scholar 

  49. Wolfson P, Hoffmann DL (2003) An investigation into the efficacy of scutellaria lateriflora in healthy volunteers. J Altern Th 9(2):74–78

    CAS  Google Scholar 

  50. Vauzour D, Vafeiadou K, Rodriguez-Mateos A, Rendeiro C, Spencer J (2008) The neuroprotective potential of flavonoids: a multiplicity of effects. Genes Nutr 3(3–4):115–126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors gratefully thank the Research and Technology Deputy of Shahrekord University of Medical Sciences for all supports provided.

Funding

This work was supported by Shahrekord University of Medical Sciences (Grant number 1148).

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Authors and Affiliations

  1. Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

    Neda Fatahinezhad, Zahra Lorigooini, Zahra Rabiei & Mahmoud Rafieian-Kopaei

  2. Department of Biology, Shahrekord University, Shahrekord, Iran

    Mehran Arabi

  3. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

    Sedighe Kazemi sheykhshabani

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  1. Neda Fatahinezhad
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Contributions

NF, ZL, MA, ZR, SK, MRK carried out the experiments, participated in the design of the study, performed the statistical analysis and drafted the manuscript. NF and ZR provided expertise in the behaviors analysis. ZR and ZL participated in the design and coordination of the study. ZR and MRK edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Mahmoud Rafieian-Kopaei.

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All stages of experimentation were carried out in accordance with the regulations of the University and the Guide for the Care and Use of Laboratory Animals of National Institutes of Health and Guide for the Care and Use of Laboratory Animals. Full efforts were made to diminish the use of animals and to improve their wellbeing.

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Fatahinezhad, N., Lorigooini, Z., Arabi, M. et al. Effects of Hyssopus Officinalis Hydroalcoholic Extract on Pentylenetetrazol-Induced Convulsive Seizures in Rat. Neurochem Res 47, 3792–3804 (2022). https://doi.org/10.1007/s11064-022-03759-x

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