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Volume 12, Issue 3 (12-2022)                   cmja 2022, 12(3): 246-259 | Back to browse issues page


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Yaghooti H, Olapour S. Anticonvulsant and Anti-anxiety Effects of Royal Jelly in Adult Male Syrian Rats. cmja 2022; 12 (3) :246-259
URL: http://cmja.arakmu.ac.ir/article-1-896-en.html
1- Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University Tehran, Iran.
2- Department of Pharmacology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.; Department of Pharmacology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. , olapour.s@gmail.com
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Introduction
Seizure is a neurologic condition that occurs due to the excessive and abnormal discharge of cortical neurons [1]. The reason for seizure is unknown in most cases; in some patients, it occurs due to brain tumors, stroke, and hypoglycemia [23]. Individuals with seizures may experience temporary changes in behavior, sensations, and consciousness [4, 5]. Anxiety is a type of psychological health disorder that causes fear and several physical symptoms such as heart palpitations, and chest pain. Anxiety is associated with reduced quality of life [6, 7].
Although several medications are clinically used for managing patients with seizures or anxiety disorders, long-term treatment with two or more drugs may cause drug interactions, increasing the risk of toxic effects [1, 3]. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are mainly used for treating anxiety and social phobia. but these drugs have disadvantages, such as the slow onset of action, minimal efficacy in acute anxiety states, and relative risk of side effects [8, 9]. In this regard, complementary medicine combined with conventional medicine may offer more integrated therapeutic strategies with lower side effects [11]. Royal jelly is a honey bee secretion with anti-inflammatory, antioxidant, and neuroprotection properties. Royal jelly contains peptides, lipids, flavonoids, and other bioactive compounds [12, 13, 1415]. In this study, we aim to examine the possible protective effects of royal jelly against seizure and anxiety-like behaviors in Syrian rats.
Methods
Sixty adult male white Syrian rats weighing about 25-30 g were bought from the laboratory animal breeding center of Ahvaz Jundishapur University of Medical Sciences. They were kept under standard laboratory conditions and fed with proper food and water. Of 60 rats, 25 were randomly divided into five groups of 5. Animals were treated with intraperitoneal (i.p.) injections of normal saline, royal jelly (100, 200, and 400 mg/kg), and phenobarbital (40 mg/kg) 30 minutes prior to the induction of seizure with strychnine (3 mg/kg, i.p.). Then, the onset time of seizure, seizure duration, and mortality rate were recorded for each animal in 30 minutes. 
The anti-anxiety effect of royal jelly was evaluated using the elevated plus maze (EPM) test [20]. The remaining 35 rats were randomly divided into five groups of 7. Animals received normal saline, royal jelly (50, 100, and 200 mg/kg), or diazepam (2 mg/kg) intraperitoneally. After 30 minutes, rats were individually placed in the center of the EPM device and let them explore the platform for 5 minutes. The time spent in the open arms of the platform and frequency of entries into open arms were measured for each animal. One-way analysis of variance (ANOVA) was applied to examine the differences between the study groups, followed by Tukey’s post hoc test for multiple comparisons. P< 0.05 was statistically significant.
Results 
As shown in Table 1, the intraperitoneal injection of royal jelly at both doses of 200 and 400 mg/kg, 30 minutes before strychnine administration, significantly delayed the time of seizure onset to the control group (P<0.001).


Results also showed that royal jelly (200 and 400 mg/kg) significantly reduced convulsion duration (P<0.001) compared to the control group (Table 1). However, intraperitoneal injection of royal jelly at a 100 mg/kg dose had no significant effects on these parameters. The mortality rate was also reduced significantly after using three doses of royal jelly compared to the control group (P≤0.001). The standard anticonvulsant drug of phenobarbital (40 mg/kg, i.p.) blocked the seizures induced by strychnine. 
As shown in Table 2, in the EPM test, intraperitoneal injection of royal jelly at two doses of 50 and 100 mg/kg significantly increased the time spent in open arms and the number of open arm entries compared to the control group (P<0.05).


In contrast, intraperitoneal injection of royal jelly at 200 mg/kg dose had no significant effect on these parameters. Diazepam, the standard anxiolytic benzodiazepine, significantly increased the number of open arm entries and the time spent in open arms (P<0.001) (Figures 1 and 2).

Discussion
The findings revealed the anticonvulsant and anxiolytic-like properties of royal jelly in the experimental rats. Treatment with royal jelly dose-dependently increased the time for the onset of seizures. Furthermore, royal jelly administration reduced the seizure duration and the mortality rate, confirming its protective effect. In the EPM test, royal jelly injection increased the frequency of entries into open arms and the time spent in open arms. This suggests that royal jelly can modulate anxiety in rats. Our findings are consistent with the findings of Sefirin et al., who reported that royal jelly treatment of ovariectomized Wistar rats could reduce menopause-related anxiety and hot flushes using EPM and open-field tests [23]. Ito et al. demonstrated that administration of royal jelly or 10-hydroxy-trans-2-decenoic acid (the main lipid component of royal jelly) alleviated stress-induced symptoms of anxiety and depression in rats [24]. One of the royal jelly’s pharmacological properties is the capacity to scavenge free radicals, indicating that royal jelly is an effective natural antioxidant. A recent study using a rabbit model of Alzheimer’s disease reported that long-term administration of royal jelly reduced neuronal loss and enhanced anti-oxidative abilities in the rabbits’ cerebral cortex and hippocampus [25]. Overall, royal jelly has a prominent role in modulating seizure and anxiety-like behaviors in rats. Further clinical studies should be conducted to evaluate the effectiveness of royal jelly in preventing and treating patients with neuropsychiatric disorders. 

Ethical Considerations
Compliance with ethical guidelines

This study obtained its ethical approval from Ahvaz Jondishapur University of Medical Sciences (Code: IRAJUMS.REC.1395.413).

Funding
This study was funded by Ahvaz Jondishapur University of Medical Sciences.

Authors' contributions
The authors equally contributed to preparing this article

Conflicts of interest
The authors declare no conflict of interest.


References
  1. Pieróg M, Socała K, Wyska E, Poleszak E, Wlaź P. Effect of ellagic acid on seizure threshold in two acute seizure tests in mice. Molecules. 2021; 26(16):4841. [DOI:10.3390/molecules26164841] [PMID] [PMCID]
  2. Zaeri S, Emamghoreishi M. Acute and chronic effects of N-acetylcysteine on pentylenetetrazole-induced seizure and neuromuscular coordination in mice. Iranian Journal of Medical Sciences. 2015; 40(2):118-24. [PMID]
  3. Ghosh S, Sinha JK, Khan T, Devaraju KS, Singh P, Vaibhav K, et al. Pharmacological and therapeutic approaches in the treatment of epilepsy. Biomedicines. 2021; 9(5):470. [DOI:10.3390/biomedicines9050470] [PMID] [PMCID]
  4. Kwon OY, Park SP. Depression and anxiety in people with epilepsy. Journal of Clinical Neurology. 2014; 10(3):175-88. [DOI:10.3988/jcn.2014.10.3.175] [PMID] [PMCID]
  5. Seyedoshohadaee M, Salighedar G, Haghani H. [Evaluation of the relationship between life quality and circadian types and anxiety in Iranian Epilepsy association members with epilepsy in 2020 (Persian)]. Iran Journal of Nursing. 2021; 34(132):8-20. [DOI:10.52547/ijn.34.132.8]
  6. Olivier JD, Vinkers CH, Olivier B. The role of the serotonergic and GABA system in translational approaches in drug discovery for anxiety disorders. Frontiers in Pharmacology. 2013; 4:74. [DOI:10.3389/fphar.2013.00074] [PMID] [PMCID]
  7. Louvet S, Ischayek M, Danoff R, Faafp F. The current role of long-term benzodiazepines for the treatment of generalized anxiety. Osteopathic Family Physician. 2015; 7(1):19-25. [Link]
  8. Lewis G, Duffy L, Ades A, Amos R, Araya R, Brabyn S, et al. The clinical effectiveness of sertraline in primary care and the role of depression severity and duration (PANDA): A pragmatic, double-blind, placebo-controlled randomised trial. Lancet Psychiatry. 2019; 6(11):903-14. [DOI:10.1016/S2215-0366(19)30366-9] [PMID]
  9. Strawn JR, Geracioti L, Rajdev N, Clemenza K, Levine A. Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: An evidence-based treatment review. Expert Opinion on Pharmacotherapy. 2018; 19(10):1057-70. [DOI:10.1080/14656566.2018.1491966] [PMID] [PMCID]
  10. Kienitz R, Kay L, Beuchat I, Gelhard S, von Brauchitsch S, Mann C, et al. Benzodiazepines in the management of seizures and status epilepticus: A review of routes of delivery, pharmacokinetics, efficacy, and tolerability. CNS Drugs. 2022; 36(9):951-75. [PMID] [PMCID]
  11. Yuan H, Ma Q, Ye L, Piao G. The traditional medicine and modern medicine from natural products. Molecules. 2016; 21(5):559. [DOI:10.3390/molecules21050559] [PMID] [PMCID]
  12. Yoshida M, Hayashi K, Watadani R, Okano Y, Tanimura K, Kotoh J, et al. Royal jelly improves hyperglycemia in obese/diabetic KK-Ay mice. Journal of Veterinary Medical Science. 2017; 79(2):299-307. [DOI:10.1292/jvms.16-0458] [PMID] [PMCID]
  13. Arzi A, Olapour S, Yaghooti H, Sistani Karampour N. Effect of royal jelly on formalin induced-inflammation in rat hind paw. Jundishapur Journal of Natural Pharmaceutical Products. 2015; 10(1):e22466. [DOI:10.17795/jjnpp-22466] [PMID] [PMCID]
  14. Kunugi H, Mohammed Ali A. Royal jelly and its components promote healthy aging and longevity: From animal models to humans. International Journal of Molecular Sciences. 2019; 20(19):4662. [DOI:10.3390/ijms20194662] [PMID] [PMCID]
  15. Taavoni S, Barkhordari F, Goushegir A, Haghani H. Effect of Royal Jelly on premenstrual syndrome among Iranian medical sciences students: A randomized, triple-blind, placebo-controlled study. Complementary Therapies in Medicine. 2014; 22(4):601-6. [PMID]
  16. Hasanloei A, Salamat KM, Hosseini SA. Antioxidant effect of swimming training and royal jelly consumption in the hippocampus tissue of rats with alzheimer›s disease. Hormozgan Medical Journal. 2022; 26(1):62-7. [DOI:10.34172/hmj.2022.11]
  17. Azimpour M, Fathi M, Dezfoulian O. [The effect of royal jelly on depression and anxiety in an animal model of alzheimer›s disease (Persian)]. The Neuroscience Journal of Shefaye Khatam. 2021; 9(2):79-90. [DOI:10.52547/shefa.9.2.79]
  18. Weiser MJ, Grimshaw V, Wynalda KM, Mohajeri MH, Butt CM. Long-term administration of queen bee acid (QBA) to rodents reduces anxiety-like behavior, promotes neuronal health and improves body composition. Nutrients. 2017; 10(1):13. [DOI:10.3390/nu10010013] [PMID] [PMCID]
  19. Annafi OS, Umukoro S, Eduviere AT. Evaluation of the anticonvulsant and anxiolytic potentials of methyl jasmonate in mice. Scientia Pharmaceutica. 2014; 82(3):643-54. [DOI:10.3797/scipharm.1310-22] [PMID] [PMCID]
  20. Miladi-Gorji H, Vafaei AA, Rashidy-Pour A, Taherian AA, Jarrahi M, Emami-Abarghoie M, et al. Anxielytic effects of Portulaca oleracea aqueous extracts in mice. Journal of Medicinal Plants. 2006; 5(19):23-8. [Link]
  21. Zalkhani R. Several models of induction seizure and epilepsy in experimental animals. Journal of Research in Applied and Basic Medical Sciences. 2020; 6(4):252-61. [Link]
  22. Aduema W, Osim EE, Nwankwo AA. Using the elevated plus maze task in assessing anxiety and fear in Swiss white mice. Journal of Complementary Medicine and Alternative Healthcare. 2018; 6(1):001 -6. [Link]
  23. Sefirin D, Nange AC, Florette MT, Franklin ZG, Florence AC, Pierre K, et al. Royal jelly induced anxiolytic effects and prevent hot flushes in a menopausal model on wistar rat. Biomedical Journal of Scientific & Technical Research. 2019; 19:14557-66. [DOI:10.26717/BJSTR.2019.19.003356]
  24. Ito S, Nitta Y, Fukumitsu H, Soumiya H, Ikeno K, Nakamura T, et al. Antidepressant-like activity of 10-hydroxy-trans-2-decenoic acid, a unique unsaturated fatty acid of royal jelly, in stress-inducible depression-like mouse model. Evidence-Based Complementary and Alternative Medicine. 2012; 2012:139140. [PMID] [PMCID]
  25. Pan Y, Xu J, Jin P, Yang Q, Zhu K, You M, et al. Royal jelly ameliorates behavioral deficits, cholinergic system deficiency, and autonomic nervous dysfunction in ovariectomized cholesterol-fed rabbits. Molecules. 2019; 24(6):1149. [PMID] [PMCID]
  26. Hassan W, Silva CE, Mohammadzai IU, da Rocha JB, J LF. Association of oxidative stress to the genesis of anxiety: Implications for possible therapeutic interventions. Current Neuropharmacology. 2014; 12(2):120-39. [DOI:10.2174/1570159X11666131120232135] [PMID] [PMCID]
  27. Sudha K, Rao AV, Rao A. Oxidative stress and antioxidants in epilepsy. Clinica Chimica Acta. 2001; 303(1-2):19-24. [PMID]
  28. Martinello M, Mutinelli F. Antioxidant activity in bee products: A review. Antioxidants. 2021; 10(1):71. [PMID] [PMCID]
  1. Ali AM, Kunugi H. The effects of royal jelly acid, 10-hydroxy-trans-2-decenoic acid, on neuroinflammation and oxidative stress in astrocytes stimulated with lipopolysaccharide and hydrogen peroxide. Immunology. 2021; 1(3):212-22. [DOI:10.3390/immuno1030013]
  2. Kahnberg P, Lager E, Rosenberg C, Schougaard J, Camet L, Sterner O, et al. Refinement and evaluation of a pharmacophore model for flavone derivatives binding to the benzodiazepine site of the GABAA receptor. Journal of Medicinal Chemistry. 2002; 45(19):4188-201. [DOI:10.1021/jm020839k] [PMID]
  3. Ye Z, Kappelmann N, Moser S, Davey Smith G, Burgess S, Jones PB, et al. Role of inflammation in depression and anxiety: Tests for disorder specificity, linearity and potential causality of association in the UK Biobank. Eclinical Medicine. 2021; 38:100992. [DOI:10.1016/j.eclinm.2021.100992] [PMID] [PMCID]
Type of Study: Research | Subject: Pharmacology

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