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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.


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Type of Study: Research | Subject: Pharmacology

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