Investigation of dose related effects of propolis on anxiety and some biochemical parameters with sympathetic skin response and increased T-maze

Abstract

Aim: Propolis has been shown to have anti-microbial, antioxidant, anti-tumor, anxiolytic and anti-inflammatory effects. However, to the best of our knowledge, there are no studies on its anxiogenic effects. In this study, we aimed to investigate the effects of different doses of propolis on anxiety in rats with cold stress via sympathetic skin response (electrodermal activity) and elevated T maze.
Methods: Forty Wistar albino male rats were used in the study, divided into four groups: The control group, low dose (10 mg/kg PRO), medium dose (30 mg/kg PRO) and high dose propolis groups (50 mg/kg PRO). Propolis was administered via gavage to all rats except the control group. Twenty minutes after injection, the anxiety scores of the rats were evaluated with an elevated T-maze, and their electrodermal activities (EDA) were measured. At the end of the experiment, some enzymatic and lipid values were measured with malondialdehyde (MDA) in blood samples.
Results: The percentage of time spent on open arms and the number of open arm entries were lower in the 10mg/kg PRO group, while an increase was observed in the 30 mg/kg PRO group. EDA values were lower in the 30 mg / kg PRO (P=0.012; P=0.02, respectively) and 50 mg / kg PRO (P=0.013, P=0.02, respectively) groups as compared to the control group. MDA was significantly lower in the 30 mg/kg PRO and 50 mg/kg PRO groups. While AST value increased in the 30 mg / kg PRO group, ALT value decreased. Total cholesterol and triglyceride values were significantly lower in the 50 mg / kg PRO group. HDL value increased significantly after administration of propolis and LDL value decreased significantly only in the 10 mg/kg PRO group.
Conclusions: According to the results obtained by EDA and T labyrinth methods, while low and high dose propolis, which was administered to rats after cold stress, showed an anxiogenic effect, medium dose propolis exerted an anxiolytic effect. It also decreased MDA values in the medium and high dose groups and influenced enzymatic and lipid values in favor of the rat. It was concluded that the anxiety-related effects of propolis were dose-dependent.

Keywords

• Propolis,EDA,Anxiety,T maze

Propolisin anksiyeteye ve bazı biyokimyasal parametrelere etkilerinin sempatik deri cevabı ve yükseltilmiş T labirent ile araştırılması

Öz

Amaç: Propolisin anti-mikrobiyal, antioksidan, anti-tümör, anksiyolitik ve anti-inflamatuar etkilere sahip olduğu gösterilmiştir. Ancak literatürde propolisin anksiyojenik etkisi konusundaki çalışmalara rastlanılmamıştır. Bu çalışmamızda, soğuk stresi oluşturulmuş sıçanlarda propolisin farklı dozlarının anksiyeteye etkilerinin sempatik deri cevabı (elektrodermal aktivite) ve yükseltilmiş T labirent ile araştırılması amaçlandı.
Yöntemler: Çalışmada 40 adet Wistar albino erkek sıçan kullanıldı. Kontrol grubu, düşük doz (10 mg/kg PRO), orta doz (30 mg/kg PRO) ve yüksek doz propolis (50 mg/kg PRO) grupları oluşturularak, kontrol grubu hariç diğer gruplara propolis gavaj yoluyla uygulandı. Enjeksiyondan 20 dakika sonra, sıçanların anksiyete skorları yükseltilmiş T-labirent ile değerlendirildi ve daha sonra da elektrodermal aktiviteleri (EDA) ölçüldü. Deney sonunda kan örneklerinde, spektrofotometrik olarak malondialdehit (MDA) ile bazı enzimatik ve lipid değerleri ölçüldü.
Bulgular: 10 mg/kg PRO grubunda açık kolda harcanan zamanın yüzdesi ve açık kola giriş sayısı, diğer gruplara göre daha düşük bulunurken 30 mg/kg PRO grubunda artış gözlendi. EDA, 30 mg/kg PRO (sırasıyla, P=0,012, P=0,02) ve 50 mg/kg PRO (sırasıyla, P=0,013, P=0,02 gruplarında kontrole kıyasla daha düşüktü. MDA’nın 30 mg/kg PRO ve 50 mg/kg PRO gruplarında önemli oranda düşük olduğu görüldü. 30 mg/kg PRO grubunda AST değeri artış gösterirken ALT değerinde azalmanın olduğu görüldü. Toplam kolesterol ve trigliserit değerleri 50 mg/kg PRO grubunda anlamlı olarak düşüktü. HDL değerinin düşük doz propolisten uygulamasından itibaren anlamlı yükseldiği, LDL değerinin ise sadece 10 mg/kg PRO grubunda anlamlı azaldığı olduğu görüldü.
Sonuçlar: EDA ve T-labirent yöntemleriyle elde edilen sonuçlara göre düşük ve orta doz propolis anksiyetik etki yaparken, yüksek doz propolis anksiyolitik etki göstermiştir. Ayrıca sıçanlara soğuk stres sonucunda uygulanan propolisin MDA değerlerini orta ve yüksek doz gruplarında düşürdüğü, enzimatik ve lipid değerlerinde ise organizma lehine olumlu değişimlere sebep olduğu görüldü. Dolayısıyla propolisin anksiyeteye ilişkin yanıtlarının, doza bağlı etkilerine göre değiştiği sonucuna varılmıştır.

Anahtar Kelimeler

• Propolis,EDA,Anksiyete,T-labirent

References

1. 1. Gupta D, Radhakrishnan M, Kurhe. Anxiolytic-like effects of alverine citrate in experimental Mouse models of anxiety. European Journal of Pharmacology. 2014;742:94–101.
2. 2. Kalueff AV, Wheaton M, Murphy DL. What's wrong with my mouse model: advances and strategies in animal modeling of anxiety and depression. Behav Brain Res. 2007;179:1–18.
3. 3. Griebel G, Holmes A. 50 years of hurdles and hope in anxiolytic drug discovery. Nat. Rev Drug Discov. 2013;12:667–87.
4. 4. Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol. 2003;463:3–33.
5. 5. Dolu N, Keloglan S, Bitiktas S, Cug S. The effects of the enriched environment on sympathetic skin response in pentylenetetrazol-kindled rats. Biomed Environ Sci. 2013;26(5):394–7.
6. 6. Andor T, Gerlach AL, Rist F. Superior perception of phasic physiological arousal and the detrimental consequences of the conviction to be aroused on worrying and metacognitions in GAD. J Abnorm Psychol. 2008;117:193–205.
7. 7. Bradley MM, Codispoti M, Cuthbert BN, Lang PJ. Emotion and motivation I: defensive and appetitive reactions in picture processing. Emotion. 2001;1:276–98.
8. 8. Naccache L, Dehaene S, Cohen L, Habert MO, Guichart Gomez E, Galanaud D. Effortless control: executive attention and conscious feeling of mental effort are dissociable. Neuropsychologia. 2005;43:1318–28.

9. 9. Dolu N, Acer H, Kara AY. Investigation of dose-related effects of carnosine On anxiety with sympathetic skin response and T-maze. Acta Medica. 2014;57(3):112–8.
10. 10. Dolu N, Yüksek A, Sizer A, Alay M. Arousal and continuous attention during Ramadan intermittent fasting. J Basic Clin Physiol Pharmacol. 2007;18:315–22.
11. 11. Quermonne MA, Nammathao B, Louchahi-Raoul J, Marcy R. Skin conductance reaction–habituation test, an elementary model of anxiety as a tool to assess anxiogenic activities of some drugs. Prog. Neuropsychopharmacol. Biol Psychiatry. 1993;17:311–8.
12. 12. Dolu N. Dose-related anxiogenic effect of glycine in the elevated plus maze and in electrodermal activity. J Basic Clin Physiol Pharmaco. 2007;18:141–7.
13. 13. Castaldo S, Capasso F. Propolis, an old remedy used in modern medicine. Fitoterapia. 2002;73:1-6.
14. 14. Drago L, Mombelli B, De Vecchi E, Fassina MC, Tocalli L, Gismondo MR. In vitro antimicrobial activity of propolis dry extract. J Chemother. 2000;12(5):390-5.
15. 15. Koc AN, Silici S, Ayangil D, Ferahbas A, Cankaya S. Comparison of in vitro activities of antifungal drugs and ethanolic extract of propolis against Trichophyton rubrum and T. mentagrophytes by using a microdilution assay. Mycoses. 2005;48(3):205-10.
16. 16. Nakajima Y, Shimazawa M, Mishima S, Hara H. Water extract of propolis and its main constituents, caffeoylquinic acid derivatives, exert neuroprotective effects via antioxidant actions. Life Sci. 2007;80(4):370-7.
17. 17. Preshaw PM, Taylor JJ. How has research into cytokine interactions and their role in driving immune responses impacted our understanding of periodontitis? J Clin Periodontol. 2011;38:60-84.
18. 18. Li YJ, Xuan HZ, Shou QY, Zhan ZG, Lu X, Hu FL. Therapeutic effects of propolis essential oil on anxiety of restraint-stressed mice. Hum Exp Toxicol. 2012;31(2):157-65.
19. 19. Reis JS, Oliveira GB, Monteiro MC, Machado CS, Torres YR, Prediger RD, Maia CS. Antidepressant and anxiolytic-like activities of an oil extract of propolis in rats. Phytomedicine. 2014;25;21(11):1466-72.
20. 20. Baldwin DS, Anderson IM, Nutt DJ, Allgulander C, Bandelow B, den Boer JA, et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British association for psychopharmacology. J Psychopharmacol. 2014;28:403–39.
21. 21. Edelberg R, Wright DJ. Two galvanic skin response effector organs and their stimulus specificity. Psychophysiology. 1964;1:39-47.
22. 22. Uncini A, Pullman SL, Lovelace RE, Gambi D. The sympathetic skin response: normal values, elucidation of afferent components and application limits. J Neurol Sci. 1988;87:299-4.
23. 23. Dolu N, Ozesmi Ç. Assessment of the dose-dependent effect of tryptophan on anxiety with electrodermal activity and elevated plus maze test in mice. Bulletin of Clinical Psychopharmacology. 2007;17:74-9.
24. 24. Mohammadzadeh S, Sharriatpanahi M, Hamedi M, Amanzadeh Y, Ebrahimi SES, Ostad SN. Antioxidant power of Iranian propolis extract. Food Chem. 2007;103:729-33.
25. 25. Hosnuter M, Gürel A, Babucçu O, Armutcu F, Kargi E, Isıkdemir A.The effect of capeon lipid peroxidation and nitric oxide levels in the plasma of rats following thermal injury. Burns. 2004;30:121-5.
26. 26. Eraslan G, Kanbur M, Silici S. Evaluation of propolis effects on some biochemical parameters in rats treated with sodium fluoride. Pesticide Biochem and Physiol. 2007;88:273-83.
27. 27. Kolankaya D, Selmanoglu G, Sorkun K, Salih B. Protective effects of Turkish propolis on alcohol-ınduced serum lipid changes and liver ınjury ın male rats. Food Chem. 2002;78:213-17.
28. 28. Mani F, Damasceno HCR, Novelli ELB, Martins EAM, Sforcin JM. Propolis: Effect of different concentrations extracts and intake period on seric biochemical variables. J of Ethnopharm. 2006;105:95-8.
29. 29. Newairy ASA, Salama AF, Hussien HM, Yousef MI. Propolis alleviates aluminium induced lipid peroxidation and biochemical parameters in male rats. Food and Chem Toxicol. 2009;47:1093-8.
30. 30. Alves MJQF, Mesquita FF, Sakaguti M, Tardivo AC. Hypocholesterolemic effect of propolis caffeic acids. Revist Brasil de Plant Med. 2008;10:100-5.