Repeated systemic administration of the cinnamon essential oil possesses anti-anxiety and anti-depressant activities in mice

Document Type : Original Article

Authors

1 Research Committee, Sabzevar University of Medical Sciences, Sabzevar, Iran

2 Traditional and Complementary Medicine Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran

3 Cellular and Molecular Research Center, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran

Abstract

Objective(s): The present study aimed to evaluate the putative antidepressant and anti-anxiety effects of the cinnamon essential oil when administered acute (for 3 doses) and sub-acute (for 14 days) to mice.
Materials and Methods: In an acute experimental study, forced swim test (FST) was conducted to evaluate the antidepressant-like behavior of animals treated with the intraperitoneal (IP) essential oil of cinnamon in triple doses (0.5, 1, and 2 mg/kg). In a sub-acute study (14 days in 24-hr intervals) antidepressant-like effects of essential oil (0.5, 1, and 2 mg/kg) with the same route were assessed in FST and tail suspension test (TST). Anti-anxiety and motor activities were evaluated using elevated plus-maze (EPM) and open field tests, respectively. Determination of different constituents within the sample oil was via gas chromatography–mass spectrometry (GC–MS) analysis.
Results: Repetitive administration of cinnamon essential oil (0.5, 1, 2 mg/kg) during 14 days significantly decreased the time of immobility in both FST and TST as compared to the control group. Mice treated with oil at the dose of 2 mg/kg spent a longer time and had more entries into the open arms of EPM as compared with the vehicle-treated ones. According to GC-MS analysis, 46 chemical compounds were identified in the studied cinnamon essential oil with the main constituent being trans-cinnamaldehyde (87.32%).
Conclusion: Cinnamon essential oil might be used as an adjunctive therapy in improving symptoms of depressive and anxiety disorders. However, dose-response effects need further evaluation. Trans-cinnamaldehyde might be responsible for the beneficial effect observed.

Keywords

References

1. Maletic V, Robinson M, Oakes T, Iyengar S, Ball SG, Russell J. Neurobiology of depression: an integrated view of key findings. Int J Clin Pract 2007; 61:2030-2040.
2. Young JJ, Silber T, Bruno D, Galatzer-Levy IR, Pomara N, Marmar CR. Is there progress? An overview of selecting biomarker candidates for major depressive disorder. Front Psychiatr 2016; 7:72.
3. Bschor T, Kilarski LL. Are antidepressants effective? A debate on their efficacy for the treatment of major depression in adults. Expert Rev Neurother 2016; 16:367-374.
4. Gartlehner G, Gaynes BN, Amick HR, Asher G, Morgan LC, Coker-Schwimmer E, et al. Nonpharmaco-logical versus pharmacological treatments for adult patients with major depressive disorder: Rockville (MD): Agency for Healthcare Research and Quality (US); 2015.
5. Fajemiroye JO, da Silva DM, de Oliveira DR, Costa EA. Treatment of anxiety and depression: medicinal plants in retrospect. Fundam Clin Pharmacol 2016; 30:198-215.
6. Ardebili Dorri S, Hosseinzadeh H, Abnous K, Vahdati Hasani F, Yazdian Robati R, Razavi BM. Involvement of brain-derived neurotrophic factor (BDNF) on malathion induced depressive-like behavior in subacute exposure and protective effects of crocin. Iran J Basic Med Sci 2015; 18:958-966.
7. Bharat B Aggarwal, Kunnumakkara AB. Molecular targets and therapeutic uses of spices. Modern uses for ancient medicine. Mol Nutr Food Res 2013; 57:1510-1528.
8. Lee SH, Lee SY, Son DJ, Lee H, Yoo HS, Song S, et al. Inhibitory effect of 2′-hydroxycinnamaldehyde on nitric oxide production through inhibition of NF-κB activation in RAW 264.7 cells. Biochem Pharmacol 2005; 69:791-799.
9. White A, Nunes C, Escudier M, Lomer MC, Barnard K, Shirlaw P, et al. Improvement in orofacial granulomato-sis on a cinnamon‐and benzoate‐free diet. Inflamm Bowel Dis 2006; 12:508-514.
10. Molania T, Moghadamnia AA, Pouramir M, Aghel S, Moslemi D, Ghassemi L, et al. The effect of cinnamaldehyde on mucositis and salivary antioxidant capacity in gamma-irradiated rats (a preliminary study). Daru  2012; 20:89.
11. Sahib AS. Anti-diabetic and antioxidant effect of cinnamon in poorly controlled type-2 diabetic Iraqi patients: A randomized, placebo-controlled clinical trial. J Intercult Ethnopharmacol 2016; 5:108-113.
12. Blevins SM, Leyva MJ, Brown J, Wright J, Scofield RH, Aston CE. Effect of cinnamon on glucose and lipid levels in non insulin-dependent type 2 diabetes. Diabetes Care 2007; 30:2236-2237.
13. Nabavi SF, Di Lorenzo A, Izadi M, Sobarzo-Sanchez E, Daglia M, Nabavi SM. Antibacterial effects of cinnamon: From farm to food, cosmetic and pharmaceutical industries. Nutrients 2015; 7:7729-7748.
14. Zhu ZP, Zhang MF, Shen YQ, Chen GJ. Pharmacological study on spleen-stomach warming and analgesic action of Cinnamomum cassia Presl. Zhongguo Zhong Yao Za Zhi 1993; 18:553-7, 14-15.
15. Kamath JV, Rana AC, Chowdhury AR. Pro-healing effect of Cinnamomum zeylanicum bark. Phytother Res 2003; 17:970-972.
16. Chen TW, Tsai KD, Yang SM, Wong HY, Liu YH, Cherng J, et al. Discovery of a novel anti-cancer agent targeting both topoisomerase I & II as well as telomerase activities in human lung adenocarcinoma A549 cells in vitro and in vivo: Cinnamomum verum component cuminaldehyde. Curr Cancer Drug Targets 2016; 16:796-806.
17. Kim SH, Hyun SH, Choung SY. Anti-diabetic effect of cinnamon extract on blood glucose in db/db mice. J Ethnopharmacol 2006; 104:119-123.
18. Nyadjeu P, Nguelefack-Mbuyo EP, Atsamo AD, Nguelefack TB, Dongmo AB, Kamanyi A. Acute and chronic antihypertensive effects of Cinnamomum zeylanicum stem bark methanol extract in L-NAME-induced hypertensive rats. BMC Complement Altern Med 2013; 13:27.
19. Frydman-Marom A, Levin A, Farfara D, Benromano T, Scherzer-Attali R, Peled S, et al. Orally administrated cinnamon extract reduces beta-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models. PloS One 2011; 6:e16564.
20. Khasnavis S, Pahan K. Cinnamon treatment upregulates neuroprotective proteins Parkin and DJ-1 and protects dopaminergic neurons in a mouse model of Parkinson's disease. J Neuroimmune Pharmacol 2014; 9:569-581.
21. National Research, Council. Guide for the care and use of laboratory animals. National Academy Press. Washington, D. C. 1996.
22. Dashti-R MH, Qane MD, Shefaie F, Nazemian Yazdu M, Bagheri SM. Comparative effect of cinnamon essential oil, diclofenac and morphine on acute and chronic pain in mice. Int J Med Lab 2016; 3:92-103.
23. Amin B, Nakhsaz A, Hosseinzadeh H. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice. Avicenna J Phytomed 2015; 54:458-468.
24. Iravani S, Zolfaghari B. Phytochemical analysis of Pinus eldarica bark. Res Pharm Sci 2014; 9:243-250.
25. Friedman M, Kozukue N, Harden LA. Cinnamaldehyde content in foods determined by gas chromatography-mass spectrometry. J Agric Food Chem 2000; 48:5702-5709.
26. Borsini F, Meli A. Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology 1988; 94:147-160.
27. Cryan JF, Mombereau C, Vassout A. The tail suspension test as a model for assessing antidepre-ssant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev 2005; 29: 571-625.
28. Hegmann JP, DeFries JC. Open-field behavior in mice: Genetic analysis of repeated measures. Psychonomic Sci 1968; 13:27-28.
29. Pellow S, File SE. Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: A novel test of anxiety in the rat. Pharmacol Biochem Behav 1986; 24:525-529.
30. Bai F, Li X, Clay M, Lindstrom T, Skolnick P. Intra- and interstrain differences in models of "behavioral despair".Pharmacol Biochem Behav 2001; 70:187-192.
31. Uzun S, Kozumplik O, Jakovljevic M, Sedic B. Side effects of treatment with benzodiazepines. Psychiatria Danubina 2010; 22:90-93.
32. Rawdin BJ, Mellon SH, Dhabhar FS, Epel ES, Puterman E, Su Y, et al. Dysregulated relationship of inflammation and oxidative stress in major depression. Brain Behav Immun 2013; 31:143-152.
33. Salim S. Oxidative stress and psychological dis-orders. Curr Neuropharmacol 2014; 12:140-147.
34. Jayaprakasha GK, Rao LJ, Sakariah KK. Chemical composition of volatile oil from Cinnamomum zeylanicum buds. Z Naturforsch C 2002; 57:990-993.
35. Anderson RA, Broadhurst CL, Polansky MM, Schmidt WF, Khan A, Flanagan VP, et al. Isolation and characterization of polyphenol type-A polymers from cinnamon with insulin-like biological activity. J Agric Food Chem 2004; 52:65-70.
36. Park SY, Kim YH, Kim Y, Lee S-J. Aromatic-turmerone’s anti-inflammatory effects in microglial cells are mediated by protein kinase A and heme oxygenase-1 signaling. Neurochem Int 2012; 61:767-777.
37. Chen YF, Wang YW, Huang WS, Lee MM, Wood WG, Leung YM, et al. Trans-cinnamaldehyde, an essential oil in cinnamon powder, ameliorates cerebral ischemia-induced brain injury via inhibition of neuroinflammation through attenuation of iNOS, COX-2 expression and NFkappa-B signaling pathway. Neuromol Med 2016; 18:322-333.
38. Monroe SM, Slavish GM, Georgiades K. In: Hammen CL, Gotlib IH, editors. The social environment and life stress in depression. 2nd ed. New York: Guilford Press; 2009.
39. Iwasaki Y, Tanabe M, Kobata K, Watanabe T. TRPA1 agonists-allyl isothiocyanate and cinnamaldehyde-induce adrenaline secretion. Biosci Biotechnol Biochem 2008; 72:2608-2614.
40. Dorri SA, Hosseinzadeh H, Abnous K, Hasani FV, Robati RY, Razavi BM. Involvement of brain-derived neurotrophic factor (BDNF) on malathion induced depressive-like behavior in subacute exposure and protective effects of crocin. Iran J Basic Med Sci 2015; 18:958-966.
41. Jana A, Modi KK, Roy A, Anderson JA, van Breemen RB, Pahan K. Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: thera-peutic implications for neurodegenerative disorders. J Neuroimmune Pharmacol 2013; 8:739-755.
42. Isaac-Renton M, Li MK, Parsons LM. Cinnamon spice and everything not nice: many features of intraoral allergy to cinnamic aldehyde. Dermatitis 2015; 26:116-121.
43. Yilmaz Z, Piracha F, Anderson L, Mazzola N. Supplements for diabetes mellitus: A review of the literature. J Pharm Pract 2016 (in press).
44. Karyotaki E, Smit Y, Holdt Henningsen K, Huibers MJ, Robays J, de Beurs D, et al. Combining pharmacotherapy and psychotherapy or monotherapy for major depre-ssion? A meta-analysis on the long-term effects. J Affect Disord 2016; 194:144-152.
Iranian Journal of Basic Medical Sciences
Volume 20, Issue 6
June 2017
Pages 708-714

Files

Share

How to cite

Statistics