EFFECTS OF CINNAMOMUM ZEYLANICUM BARK EXTRACT ON NOCICEPTION AND ANXIETY LIKE BEHAVIOR IN MICE
Objectives: The aim of the study was to assess the effect of the extract of Cinnamomum zeylanicum (CZ) bark in the experimental models of pain and anxiety-like behavior in mice.
Methods: The extract of CZ bark was administered at the doses of 100, 200, and 400 mg/kg, per orally (p.o) and morphine used as a positive control for pain models, was administered at the dose of 5 mg/kg, intraperitoneally (i.p.). Antinociceptive activity was evaluated using three experimental animal models of pain, namely, tail flick, hot plate, and formalin test. Elevated plus maze test was used to assess the effect on anxiety-like behavior. Rotarod apparatus and actophotometer were used to test muscle coordination and locomotor activity, respectively.
Results: Administration of CZ bark extract in the dose of 200 and 400 mg/kg showed significantly increased in the tail-flick latency and latency to reaction time in hot plate test as compared to the control group. In the first phase (0–5 min) of the formalin test, a significant reduction in the pain response was found in CZ (200 and 400 mg/kg) and morphine-treated groups, however during the second phase (30–35 min) significant reduction in formalin-induced pain response was observed in 100, 200, and 400 mg/kg CZ extract-treated group when compared to control group. CZ extract administration at 200 and 400 mg/kg dose caused a significant increase in the percentage of time spent in open arms in the elevated plus maze as compared to the control group.
Conclusion: Results suggest that CZ bark extract possesses the antinociceptive activity and modulates anxiety-like behavior.
2. Aneja K, Joshi R, Sharma C. Antimicrobial activity of dalchini (Cinnamomum zeylanicum bark) extracts on some dental caries pathogens. J Pharm Res 2009;2:1387-90.
3. Chao LK, Hua KF, Hsu HY, Cheng SS, Liu JY, Chang ST. Study on the antiinflammatory activity of essential oil from leaves of Cinnamomum osmophloeum. J Agric Food Chem 2005;53:7274-8.
4. Ravindran PN, Nirmal-Babu K, Shylaja M. Cinnamon and Cassia: The genus Cinnamomum. Danvers, MA: CRC Press; 2003.
5. López P, Sánchez C, Batlle R, Nerín C. Solid- and vapor-phase antimicrobial activities of six essential oils: Susceptibility of selected foodborne bacterial and fungal strains. J Agric Food Chem 2005;53:6939-46.
6. Dongmo PM, Tatsadjieu LN, Tchoumbougnang F, Sameza ML, Ndongson B, Zollo PH, et al. Chemical composition, antiradical and antifungal activities of essential oil of the leaves of Cinnamomum zeylanicum Blume from Cameroon. Nat Prod Commun 2007;12:1287-90.
7. Kurokawa M, Kumeda CA, Yamamura J, Kamiyama T, Shiraki K. Antipyretic activity of cinnamyl derivatives and related compounds in influenza virus-infected mice. Eur J Pharmacol 1998;348:45-51.
8. Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with Type 2 diabetes. Diabetes Care 2003;26:3215-8.
9. Lee JS, Jeon SM, Park EM, Huh TL, Kwon OS, Lee MK, et al. Cinnamate supplementation enhances hepatic lipid metabolism and antioxidant defense systems in high cholesterol-fed rats. J Med Food 2003;6:183-91.
10. Jayaprakasha GK, Ohnishi-Kameyama M, Ono H, Yoshida M, Jaganmohan Rao L. Phenolic constituents in the fruits of Cinnamomum zeylanicum and their antioxidant activity. J Agric Food Chem 2006;54:1672-9.
11. Soliman KM, Badeaa RI. Effect of oil extracted from some medicinal plants on different mycotoxigenic fungi. Food Chem Toxicol 2002;40:1669-75.
12. 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.
13. Jain S, Sangma T, Shukla SK, Mediratta PK. Effect of Cinnamomum zeylanicum extract on scopolamine-induced cognitive impairment and oxidative stress in rats. Nutr Neurosci 2015;18:210-6.
14. Shaughnessy DT, Setzer RW, DeMarini DM. The antimutagenic effect of vanillin and cinnamaldehyde on spontaneous mutation in salmonella TA104 is due to a reduction in mutations at GC but not AT sites. Mutat Res 2001;480-481:55-69.
15. Stavinoha RC, Vattem DA. Potential neuroprotective effects of cinnamon. Int J Appl Res Nat Prod 2015;8:24-46.
16. Tomaino A, Cimino F, Zimbalatti V, Venuti V, Sulfaro V, De Pasquale V, et al. Influence of heating on antioxidant activity and the chemical composition of some spice essential oils. Food Chem 2005;89:549-54.
17. 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-kappa B activation in RAW 264.7 cells. Biochem Pharmacol 2005;69:791-9.
18. Fu Y, Yang P, Zhao Y, Zhang L, Zhang Z, Dong X, et al. Trans-cinnamaldehyde inhibits microglial activation and improves neuronal survival against neuroinflammation in BV2 microglial cells with lipopolysaccharide stimulation. Evid Based Complement Alternat Med 2017;2017:4730878.
19. Joshi K, Awte S, Bhatnagar P, Walunj S, Gupta R, Joshi S, et al. Cinnamomum zeylanicum extract inhibits proinflammatory cytokine TNF: In vitro and in vivo studies. Res Pharm Biotech 2010;2:14-21.
20. Dashti-R MH, Qane MD, Shefaie F, Yazdu MN, 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.
21. Churihar R, Solanki P, Vyas S, Tanwani H, Atal S. Analgesic activity of cinnamaldehyde per se and it’s interaction with diclofenac sodium and pentazocine in Swiss albino mice. Int J Phamacol 2016;3:97-102.
22. Izadpanah E, Nikandam F, Moloudi MR, Hassanzadeh K. Evaluation of the analgesic effect of hydroalcoholic extract of Cinnamomum in rats. Sci J Kurdistan Univ Med Sci 2016;21:1-8.
23. Atta AH, Alkofahi A. Anti-nociceptive and anti-inflammatory effects of some Jordanian medicinal plant extracts. J Ethnopharmacol 1998;60:117-24.
24. Trease EG, Evans WC. Textbook of Pharmacognosy. 12th ed. Singapore: Alden Press; 1983. p. 539-41.
25. D’Amour FE, Smith DL. A method for determining loss of pain sensation. J Pharmacol Exp Ther 1941;72:74-9.
26. Pires JM, Mendes FR, Negri G, Duarte-Almeida JM, Carlini EA. Antinociceptive peripheral effect of Achillea millefolium L. And Artemisia vulgaris L.: Both plants known popularly by brand names of analgesic drugs. Phytother Res 2009;23:212-9.
27. Abbott FV, Franklin KB, Westbrook RF. The formalin test: Scoring properties of the first and second phases of the pain response in rats. Pain 1995;60:91-102.
28. Kulkarni SK, Dandiya PC. Influence of intraventricular administration of norepinephrine, dopamine and 5-hydroxytryptamine on motor activity of rats. Indian J Med Res 1975;63:462-8.
29. Bharal N, Sahaya K, Jain S, Mediratta PK, Sharma KK. Curcumin has anticonvulsant activity on increasing current electroshock seizures in mice. Phytother Res 2008;22:1660-4.
30. Abdel-Salam OM, Baiuomy AR, Nada SA. Effect of spironolactone on pain responses in mice. EXCLI J 2010;9:46-57.
31. Dunham NW, Miya TS. A note on a simple apparatus for detecting neurological deficit in rats and mice. J Am Pharm Assoc Am Pharm Assoc 1957;46:208-9.
32. Pellow S, Chopin P, File SE, Briley M. Validation of open: Closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 1985;14:149-67.
33. Torizuka K. Basic lecture of kampo medicine: Pharmacological effect of cinnamon. Kampo Med 1998;11:431-6.
34. Sachan AK, Kumar S, Kumari K, Singh D. Medicinal uses of spices used in our traditional culture: Worldwide. J Med Plants 2018;6:116-22.
35. AL-Logmani AS, Zari TA. Effects of Nigella sativa L. and Cinnamomum zeylanicum Blume oils on some physiological parameters in streptozotocin-induced diabetic rats. Bol Latinoam Caribe Plantas Med Aromát 2009;8:86-96.
36. Dhuley JN. Anti-oxidant effects of cinnamon (Cinnamomum verum) bark and greater cardamom (Amomum subulatum) seeds in rats fed high fat diet. Indian J Exp Biol 1999;37:238-42.
37. Kim SH, Hyun SH, Choung SY. Anti-diabetic effect of cinnamon extract on blood glucose in db/db mice. J Ethnopharmacol 2006;104:119-23.
38. Kannappan S, Jayaraman T, Rajasekar P, Ravichandran MK, Anuradha CV. Cinnamon bark extract improves glucose metabolism and lipid profile in the fructose-fed rat. Singapore Med J 2006;47:858-63.
39. Kwon HK, Hwang JS, Lee CG, So JS, Sahoo A, Im CR, et al. Cinnamon extract suppresses experimental colitis through modulation of antigen-presenting cells. World J Gastroenterol 2011;17:976-86.
40. Hasan SR, Mariam J, Majumder MM, Raushanara A, Hossain MM, Mazumder M, et al. Analgesic and antioxidant activity of the hydromethanolic extract of Mikania scandens (L.) Willd. Leaves. Am J Pharmacol Toxicol 2009;4:1-7.
41. Mansouri MT, Naghizadeh B, Ghorbanzadeh B. Sildenafil enhances the peripheral antinociceptive effect of ellagic acid in the rat formalin test. Indian J Pharmacol 2014;46:404-8.
42. Sinclair JG, Main CD, Lo GF. Spinal vs. Supraspinal actions of morphine on the rat tail-flick reflex. Pain 1988;33:357-62.
43. Sridharan S, Venkatramani M, Janakiraman K, Pemiah B, Chinnagounder S. Barleria Montana wight and Nees a promising natural anti-inflammatory agent against formalin induced inflammation. Int J Pharm Pharm Sci 2015;7:80-4.
44. Shibata M, Ohkubo T, Takahashi H, Inoki R. Modified formalin test: Characteristic biphasic pain response. Pain 1989;38:347-52.
45. Song F, Li H, Sun J, Wang S. Protective effects of cinnamic acid and cinnamic aldehyde on isoproterenol-induced acute myocardial ischemia in rats. J Ethnopharmacol 2013;150:125-30.
46. Chao LK, Hua KF, Hsu HY, Cheng SS, Lin IF, Chen CJ, et al. Cinnamaldehyde inhibits pro-inflammatory cytokines secretion from monocytes/macrophages through suppression of intracellular signaling. Food Chem Toxicol 2008;46:220-31.
47. Zeashan H, Amresh G, Rao CV, Singh S. Antinociceptive activity of Amaranthus spinosus in experimental animals. J Ethnopharmacol 2009;122:492-6.
48. Nguyen TT, Matsumoto K, Yamasaki K, Nguyen MD, Nguyen TN, Watanabe H, et al. Crude saponin extracted from vietnamese ginseng and its major constituent majonoside-R2 attenuate the psychological stress- and foot-shock stress-induced antinociception in mice. Pharmacol Biochem Behav 1995;52:427-32.
49. Hacimuftuoglu A, Handy CR, Goettl VM, Lin CG, Dane S, Stephens RL Jr., et al. Antioxidants attenuate multiple phases of formalin-induced nociceptive response in mice. Behav Brain Res 2006;173:211-6.
50. 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;31:143-52.
51. Salim S. Oxidative stress and psychological disorders. Curr Neuropharmacol 2014;12:140-7.
52. Sohrabi R, Pazgoohan N, Seresht HR, Amin B. Repeated systemic administration of the cinnamon essential oil possesses anti-anxiety and anti-depressant activities in mice. Iran J Basic Med Sci 2017;20:708-14.
53. Fadaei S. Asle-Rousta M. Anxiolytic and antidepressant effects of cinnamon (Cinnamomum verum) extract in rats receiving lead acetate. Sci J K Univ 2018;22:31-9.
54. Yu HS, Lee SY, Jang CG. Involvement of 5-HT1A and GABAA receptors in the anxiolytic-like effects of Cinnamomum cassia in mice. Pharmacol Biochem Behav 2007;87:164-70.
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