The Effects of Cymbopogon citratus (lemon grass) on Morphine Withdrawal Signs in Male Mice

Hamed Ahmadi Sheikh-Sarmast, Saeid Abbasi-Maleki *

Abstract


Background and Aim: The antispasmodic, analgesic, antioxidant, anti-inflammatory and sedative effects of Cymbopogon citratus (C. citratus) have been already examined in various studies. Hence, the present study was conducted to investigate the effect of C. citratus hydroalcoholic extract on morphine withdrawal signs in male mice.

Materials and Methods: Male NMRI mice (20-30g) were rendered dependent by intraperitoneal (i.p.) injections of morphine three times daily at doses of 50, 50 and 75 mg/kg, respectively, for 3 days. After the last administration of morphine on the fourth day, different doses of C. citratus extract (140,280 and 560 mg/kg, i.p.) and clonidine (0.3mg/kg, i.p.) were administered 30 min before the administration of naloxone (5 mg/kg, i.p.). The mice were observed for 30 minutes for the withdrawal signs, i.e., the characteristic jumping, grooming, teeth chattering, climbing, rearing, wet dog shakes, writing and diarrhea.

Results: The findings revealed that all doses of C. citratus (p<0.01, p<0.001 and p<0.01, respectively) and clonidine (p<0.001) could reduce the number of jumps. Moreover, all doses of the extract reduced the grooming (p<0.05), climbing (p<0.05), diarrhea (p<0.01), and writhing behavior (p<0.05). Rearing and wet dog shakes were reduced only by the high dose of the extract (p<0.05).Clonidine decreased the other checked signs (except rearing and wet dog shake behaviors) such as grooming (P< 0.01), teeth chattering (P< 0.05), climbing (P<0.05), writing (P<0.01) and diarrhea (P<0.01).

Conclusion: The results indicated that C. citratus extract could attenuate morphine withdrawal signs. However, further studies are required to clarify its exact mechanism of action.


Keywords


Cymbopogon citrates, Morphine dependence, Naloxone, Withdrawal signs

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References


Hulse G K, English D R, Milne E, Holman CD. The quantification of mortality resulting from the regular use of illicit opiates. Addiction. 1999;94(2):221-9.

Bailey CP, Connor M. Opioids: cellular mechanisms of tolerance and physical dependence. Current Opinion in Pharmacology. 2005;5:60-8.

O’Connor PG. Methods of detoxification and their role in treating patients with opioid dependence. Journal of the American Medical Association. 2005; 294:961-3.

Espejo EF, Serrano MI, Caillé S, Stinus L.Behavioral expression of opiate withdrawal is altered after prefrontocortical dopamine depletion in rats: monoaminergic correlates. Neuropsychopharmacology. 2011;25(2):204-12.

Harris GC, Aston-Jones G. Beta-adrenergic antagonists attenuate somatic and aversive signs of opiate withdrawal. Neuropsychopharmacology. 1993; 9(4):303-11.

Rasmussen K, Krystal JH, Aghajanian GK. Excitatory amino acids and morphine withdrawal: differential effects of central and peripheral kynurenic acid administration. Psychopharmacology (Berl). 1991;105(4):508-12.

Hack SP, Vaughan CW, Christie MJ. Modulation of GABA release during morphine withdrawal in midbrain neurons in vitro. Neuropharmacology. 2003;45(5):575-84.

Abbasi-Maleki F, Abbasi-Maleki S, Mousavi SZ, Khayatnouri MH.Effect of hydroalcoholic extract of Avena sativa L. on morphine withdrawal signs in male mice. Quarterly Journal of Sabzevar University of Medical Sciences. 2014;20(4):408-15.

Abbasi-Maleki N, Abbasi-MalekiS, Bekhradi R. Suppressive Effects of Rosa Damascena Essential Oil on Naloxone- Precipitated Morphine Withdrawal Signs in Male Mice.Iranian Journal of Pharmaceutical Research. 2013;12(3): 357-61.

Abbasi Maleki S. Effect of ethanolic extract of Safflower on naloxone-induced morphine withdrawal signs in mice. Adv Herb Med. 2015;1(4):9-15.

Godarzi M, Abbasi Maleki S, Mousavi S Z, Moradi Kor N. Morphine withdrawal symptoms improvement by Ziziphora tenuior L. ethanoic extract in male mice. Koomesh. 2016;17(4):990-5.

Shirzadi D, Abbasi-Maleki S, Zanbouri A. Ethanolic extract of anise (Pimpinella anisum L.) attenuates morphine physical dependence in mice. J Herbmed Pharmacol. 2017;6(2):69-73.

Abdel-Zaher AO, Abdel-Rahman MS FM EL. Blockade of nitric oxide overproduction and oxidative stress byNigella sativa oil attenuates morphine-induced tolerance and dependence in mice. Neurochem Res. 2010;35(10):1557-65.

Raghavendra V, Rutkowski MD, DeLeo JA. The role of spinal neuroimmune activation in morphine tolerance/hyperalgesia in neuropathic and shamoperated rats. Journal of Neuroscience. 2002;22:9980-89.

Burkill IH. The useful plants of West Tropical Africa, Royal Botanic Garden, 1996;2:29-30.

Santin MR, Dos Santos AO, Nakamura, CV, Filh BPD, Ferreira ICP, Ueda-Nakamura T. In vitro activity of the essential oil of Cymbopogon citratus and its major component (citral) on Leishmania amazonensis. Parasitology Reserch Journal. 2009;105:1489-96.

Mirghani MES, LiyanaY, Parveen J. Bioactivity analysis of lemongrass (Cymbopogan citratus) essential oil. International Food Research Journal. 2012;19:569-75.

Mannelli P, Patkar A, Rozen S, Matson W, Krishnan R, Kaddurah-Daouk R. Opioid use affects antioxidant activity and purine metabolism: preliminary results. Human Psychopharmacolgy. 2009;24(8):666-75.

Uzama D. Phytochemical screening and antibacterial activity of garlic (Allium sativum L.) extracts. Environmental Science Journal Tropical. 2009;6(4):158-61.

Zarrindast MR, Malekzadeh A, Rezayat M, Ghazi-Khansari M. Effects of cholecytokinin receptor agonist and antagonists on morphine dependence in mice.Basic and Clinical Pharmacolgy and Toxicology. 1995;77:360-4.

Ghannadi A, Hajhashemi V, Abrishami R. Effects of the Persian Carum copticum fruit extracts on morphine withdrawal syndrome in mice. Research in Pharmaceutical Sciences. 2012;7(3):127-131.

Sepu lveda J, Astorga JG, Contreras, E. Riluzole decreases the abstinence syndrome and physical dependence in morphine dependent mice. European Journal of Pharmacology. 1999;379:59-62.

Caille S, Espejo EF, Reneric JP, Cador M, Koob, GF, Stinus L. Total neurochemical lesion of noradrenergic neurons of the locus coeruleus does not alter either naloxone-precipitated or spontaneous opiate withdrawal nor does it influence ability of clonidine to reverse opiate withdrawal. Journal of Pharmacology and Experimental Therapeutics. 1999;290:881-92.

Viana GSB, Vale TG, Pinho RSN, Matos FJA. Antinociceptive effect of the essential oil from Cymbopogon citratus in mice.Journal of Ethnopharmacology.2000; 70(3):323-7.

Blanco MM, Costa CARA, Freire AO, Santos JG Jr, Costa M. Neurobehavioral effect of essential oil of Cymbopogon citratus in mice. Phytomedicine.2009;16 : 265-70.

Shah G, Shri R, Panchal V, Sharma N, Singh B, Mann AS. Scientific basis for the therapeutic use of Cymbopogon citratus,staff (Lemongrass). Journal of advanced pharmaceutical technology and research. 2011;2(1):3-8.

Tangpu V, Yadav AK. Antidiarrhoeal activity of Cymbopogon citrates and its main constituent, citral. Pharmacologyonline. 2006;2:290-8.

Costa CA, Kohn DO, de Lima VM, Gargano AC, Florio JC, Costa M.(2011). The GABAergic system contributes to the anxiolytic-like effect of essential oil from Cymbopogon citratus (lemongrass). Journal of Ethnopharmacology. 2011;137:828-36.

Silva MR, Ximenes RM, da Costa JG, Leal LK, de Lopes AA, Viana GS.Comparative anticonvulsant activities of the essential oils (EOs) from Cymbopogon winterianus Jowitt and Cymbopogon citratus (DC) Stapf. in mice. Naunyn-Schmiedeberg's Archives of Pharmacology. 2011;381(5):415-26.

Jitka S, Zdenka D, Jiri N. Morphine as a Potential Oxidative Stress-Causing Agent. Mini -Reviews in Organic Chemistry. 2013;10:367-72.

Toda N, Kishioka S, Hatano Y, Toda H. Modulation of opioid actions by nitric oxide signaling. Anesthesiology. 2009;110(1):166-81.

Cappendijk SL, Duval SY, de Vries R, Dzoljic MR: Comparative study of normotensive and hypertensive nitric oxide synthase inhibitors on morphine withdrawal syndrome in rats. Neuroscience Letters. 1995;183:67-70.

Figueirinha A, Paranhos A, Perez-Alonso JJ, Santos-Buelga C, Batista MT. Cymbopogon citratus leaves: Characterisation of flavonoids by HPLC–PDA–ESI/MS/MS and an approach to their potential as a source of bioactive polyphenols. Food Chemistry. 2008;110:718-28.

Hutchinson MR, Lewis S, Coats B, Skyba D, Crysdale N, Berkelhammer D, Brzeski A. Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast). Brain, Behavior, and Immunity. 2009;23:240-50.

Francisco V, Figueirinha A, Neves BM, Garcia-Rodríguez C, Lopes MC, Cruz MT, Batista MT. Cymbopogon citratus as source of new and safe anti-inflammatory drugs: bio-guided assay using lipopolysaccharide-stimulated macrophages. Journal of Ethnopharmacology. 2011;133:818-27.

Quintans-Junior LJ, Guimaraes AG, Santana MT, Araujo BES, Moreira FV, Bonjardim LR, et al.Citral reduces nociceptive and inflammatory response in rodents. Brazilian Journal of Pharmacognosy. 2011;21:497-502.

Tiwari M, Dwivedi UN, Kakkar P.Suppression of oxidative stress and pro-inflammatory mediators by Cymbopogon citratus D. Stapf extract in lipopolysaccharide stimulated murine alveolar macrophages. Food and Chemical Toxicology. 2010;48:2913-9.




DOI: https://doi.org/10.22087/hmj.v3i1.677

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