Anti-depressant Activity of Hydroalcoholic Extract of Asperula odorata L. in Mice

  • Mohammad Amin Hatami Nemati 1. Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  • Kimia Vatani 1. Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  • Zahra Abbasy 2. Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
  • Mahsa Hadipour Jahromy 3. Herbal Pharmacology Research Center Department of Pharmacology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  • Poorya Davoodi 4. Department of Molecular Medicine, University of Padua, Padua, Italy
Keywords: Anti-Depressant, Flavonoid, Asperula Odorata L., Monoamine Oxidase, Mice


Background: The relationship between the treatment of depression and plant-derived substances (e.g., flavonoids, coumarin, and scopoletin) has been demonstrated through interference with the monoamine system. The present study was planned to evaluate the anti-depressant effects of Asperula odorata L. plant through behavioral tests in mice. Material and Methods: In this experimental study, 35 male Syrian mice weighing 30-40 g were examined in five groups (n=7) as follow: received oral distilled water gavage (control), 10 mg/kg of fluoxetine solution gavage (reference standard), 10, 5, and 2.5 mg/kg of A. odorata L. extract gavage (treatment groups). After one week, all behavioral tests, including tail suspension test (TST), forced swimming test (FST), open field test (OFT), elevated plus maze test (EPMT), and fractionation tests were performed each morning for 4-6 h within five days. Results: The hydroalcoholic extract of A. odorata contained phenolic and flavonoid substances (Shinoda test confirmed flavonoid family). Administration of extract (10 and 5 mg/kg doses) versus fluoxetine (10 mg/kg dose) reduced the immobility of animals in both FST and TST (P<0.05). At the OFT, the administered extract increased the number of central square entries of animals with higher mobility (P<0.05). At a 10 mg/kg dose, the active flavonoid ingredients increased the mice's incline to entre and spent more time within no wall parts of EPMT (P<0.05). Conclusion: Our study suggests that the hydroalcoholic extract of A. odorata L. could have significant anti-depressant activity. [GMJ.2021;10:e2206]


Yi LT, Li CF, Zhan X, Cui CC, Xiao F, Zhou LP, Xie Y. Involvement of monoaminergic system in the antidepressant-like effect of the flavonoid naringenin in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2010; 34(7): 1223-8.


Zavvari F, Karimzadeh F. A methodological review of development and assessment of behavioral models of depression in rats. Neurosci J Shefaye Khatam. 2015;3(4):151-60.

Wu CS, Yu SH, Lee CY, Tseng HY, Chiu YF, Hsiung CA. Prevalence of and risk factors for minor and major depression among community-dwelling older adults in Taiwan. Int Psychogeriatr. 2017;29(7):1113-21.


Capra JC, Cunha MP, Machado DG, Zomkowski AD, Mendes BG, Santos AR, Pizzolatti MG, Rodrigues AL. Antidepressant-like effect of scopoletin, a coumarin isolated from Polygala sabulosa (Polygalaceae) in mice: evidence for the involvement of monoaminergic systems. Eur J Pharmacol. 2010;643(2-3): 232-8.


Riolo SA, Nguyen TA, Greden JF, King CA. Prevalence of depression by race/ethnicity: findings from the National Health and Nutrition Examination Survey III. Am J Public Health. 2005; 95(6): 998-1000.

PMid:15914823 PMCid:PMC1449298

Lehtinen V, Joukamaa M. 1994. Epidemiology of depression: prevalence, risk factors and treatment situation. Acta Psychiatr Scand. 1994; 89:7-10.


Simon GE, Goldberg DP, Von Korff M, Ustün TB. Understanding cross-national differences in depression prevalence. Psychol Med. 2002;32(4):585-94.


Pérez JH, Furlow JD, Wingfield JC, Ramenofsky M. Regulation of vernal migration in Gambel's white-crowned sparrows: role of thyroxine and triiodothyronine. Horm Behav. 2016; 84:50-6.


Sarokhani D, Parvareh M, Hasanpour Dehkordi A, Sayehmiri K, Moghimbeigi A. Prevalence of Depression among Iranian Elderly: Systematic Review and Meta-Analysis. Iran J Psychiatry. 2018;13(1):55-64.

Mahmoudi F, Gollo KH. Influences of Serotonin Hydrochloride on Adiponectin, Ghrelin and KiSS1 Genes Expression. GMJ. 2020;9:e1767.

PMid:34466589 PMCid:PMC8343906

Adalat M, Khalili M, Ayromlou H, Haririan S, Fazljou SM, Rezaeizadeh H, Safari AA, Zargaran A. Antidepressant Effects of a Persian Medicine Remedy on Multiple Sclerosis Patients: A Double-Blinded Randomized Clinical Trial. GMJ. 2019;8:e1212.

Ernst E, Rand JI, Barnes J, Stevinson C. Adverse effects profile of the herbal anti-depressant St. John's wort (Hypericum perforatum L.). Eur J Clin Pharmacol. 1998;54(8):589-94.


Yurchenko NS, Il TV, Kovaleva AM. Amino-Acid Composition of Asperula odorata Herb. Chem Nat Compd. 2013;49(2):401-2.

Sergeevna IN, Mihaylovna KA, Leonidivna TE, Aleksandrovna KI. The Antihypoxic and Sedative Activity of the Dry extract from Asperula odorata L. Pharmacogn. Commun. 2015;5(4):233-6.

Guan LP, Liu BY. Antidepressant-like effects and mechanisms of flavonoids and related analogues. Eur J Med Chem. 2016; 121:47-57.


Mattioli L, Funari C, Perfumi M. Effects of Rhodiola rosea L. extract on behavioural and physiological alterations induced by chronic mild stress in female rats. J Psychopharmacol. 2009;23(2):130-42.


Vazquez-Palacios G, Bonilla-Jaime H, Velazquez-Moctezuma J. Antidepressant-like effects of the acute and chronic administration of nicotine in the rat forced swimming test and its interaction with flouxetine. Pharmacol Biochem Behav. 2004;78(1):165-9.


Costa AP, Vieira C, Bohner LO, Silva CF, da Silva Santos EC, De Lima TC, et al. A proposal for refining the forced swim test in Swiss mice. Prog Neuropsychopharmacol Biol Psychiatry. 2013;45:150-5.


Page ME, Detke MJ, Dalvi A, Kirby LG, Lucki I. Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test. Psychopharmacology. 1999;147(2):162-7.


Chen PJ, Hsieh CL, Su KP, Hou YC, Chiang HM, Lin IH, et al. The antidepressant effect of Gastrodia elata Bl. on the forced-swimming test in rats. Am J Chinese Med. 2008;36(01):95-106.


Kudryashov NV, Kalinina TS, Shimshirt AA, Korolev AO, Volkova AV, Voronina TA. Antidepressant-like effect of fluoxetine may depend on translocator protein activity and pretest session duration in forced swimming test in mice. Behav Pharmacol. 2018;29(4):375-8.


Osanloo N, Najafi-Abedi A, Jafari F, Javid F, Pirpiran M, Jafari MR, et al. Papaver rhoeas L. hydroalcoholic extract exacerbates forced swimming test-induced depression in mice. Basic Clin Neurosci. 2016;7(3):195.

PMid:27563412 PMCid:PMC4981831

Szymczyk G, Zebrowska-Lupina I. Influence of antiepileptics on efficacy of antidepressant drugs in forced swimming test. Pol J Pharmacol. 2000;52(5):337-44.

Haj-Mirzaian A, Kordjazy N, Ostadhadi S, Amiri S, Haj-Mirzaian A, Dehpour A. Fluoxetine reverses the behavioral despair induced by neurogenic stress in mice: role of N-methyl-d-aspartate and opioid receptors. Can J Physiol Pharmacol. 2016;94(6):599-612.


Petit-Demouliere B, Chenu F, Bourin M. Forced swimming test in mice: a review of anti-depressant activity. Psychopharmacol. 2005;177(3):245-55.


Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening anti-depressants in mice. Psychopharmacol. 1985; 85(3):367-70.


Carola V, D'Olimpio F, Brunamonti E, Mangia F, Renzi P. Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice. Behav Brain Res. 2002;134(1-2):49-57.

Hellión-Ibarrola MC, Ibarrola DA, Montalbetti Y, Kennedy ML, Heinichen O, Campuzano M, et al. The antidepressant-like effects of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) in mice. Phytomedicine. 2008;15(6-7):478-83.


Rabiei, Z, Rabiei S, A review on antidepressant effect of medicinal plants. Bangladesh Journal of Pharmacology. 2017. 12(1): 1-11.

Friedrich MJ, Depression is the leading cause of disability around the world. Jama. 2017;317(15):1517.

Eloziia N, Kumar N, Kothiyal P, Deka P, Nayak BK. A Review on Antidepressant Plants. Journal of Pharmacy Research. 2017;11(5):382-96.

Gamasaee NA, Radmansouri M, Ghiasvand S, Shahriari F, Marzouni HZ, et al. Hypericin induces apoptosis in MDA-MB-175-VII cells in lower dose compared to MDA-MB-231. Archives of Iranian medicine. 2018;21(9):387-92.

Duman RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry, 1997;54(7):597-606.


Alcocer-Gomez E, Cordero MD. NLRP3 inflammasome: a new target in major depressive disorder. CNS Neurosci Ther. 2014;20(3):294-5.

PMid:24479787 PMCid:PMC6493047

Verkhratsky A, Rodriguez JJ, Steardo L. Astrogliopathology: a central element of neuropsychiatric diseases? Neuroscientist. 2014;20(6):576-88.


Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009;8(8):627-44.

PMid:19644473 PMCid:PMC3142564

Yi LT, Liu BB, Li J, Luo L, Liu Q, Geng D, et al. BDNF signaling is necessary for the antidepressant-like effect of naringenin. Prog Neuropsychopharmacol Biol Psychiatry. 2014;48:135-41.


Yi LT, Li J, Li HC, Su DX, Quan XB, He XC, et al. Antidepressant-like behavioral, neurochemical and neuroendocrine effects of naringenin in the mouse repeated tail suspension test. Prog Neuropsychopharmacol Biol Psychiatry. 2012;39(1):175-81.


Zhang H, Xue W, Wu R, Gong T, Tao W, Zhou X, et al. Rapid antidepressant activity of ethanol extract of Gardenia jasminoides Ellis is associated with upregulation of BDNF expression in the hippocampus. Evid Based Complement Alternat Med. 2015.

PMid:25878718 PMCid:PMC4387974

Zhou XJ, Liu M, Yan JJ, Cao Y, Liu P. Antidepressant-like effect of the extracted of Kai Xin San, a traditional Chinese herbal prescription, is explained by modulation of the central monoaminergic neurotransmitter system in mouse. J Ethnopharmacol. 2012;139(2):422-8.


Bowen IH, Corrigan D, Cubbin IJ, de Smet PA, Hänsel R, Sonnenborn U, et al. Adverse Effects of Herbal Drugs 2. Springer Science & Business Media. 2012.

How to Cite
Hatami Nemati, M. A., Vatani, K., Abbasy, Z., Hadipour Jahromy, M., & Davoodi, P. (2021). Anti-depressant Activity of Hydroalcoholic Extract of Asperula odorata L. in Mice. Galen Medical Journal, 10, e2206.
Original Article