A review on antidepressant effect of medicinal plants

  • Zahra Rabiei Medical Plants Research Center, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.
  • Sana Rabiei Department of Fisheries, Faculty of Marine Sciences, Tarbiat Modares University, Noor, Iran.
Keywords: Antidepressant, Medicinal plant, Minireview
DOI: 10.3329/bjp.v12i1.29184


Depression is a life-threatening, debilitating, and common disease affecting different segments of community. Chemical and synthetic drugs available to treat this disease cause many adverse effects and may lead to complete recovery in only 50% of patients. At the same time, medicinal plants have been reported to exert optimal pharmacological effects in treating depression in different models. In this review, the relevant articles indexed in the reliable databases PubMed, PubMed central, Scopus and Web of Science were reviewed. The review indicated that most medicinal plants exerted antidepressant effects through synaptic regulation of serotonin, noradrenaline, and dopamine, regulating activity of hypothalamic-pituitary-adrenal axis, reinforcing antioxidant defense system, and decreasing inflammatory mediators. The medicinal plants and their active compounds can relieve depression through different pathways and hence are considered a new source to produce antidepressants.


Abbasi Maleki S, Bekhradi R, Asgharpanah J, Abbasi Maleki F and Maleki A. Antidepressant effect of aqueous and hydroalcoholic extracts of Lavandula officinalis in forced swim test and tail suspension test in male mice. J Arak Univ Med Sci. 2013; 16: 65-75.

Akhondzadeh S, Kashani L, Fotouhi A, Jarvandi S. Comparison of Lavandula angostofolia Mill. tincture and imipramine in the treatment of mild to moderate depression: A double-blind, randomized pilot study. Prog Neuropsychopharmacol Biol Psychiatry. 2003; 27: 123-27.

Akhondzadeh S, Tamacebipour N, Noorbala A, Amini H, Fallah Pour H, Jamshidi A. Crocus sativus L. in the treatment of mild to moderate depression: A double-blind, randomized and placebo controlled trial. Phytotherapy Res. 2005; 19: 25-29.

Alibabaei Z, Rabiei Z, Rahnama S, Mokhtari S, Rafieian-kopaei M. Matricaria chamomilla extract demonstrates antioxidant properties against elevated rat brain oxidative status induced by amnestic dose of scopolamine. Biomed Aging Pathol. 2014; 4: 355-60.

An L, Li J, Yu ST, Xue R, Yu NJ, Chen HX. Effects of the total flavonoid extract of Xiaobuxin-Tangon depression-like behavior induced by lipopolysaccharide and proinflammatory cytokine levels in mice. J Ethnopharmacol. 2015; 163: 83-87.

Avallone R, Zanoli P, Puia G, Kleinschnitz M, Chreier P, Baraldi M. Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla. Biochem Pharmacol. 2000; 59: 1387–94.

Babri S, Doosti M, Fatehi L, Salari A. The effects of Scrophularia striata extract on anxiety and depression behaviors in adult male mice. Pharm Sci. 2012; 18: 133-40.

Baradaran ARZ, Rafieian M, Shirzad H. A review study on medicinal plants affecting amnesia through cholinergic system. J Herb Med Pharmacol. 2012; 1: 3-9.

Barden N, Reul J, Holsboer F. Do antidepressants stabilize mood through actions on the hypothalamic-pituitary-adrenocortical system? Trends Neurosci. 1995; 18: 6–11.

Ban T. Pharmacotherapy of depression: A historical analysis. J Neural Transm . 2001; 108: 707-16.

Butterweck V. Mechanism of action of St John’s wort in depression. CNS Drugs. 2003; 17: 539-62.

Butterweck V, Korte B, Winterhoff H. Pharmacological and endocrine effects of Hypericum perforatum and hypericin after repeated treatment. Pharmacopsychiatry 2001; 34: 2-7.

Butterweck V, Schmidt M. St. John's wort: Role of active compounds for its mechanism of action and efficacy. Wien Med Wochenschr. 2007; 157: 356-61.

Carpenter C, Crigger N, Kugler R, Loya A. Hypericum and nurses: A comprehensive literature review on the efficacy of St. John's wort in the treatment of depression. J Holist Nurs. 2008; 26: 200-07.

Cassani J, Alberto Ferreyra-Cruz O, María Dorantes-Barrón A, Vigueras Villaseñor RM, Arrieta-Baez D, Estrada-Reyes R. Antidepressant-like and toxicological effects of a standardized aqueous extract of Chrysactinia mexicana A. Gray (Asteraceae) in mice. J Ethnopharmacol. 2015; 171: 295-306.

Chen CR, Tan R, Qu WM, Wu Z, Wang Y, Urade Y, Huang ZL. Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/ benzodiazepine receptor complex in mice. Br J Pharmacol. 2011; 164: 1534-46.

Colla ARS, Machado DG, Bettio LEB, Colla G, Magina MDA, Brighente IMC. Involvement of monoaminergic systems in the antidepressant-like effect of Eugenia brasiliensis Lam. (Myrtaceae) in the tail suspension test in mice. J Ethnopharmacol. 2012; 143: 720-31.

Cowburn R, Marcusson J, Eriksson A, Wiehager B, O'Neill C. Adenylyl cyclase activity and G-protein subunit levels in postmortem frontal cortex of suicide victims. Brain Res. 1994; 633: 297–304.

Dutcher JP, Logan T, Gordon M, Sosman J, Weiss G, Margolin K, Plasse T, Mier J, Lotze M, Clark J, Atkins M. Phase II trial of interleukin 2, interferon alpha, and 5-fluorouracil in metastatic renal cell cancer: A cytokine working group study. Clin Cancer Res. 2000; 6: 3442–50.

Farzin D, Fathiaza F, Fazellian M. Antidepressant effect of methanolic ginger extract in diabetic mice using forced-swim test. J Mazand Univ Med Sci. 2013; 23: 208-20.

Grundmann O, Lva Y, Kelber O, Butterweck V. Mechanism of St. John's wort extract (STW3-VI) during chronic restraint stress is mediated by the interrelationship of the immune, oxidative defense, and neuroendocrine system. Neuropharmacol. 2010; 58: 767-73.

Guadarrama-Cruz G, Alarcon-Aguilar FJ, Lezama-Velasco R, Vazquez-Palacios G, Bonilla-Jaime H. Antidepressant-like effects of Tagetes lucida Cav. in the forced swimming test. J Ethnopharmacol. 2008; 120: 277-81.

Guzmán-Gutiérrez SL, Bonilla-Jaime H, Gómez-Cansino R, Reyes-Chilpa R. Linalool and β-pinene exert their antidepressant-like activity through the monoaminergic pathway. Life Sci. 2015; 128: 24-29.

Harati E, Roodsari HRS, Seifi B, Kamalinejad M, Nikseresht S. The effect of oral Matricaria chamomilla extract and selenium on postpartum depression and plasma oxidant-antioxidant system in mice. Tehran Univ Med J. 2014; 71: 625-34.

Herrera-Ruiz M, García-Beltrán Y, Mora S, Díaz-Véliz G, Viana GS, Tortoriello J, Ramírez G. Antidepressant and anxiolytic effects of hydroalcoholic extract from Salvia elegans. J Ethnopharmacol. 2006; 107: 53–58.

Hu Z, Liu G, Cheng X, Huang Y, Yang S, Qiao S. JD-30 an active fraction extracted from Danggui-Shaoyao-San decreases beta-amyloid content and deposition, improves LTP reduction and prevents spatial cognition impairment in SAMP8 mice. Exp Gerontol. 2012; 47: 14-22.

Huang Z, Mao QQ, Zhong XM, Li ZY, Qiu FM. Mechanistic study on the antidepressant-like effect of Danggui-Shaoyao-San, a chinese herbal formula. Evid Based Complement Alternat Med. 2012; 12: 1-7.

Hwang J, Zheng LT, Ock J, Lee MG, Kim SH, Lee HW, Lee WH, Park HC and Suk K. Inhibition of glial inflammatory activation and neurotoxicity by tricyclic antidepressants. Neuropharmacol 2008; 55: 826–34.

Jäger A, Saaby L. Flavonoids and the CNS. Molecules 2011; 16: 1471-85.

Kou J, Zhu D, Yan Y. Neuroprotective effects of the aqueous extract of the Chinese medicine Danggui-Shaoyao-San on aged mice. J Ethnopharmacol. 2005; 97: 313–18.

Kuribara H, Stavinoha W, Maruyama Y. Behavioural pharmacological characteristics of honokiol, an anxiolytic agent present in extracts of Magnolia bark, evaluated by an elevated plus-maze test in mice. J Pharm Pharmacol Biochem Behav. 1998; 50: 819–26.

Kwon S, Lee B, Kim M, Lee H, Park HJ, Hahm DH. Antidepressant-like effect of the methanolic extract from Bupleurum falcatum in the tail suspension test. Prog Neuropsychopharmacol Biol Psychiatry. 2010; 34: 265-70.

Kamalipour M, Akhondzadeh S, Rezazadeh S. Herbal medicines in the treatment of depression and anxiety. J Med Plants. 2008; 7: 1-6.

Ladep NG, Obindo TJ, Audu MD, Okeke EN, Malu AO. Depression in patients with irritable bowel syndrome in Jos, Nigeria. World J Gastroenterol. 2006; 28: 7844-47.

Lai Z. Clinical application of Epimedium brevicornum. J Liaoning Coll Tradit Chin Med. 2001; 3: 266-73.

Lehmann E, Kinzler E, Friedemann J. Efficacy of a special kava extract (Piper methysticum) in patients with states of anxiety, tension and excitedness of non-mental origin: A double-blind placebo-controlled study of four weeks treatment. Phytomedicine 1996; 3: 113-19.

Li H, Gu Z, Wu L, Xia L, Zhou K, Wang D, Kou J, Liu H. Danggui-Shaoyao-San, a traditional Chinese medicine prescription, alleviates the orthodontic pain and inhibits neuronal and microglia activation. Chin Med J. 2014; 127: 3630–37.

Li Y, Gong Z, Zhang H, Luo Z. Effect of antidepressants on adenylate cyclase activity of rat cerebral cortex. Bull Acad Military Med Sci. 1999; 2: 18.

Linde K, Berner M, Kriston L. St John's wort for major depression. Cochrane Database Syst Rev. 2008; 8: 5-9.

Liu B, Xu C, Wu X, Liu F, Du Y, Sun J, Tao J, Dong J. Icariin exerts an antidepressant effect in an unpredictable chronic mild stress model of depression in rats and is associated with the regulation of hippocampal neuroinflammation. Neuroscience 2015; 294: 193-205.

Machado DG, Neis VB, Balen GO, Colla A, Cunha MP, Dalmarco JB. Antidepressant-like effect of ursolic acid isolated from Rosmarinus officinalis L. in mice: Evidence for the involvement of the dopaminergic system. Pharmacol Biochem Behav. 2012; 103: 204-11.

Machado DG, Kaster MP, Binfaré RW, Dias M, Santos ARS, Pizzolatti MG. Antidepressant-like effect of the extract from leaves of Schinus molle L. in mice: Evidence for the involvement of the monoaminergic system. Prog Neuropsycho-pharmacol Biol Psychiatry. 2007; 31: 421-28.

Machado DG, Bettio LEB, Cunha MP, Santos ARS, Pizzolatti MG, Brighente IMC. Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. in mice: Evidence for the involvement of the serotonergic and noradrenergic systems. Eur J Pharmacol. 2008; 587: 163-68.

Machado DG, Bettio LE, Cunha MP, Capra JC, Dalmarco JB, Pizzolatti MG, Rodrigues AL. Antidepressant-like effect of the extract of Rosmarinus officinalis in mice: Involvement of the monoaminergic system. Neuropsychopharmacol Biol Psychiatry. 2009; 33: 642-50.

Machado DG, Cunha MP, Neis VB, Balen GO, Colla A, Bettio LE, Oliveira A, Pazini FL, Dalmarco JB, Simionatto EL, Pizzolatti MG, Rodrigues AL. Antidepressant-like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L. Food Chem. 2013; 136: 999-1005.

Maes M, Galecki P, Chang Y, Berk M. A review on the oxidative and nitrosative stress (O & NS) pathways in major depression and their possible contribution to the (neuro) degenerative processes in that illness. Prog Neuropsycho-pharmacol Biol Psychiatry. 2011; 35: 676–92.

Menken M, Munsat T, Toole J. The global burden of disease study: Implications for neurology. Arch Neurol. 2000; 57: 418-20.

Menninger J, Tabakoff B. Forskolin-stimulated platelet adenylyl cyclase activity is lower in persons with major depression. Biol Psychiatry. 1997; 42: 30-38.

Mirzaei F, Keshtgar S, Kaviani M, Rajaeifard A. The effect of lavender ssence smelling during labor on cortisol and serotonin plasma levels and anxiety reduction in nulliparous women. J Kerman Univ Med Sci. 2009; 16: 245-54.

Mokhtari-Dehkordi S, Rouhi L, Rabiei Z. Effect of ethanolic extract of beet roots and leaves on motor coordination in male Wistar rats. J Shahrekord Univ Med Sci. 2014; 16: 108-15.

Nakazawa T, Yasuda T, Ohsawa K. Metabolites of orally administered Magnolia officinalis extract in rats and man and its antidepressant-like effects in mice. J Pharm Pharmacol. 2003; 55: 1583–91.

Pan Y, Kong LD, Li YC, Xia X, Kung HF, Jiang FX. Icariin from Epimedium brevicornum attenuates chronic mild stress-induced behavioral and neuroendocrinological alterations in male Wistar rats. Pharmacol Biochem Behav. 2007; 87: 130-40.

Pan Y, Kong L, Xia X, Zhang W, Xia Z, Jiang F. Antidepressant-like effect of icariin and its possible mechanism in mice. Pharmacol Biochem Behav. 2005; 82: 686-94.

Pandey G, Sharma R, Janicak P, Davis J. Monoamine oxidase and cortisol response in depression and schizophrenia. Psychiatry Res. 1992; 44: 1–8.

Pandya C, Howell K, Pillai A. Antioxidants as potential therapeutics for neuropsychiatric disorders. Prog Neuro-psychopharmacol Biol Psychiatry. 2013; 46: 214–23.

Plotsky PM, Owens MJ, Nemeroff CB. Psychoneuroendocrinology of depression: Hypothalamic-pituitary-adrenal axis. Psychiatr Clin North Am. 1998; 21: 293-307.

Qiu F, Zhong X, Mao Q, Huang Z. The antidepressant-like effects of paeoniflorin in mouse models. Exp Ther Med. 2013; 5: 1113-16.

Rabiei Z, Bigdeli M, Mohagheghi F, Rasolian B. Relationship between dietary virgin olive oil on brain cholesterol, cholesteryl ester and triglyceride levels and blood brain barrier (BBB) permeability in a rat stroke model. Physiol Pharmacol. 2012; 16: 245-54

Rabiei Z, Bigdeli MR, Rasoulian B. Neuroprotection of dietary virgin olive oil on brain lipidomics during stroke. Curr Neurovasc Res. 2013; 10: 231-37.

Rabiei Z, Bigdeli MR, Rasoulian B, Ghassempour A, Mirzajani F. The neuroprotection effect of pretreatment with olive leaf extract on brain lipidomics in rat stroke model. Phytomedicine 2012; 19: 940-46.

Rabiei Z, Bigdeli MR, Rasoulian B, Mohagheghi F, Sharifi A. The effect of various doses of olive leaf extract on brain lipid levels and blood brain barrier permeability in rat stroke model. Pajoohandeh J. 2012; 17: 67-72.

Rabiei Z, Gholami M, Hojjati M. The effect of Cyperus rotundus ethanolic extract on motor coordination in a rat model of alzheimer. ZUMS J. 2014; 22: 43-54.

Rabiei Z, Hojjati M, Rafieian-Kopaeia M, Alibabaei Z. Effect of cyperus rotundus tubers ethanolic extract on learning and memory in animal model of Alzheimer. Biomed Aging Pathol. 2013; 3: 185-91.

Rabiei Z, Rafieian-Kopaei M. Neuroprotective effect of pretreatment with Lavandula officinalis ethanolic extract on blood-brain barrier permeability in a rat stroke model. Asian Pac J Trop Med. 2014; 7: S421-26.

Rabiei Z, Rafieian-kopaei M, Heidarian E, Saghaei E, Mokhtari S. Effects of Zizyphus jujube extract on memory and learning impairment induced by bilateral electric lesions of the nucleus basalis of meynert in rat. Neurochem Res. 2014; 39: 353-60.

Rabiei Z, Rafieian-Kopaei M, Mokhtari S, Alibabaei Z, Shahrani M. The effect of pretreatment with different doses of Lavandula officinalis ethanolic extract on memory, learning and nociception. Biomed Aging Pathol. 2014; 4: 71-76.

Rabiei Z, Rafieian M. Effects of Zizyphus jujuba extract on motor coordination impairment induced by bilateral electric lesions of the nucleus basalis of meynert in rat. Physiol Pharmacol. 2014; 17: 469-77.

Rahnama S, Rabiei Z, Alibabaei Z, Mokhtari S, Rafieian-kopaei M, Deris F. Antiamnesic activity of citrus aurantium flowers extract against scopolamine-induced memory impairments in rats. Neurol Sci. 2014; 23: 1-8.

Richelson E. Pharmacology of antidepressants-characteristic of the ideal drug. Mayo Clin Proceed. 1994; 69: 1069-81.

Sukoff Rizzo SJ, Neal SJ, Hughes ZA, Beyna M, Rosenzweig-Lipson S, Moss SJ, Brandon NJ. Evidence for sustained elevation of IL-6 in the CNS as a key contributor of depressive-like phenotypes. Transl Psychiatry. 2012; 2: 199-208.

Saaby L, Rasmussen HB, Jager AK. MAO-A inhibitory activity of quercetin from Calluna vulgaris (L.) Hull J Ethnopharmacol. 2009; 121: 178-81.

Saki K, Bahmani M, Rafieian-Kopaei M. The effect of most important medicinal plants on two important psychiatric disorders (anxiety and depression): A review. Asian Pac J Trop Med. 2014; 7: 34-42.

Sasaki K, El Omri A, Kondo S, Han J, Isoda H. Rosmarinus officinalis polyphenols produce anti-depressant like effect through monoaminergic and cholinergic functions modulation. Behav Brain Res. 2013; 238: 86-94.

Seol GH, Shim HS, Kim PJ, Moon HK, Lee KH, Shim I, Suh SH, Min SS. Antidepressant-like effect of Salvia sclarea is explained by modulation of dopamine activities in rats. J Ethnopharmacol. 2010; 130: 187-90.

Shen Z, Chen Y, Huang J, Hu Z. The gene expression profile in hypothalamus-pituitary-adrenal-thymus (HPAT) axis from EF-treated old rats. Chin J Immunol. 2004; 20: 59–62.

Singer A, Schmidt M, Hauke W, Stade K. Duration of response after treatment of mild to moderate depression with Hypericum extract STW 3-VI, citalopram and placebo: A reanalysis of data from a controlled clinical trial. Phytomedicine 2011; 18: 739-42.

Song L, Che W, Wu M. Impairment of the spatial learning and memory induced by learned helplessness and chronic mild stress. Pharmacol Biochem Behav. 2006; 83: 186–93.

Tolardo R, Zetterman L, Bitencourtt DR, Mora TC, de Oliveira FL, Biavatti MW. Evaluation of behavioral and pharmacological effects of Hedyosmum brasiliense and isolated sesquiterpene lactones in rodents. J Ethnopharmacol. 2010; 128: 63-70.

Xing H, Zhang K, Zhang R, Zhang Y, Gu L, Shi H, Bi K, Chen X. Determination of depression biomarkers in rat plasma by liquid chromatography-mass spectrometry for the study of the antidepressant effect of Zhi-Zi-Hou-Po decoction on rat model of chronic unpredictable mild stress. J Chromatogr B. 2015; 988: 135-42.

Xu Q, Yi LT, Pan Y, Wang X, Li YC, Li JM, Wang CP, Kong LD. Antidepressant-like effects of the mixture of honokiol and magnolol from the barks of Magnolia officinalis in stressed rodents. Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32: 715-25.

Yabe T, Hirahara H, Harada N, Ito N, Nagai T, Sanagi T, Yamada H. Ferulic acid induces neural progenitor cell proliferation in vitro and in vivo. Neuroscience 2010; 165: 515–24.

Yao Y, Sang W, Yang X, Zhai M, Wang L, Qin P, Wu LI, Zhou X, Wang L, Li J, Zhu Z. Antidepressant effects of ginsenosides from Panax notoginseng. J Integr Agr. 2012; 3: 483–88.

Yu L, Zhang Y, Ma R, Bao L, Fang J, Yu T. Potent protection of ferulic acid against excitotoxic effects of maternal intragastric administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain. Eur Neuropsychopharmacol. 2006; 16: 170–77.

Zeni AL, Zomkowski AD, Maraschin M, Rodrigues AL, Tasca CI. Ferulic acid exerts antidepressant-like effect in the tail suspension test in mice: Evidence for the involvement of the serotonergic system. Eur J Pharmacol. 2012; 679: 68–74.

Zheng S, Yu M, Lu X, Huo T, Ge L, Yang J, Wu C, Li F. Urinary metabonomic study on biochemical changes in chronic unpredictable mild stress model of depression. Clin Chim Acta. 2010; 411: 204-09.

Zhong HB, Pan Y, Kong LD. Antidepressant effect of Epimedium brevicornum extracts. CTHD. 2005; 10: 34-40.

Zhou K, Jia N, Jiang N, Wang F, Kou J. Beneficial effect of Danggui-Shaoyao-San, a traditional Chinese medicine, on drowsiness induced by chronic restraint stress. Neurosci Lett. 2015; 597: 26-31


Apply citation style format of Bangladesh Journal of Pharmacology

Mini Review
Financial Support
Conflict of Interest
Authors declare no conflict of interest