Document Type : Original Article


1 Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

4 Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran


Background: Postpartum depression (PPD) is one type of major depression that has harmful effects on mother, infant and family relationships. Therefore, this study investigated the protective effects of hydro-alcoholic extract of Nigella sativa on PPD in mice.
Methods: In this experimental study, adult female mice were randomly divided into 6 groups (n=10): control, PPD, Nigella sativa 200, bicuculline, muscimol and fluoxetine. In all animals except in the control group, PPD was induced by progesterone withdrawal. In groups of Nigella sativa 200, bicuculline, muscimol and fluoxetine, mice received 200 mg/kg Nigella sativa, 1 mg/kg bicuculline + 200 mg/kg Nigella sativa, 0.5 mg/kg muscimol and 15 mg/kg fluoxetine, respectively. Then, after 1 hr, the forced swimming test and open field test was examined.
Results: PPD caused significant increases in the immobility times in the forced swimming test (P < 0.05). Administration of Nigella sativa, muscimol and fluoxetine attenuated depression-related behaviors in compared to the PPD group (all P < 0.05). However, combined administration bicuculline with Nigella sativa prevented antidepressant effects of this extract. Moreover, there were no significant differences in the crossing number in the open field test of all groups.
Conclusions: Administration of Nigella sativa hydro-alcoholic extracts can be beneficial to the improvement in PPD and exerts possibly these protective effects partially through increase of gamma amino butyric acid (GABA)-A levels.

Graphical Abstract

Nigella Sativa Hydro-Alcoholic Extract Attenuates Postpartum Depression Through Increase of Gamma Amino Butyric Acid-A Levels


Main Subjects

2. Slomian J, Honvo G, Emonts P, Reginster JY, Bruyere O. (2019). Consequences of maternal postpartum depression: A systematic review of maternal and infant outcomes. Women's Health., 15:1745506519844044.
3. Meky HK, Shaaban MM, Ahmed MR, Mohammed TY. (2019). Prevalence of postpartum depression regarding mode of delivery: a cross-sectional study. J. Matern. Fetal. Neonatal. Med., 1-8.
4. Jahangard L, Mikoteit T, Bahiraei S, Zamanibonab M, Haghighi M, Sadeghi-Bahmani D, Brand S. (2019). Prenatal and postnatal hair steroid levels predict post-partum depression 12 weeks after delivery. J. Clin. Med., 8(9):1290.
5. Payne JL, Maguire J. (2019). Pathophysiological mechanisms implicated in postpartum depression. Front. Neuroendocrinol., 52:165-180.
6. Wang SM, Han C, Bahk WM, Lee SJ, Patkar AA, Masand PS, Pae CU. (2018). Addressing the side effects of contemporary antidepressant drugs: a comprehensive review. Chonnam. Med. J., 54(2):101-12.
7. Yimer EM, Tuem KB, Karim A, Ur-Rehman N, Anwar F. (2019). Nigella sativa L. (black cumin): a promising natural remedy for wide range of illnesses. Evid. Based. Complement. Alternat. Med., 2019:1528635.
8. Gholamnezhad Z, Shakeri F, Saadat S, Ghorani V, Boskabady MH. (2019). Clinical and experimental effects of Nigella sativa and its constituents on respiratory and allergic disorders. Avicenna. J. Phytomed., 9(3):195-212.
9. Ahirwar D, Ahirwar B. (2020). Antidepressant effect of Nigella sativa in stress-induced depression. Res. J. Pharm. Technol., 13(4):1611-1614.
10. Elkhayat ES, Alorainy MS, El-Ashmawy IM, Fat’hi S. (2016). Potential antidepressant constituents of Nigella sativa seeds. Pharmacogn. Mag., 12:S27-31.
11. Hosseini M, Zakeri S, Khoshdast S, Yousefian FT, Rastegar M, Vafaee F, Kahdouee S, Beckley EH, Finn DA. (2007). Inhibition of progesterone metabolism mimics the effect of progesterone withdrawal on forced swim test immobility. Pharmacol. Biochem. Behav., 87(4):412-419.
12. Xu J, Kurup P, Nairn AC, Lombroso PJ. (2018). Synaptic NMDA Receptor Activation Induces Ubiquitination and Degradation of STEP 61. Mol. Neurobiol., 55(4):3096-3111.
13. Kitamura Y, Hongo S, Yamashita Y, Yagi S, Otsuki K, Miki A, Okada A, Ushio S, Esumi S, Sendo T. (2019). Influence of lipopolysaccharide on diazepam-modified loss of righting reflex duration by pentobarbital treatment in mice. Eur. J. Pharmacol., 842:231-238.
14. Arbabi L, Baharuldin MTH, Moklas MAM, Fakurazi S, Muhammad SI. (2014). Antidepressant-like effects of omega-3 fatty acids in postpartum model of depression in rats. Behav. Brain. Res., 271:65-71.
15. Porsolt R, Bertin A, Jalfre M. (1977). Behavioral despair in mice: a primary screening test for antidepressants. Arch. Int. Pharmacodyn. Ther., 229(2):327-336.
16. Seibenhener ML, Wooten MC. (2015). Use of the open field maze to measure locomotor and anxiety-like behavior in mice. J. Vis. Exp., 96:e52434.
17. Harati E, Sadeghipour -Roodsari HR, Seifi B, Kamalinejad M, Nikseresht S. (2014). The effect of oral Matricaria Chamomilla extract and selenium on postpartum depression and plasma oxidant-antioxidant system in mice. TUMJ., 71(10):625-634.
18. El-Naggar T, Gomez-Serranillos MP, Palomino OM,  Arce C, Carretero ME. (2010). Nigella sativa L. seed extract modulates the neurotransmitter amino acids release in cultured neurons in vitro. J. Biomed. Biotechnol., 2010:398312.