Metabolic Brain Disease

, Volume 34, Issue 6, pp 1635–1647 | Cite as

Calotropis procera attenuates chronic unpredictable mild stress-induced depression in experimental animals

  • Debapriya GarabaduEmail author
  • Neha Srivastava
  • Yogesh Murti
Original Article


Calotropis procera (CP; Apocynaceae) is reported to have several neuroprotective activities however it’s anti-depressant activity yet to be established. Therefore, the present study was proposed to evaluate the anti-depressant activity of the standardized ethanolic extract of CP (ECP) in chronic unpredictable mild stress (CUMS) paradigm exposed male rats. Animals were exposed to CUMS from day-1 (D-1) to D-28 except control group animals of the experimental schedule. ECP (50, 100 and 200 mg/kg, p.o.) and Imipramin (15.0 mg/kg, p.o.) were administered for seven consecutive days after CUMS paradigm. On D-35, ECP (200 mg/kg) significantly attenuated immobility period of the animals in both forced-swim and tail suspension and improved behavioural parameters in open-field and anhedonia in sucrose feeding tests. ECP (200 mg/kg) attenuated CUMS-induced hyperactivity of HPA-axis function. Further, ECP (200 mg/kg) mitigated CUMS-induced decrease in serotonin (5-HT), increase in 5-hydroxy indole acetic acid (5-HIAA) and increase in the ratio of 5-HIAA/5-HT in hippocampus and pre-frontal cortex. The CUMS-induced decrease in the level of expression of BDNF was significantly reversed with ECP (200 mg/kg) treatment. Moreover, ECP (200 mg/kg) significantly reduced the CUMS-induced decrease in the mitochondrial function and integrity in terms of level of formazan formed and intensity of tetramethyl rhodamine methylester dye in both the brain regions respectively. Therefore, ECP (200 mg/kg) mitigates CUMS-induced alterations in the behaviours, HPA-axis function, serotonergic activity, neurogenesis and mitochondrial function in the rodents. Thus, it can be assumed that ECP could be a potential alternative candidate in the management of depression.


Calotropis procera Chronic unpredictable mild stress Corticosterone Serotonin Mitochondria Brain derived neurotrophic factor 



NS is thankful to GLA University, Mathura, Uttar Pradesh, India for the financial assistantship.

Compliance with ethical standards

All the experimental procedures utilized were performed in accordance with the approval of the Institutional Animal Ethics Committee (GLAIPR/CPCSEA/IAEC/2016/P.Col/R7) under strict compliance of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) guidelines for the experimental studies.

Conflict of interest

The authors declare that they have no conflict of interests.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Pharmacology, Institute of Pharmaceutical ResearchGLA UniversityMathuraIndia

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