Antidepressant activity of Spathodea campanulata in mice and predictive affinity of spatheosides towards type A monoamine oxidase

Jitendra Bajaj,Ram Sahu,Swapnil Sharma,Bhawana Sati,Abhay Prakash Mishra,Veronique Seidel,Sushil Joshi,Kanika Verma,Jaya Dwivedi,Vivek Dave

doi:10.14715/cmb/2021.67.1.1

Abstract

The antidepressant activity of Spathodea campanulata flowers was evaluated in mice and in silico. When tested at doses of 200 and 400 mg/kg, the methanol extract of S. campanulata (MESC) showed dose-dependent antidepressant activity in the force swim test (FST), tail suspension test (TST), lithium chloride-induced twitches test and the open field test. In FST and TST, animals treated with MESC demonstrated a significant decrease in the immobility period compared to the control group. The lithium chloride-induced head twitches were significantly reduced following administration of MESC. The latter, at the dose of 400 mg/kg, also significantly reduced locomotor activity. Following administration of MESC, changes in the levels of serum corticosterone, and of norepinephrine, dopamine, serotonin, 4-hydroxy-3-methoxyphenylglycol (MHPG), 4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in different brain regions using HPLC. The presence of spatheoside A (m/z 541) and spatheoside B (m/z 559) in MESC was detected using HPLC/ESI-MS. These two iridoids demonstrated a high predictive binding affinity for the active site of the type A monoamine oxidase (MAO-A) enzyme with scores of 99.40 and 93.54, respectively. These data suggest that S. campanulata flowers warrants further investigation as a source of novel templates for antidepressive drugs.

Highlights

Depression is a common and serious psychiatric disorder that is a major contributor to the global burden of disease
It has been reported that reactive oxygen species (ROS) and nitrogen species play an important part in the pathogenesis of depression by regulating the levels and activity of noradrenaline, serotonin, dopamine and glutamate, the principal neurotransmitters involved in the neurobiology of depression [2]
We evaluated the antidepressant activity of an ethyl acetate (EAESC) and a methanolic (MESC) extract from Spathodea campanulata flowers using pharmacological and computational approaches

Summary

Introduction

Depression is a common and serious psychiatric disorder that is a major contributor to the global burden of disease. It has been reported that reactive oxygen species (ROS) and nitrogen species play an important part in the pathogenesis of depression by regulating the levels and activity of noradrenaline (norepinephrine), serotonin, dopamine and glutamate, the principal neurotransmitters involved in the neurobiology of depression [2]. Several classes of antidepressant drugs (i.e. tricyclic antidepressants, selective serotonin reuptake inhibitors, selective reversible inhibitors of monoamine oxidase A, and specific serotonin–norepinephrine reuptake inhibitors) are used currently to treat depression a high number of side effects (e.g. sexual dysfunction) have been reported with these drugs and there is a need to discover an effective alternative treatment for depression that is better tolerated [3].

Methods

Results

Conclusion