Comparative evaluation of natural neuroprotectives and their combinations on chronic immobilization stress-induced depression in experimental mice.

The present study evaluates the potential of neuroprotective phytochemicals-rutin (R), resveratrol (Res), 17β-estradiol (17β-E2), and their different combinations against chronic immobilization stress (CIS)-induced depression-like behaviour in male albino mice. Here, the mice were exposed to stress via immobilization of their four limbs under a restrainer for 6 h daily until 7 days of the induction after 30 min of respective drug treatment in different mice groups. The result found the protective effect of these phytoconstituents and their combinations against CIS-induced depression due to their ability to suppress oxidative stress, restore mitochondria, HPA-axis modulation, neurotransmitter level, stress hormones, and inflammatory markers. Also, the combination drug regimens of these phytoconstituents showed synergistic results in managing the physiological and biochemical features of depression. Thus, these neuroprotective could be utilized well in combination to manage depression-like symptoms during episodic stress. Furthermore, such results could be well justified when administered in polyherbal formulation with these neuroprotective as major components. In addition, an advanced study can be designed at the molecular and epigenetics level using a formulation based on these neuroprotective.