Evaluation of the anti-depressant potential of EGCG-loaded nanoparticles in unstressed and stressed mice

Abstract

Epigallocatechin-3-gallate (EGCG) is a key bio-active component of green tea and has demonstrated significant antidepressant activity in laboratory animals. Nano-particulate drug delivery offers great potential to overcome drawbacks associated with EGCG i.e. its low solubility and stability by transforming it into effective deliverable drugs. In the current study, nano-formulations of EGCG alone and with piperine were synthesized using antisolvent precipitation methodology followed by evaluation of their in vivo antidepressant effect in unstressed and stressed Swiss male albino mice. The mice were exposed to distinct stressors i.e. tail pinch, induction of immobilization, etc. throughout a span of three weeks. Zein, a protein nanocarrier, was nano-encapsulated with EGCG (25 mg) and EGCG + piperine (25 mg + 5 mg). For a continuous three weeks, the mice were administered EGCG-loaded nanosuspensions (25 mg kg⁻¹) and EGCG–piperine nanocomplexes (25 mg kg⁻¹). To determine the impact of various medication treatments on stressed and unstressed mice, the tail suspension test (TST) was employed as a behavioural paradigm. Mice exposed to various drug treatments were also evaluated for the effect on locomotor activity. The animals were euthanized followed by further estimation of plasma corticosterone, plasma nitrite, brain malondialdehyde, brain MAO-A, brain reduced glutathione, and brain catalase levels. The EGCG–piperine nanocomplex (25 mg kg⁻¹) and paroxetine HCl (10 mg kg⁻¹) per se significantly reduced immobility time in unstressed and stressed mice as compared to their respective control groups treated with a vehicle. However, in the case of locomotor activity, no significant effect was observed. EGCG loaded nanosuspension, EGCG–piperine nanocomplex and paroxetine HCl significantly decreased plasma nitrite, and brain MAO-A, brain malondialdehyde and brain catalase levels. However, these drug treatments significantly increased plasma corticosterone and brain reduced glutathione levels in unstressed and stressed mice as compared to their respective control groups treated with a vehicle. So, the intraperitoneal administration of nanoformulations synthesized using EGCG alone and along with piperine significantly improves the antidepressant-like behavior in mice.