RESUMEN
Amelioration of oxidative stress via promoting the endogenous antioxidant system and enhancement of monoamines in brain were the important underlying antidepressant mechanism of protocatechuic acid (PCA). The aim of the present study is to explore the potential antidepressant mechanism(s) PCA in chronic unpredictable mild stress (CUMS) mice. Mice were subjected to CUMS protocol for 4 weeks, and administered with PCA (100 and 200 mg/kg) and fluoxetine (20 mg/kg) for 24 days (from day 8th to 31st). Behavioral (sucrose preference, immobility time, exploratory behavior), and biochemical alterations such as serum corticosterone, brain derived neurotrophic factor (BDNF), inflammatory cytokines, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), and antioxidants parameters were investigated. Experimental findings revealed that CUMS subjected mice exhibited significant impairment in behavioral alterations, such as increased immobility time, impaired preference to the sucrose solution, BDNF levels and, serum corticosterone, cytokines, malondialdehyde (MDA) formation with impaired antioxidants in the hippocampus and cerebral cortex. Administration of PCA to CUMS mice attenuated the immobility time, serum corticosterone, cytokines TNF-α, and IL-6, MDA formation and improved sucrose preference, including restoration of BDNF level. Thus, the present findings demonstrated the antidepressant potential of PCA which is largely achieved probably through maintaining BDNF level, and by modulation of the oxidative stress response, cytokines systems, and antioxidant defense system in mice.
Asunto(s)
Antidepresivos/farmacología , Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Hidroxibenzoatos/farmacología , Estrés Oxidativo/efectos de los fármacos , Estrés Psicológico/tratamiento farmacológico , Animales , Biomarcadores/sangre , Encéfalo/metabolismo , Encéfalo/fisiopatología , Factor Neurotrófico Derivado del Encéfalo/sangre , Enfermedad Crónica , Modelos Animales de Enfermedad , Conducta Exploratoria/efectos de los fármacos , Preferencias Alimentarias/efectos de los fármacos , Interleucina-6/sangre , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Estrés Psicológico/sangre , Estrés Psicológico/fisiopatología , Estrés Psicológico/psicología , Factor de Necrosis Tumoral alfa/sangreRESUMEN
The motive of work was to develop a multi-walled carbon nanoplatform through facile method for transportation of potential anticancer drug doxorubicin (DOX). Folic acid (FA)-ethylene diamine (EDA) anchored and acid functionalised MWCNTs were covalently grafted with DOX via π-π stacking interaction. The resultant composite was corroborated by 1H NMR, FTIR, XRD, EDX, SEM, and DSC study. The drug entrapment efficiency of FA-conjugated MWCNT was found high and stability study revealed its suitability in biological system. FA-EDA-MWCNTs-DOX conjugate demonstrated a significant in vitro anticancer activity on human breast cancer MCF-7 cells. MTT study revealed the lesser cytotoxicity of folate-conjugated MWCNTs. The obtained results demonstrated the targeting specificity of FA-conjugate via overexpressed folate receptor deemed greater scientific value to overcome multidrug protection during cancer therapy. The proposed strategy is a gentle contribution towards development of biocompatible targeted drug delivery and offers potential to address the current challenges in cancer therapy.