Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

Cognitive decline is one of the most challenging issues for cancer survivors undergoing doxorubicin (DOX) based chemotherapy. Oxidative stress and inflammation primarily through tumor necrosis factor-alpha (TNF-α) are considered the key contributors to DOX-induced chemobrain. Berberine (BBR) has attracted much interest because of its anti-oxidative, anti-inflammatory and anti-apoptotic actions. This study aimed to evaluate the potential neuroprotective effect of BBR in DOX-induced neurodegeneration and cognitive deficits. Chemobrain was induced by DOX i.p. injection at the dose of 2 mg/kg, once/week, for four consecutive weeks. Rats were treated with BBR (100 mg/kg, p.o.) for 5 days/week for four consecutive weeks. BBR significantly attenuated behavioral defects in DOX-induced cognitive impairment. Besides, BBR reversed histopathological abnormalities. Mechanistically, it reversed DOX-induced neuroinflammation by attenuating NF-κB gene and protein expression in addition to diminishing expression of pro-inflammatory mediators (TNF-α and IL-1β), as well as apoptotic related factors (Bax, Bcl2 and Bax/Bcl2 ratio). Additionally, BBR activated the anti-oxidative defense via upregulating the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and manganese superoxide dismutase (MnSOD). BBR improved synaptic plasticity through cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF). These effects were related through the modulation of Sirtuin1 (SIRT1) expression. BBR is highlighted to induce neuroprotection against DOX-induced cognitive decline through modulating brain growth factors and imposing an anti-inflammatory, anti-apoptotic and anti-oxidative effects. Copyright © 2021. Published by Elsevier Inc.

Citation

Fatma H Shaker, Marwa O El-Derany, Sara A Wahdan, Ebtehal El-Demerdash, Hala O El-Mesallamy. Berberine ameliorates doxorubicin-induced cognitive impairment (chemobrain) in rats. Life sciences. 2021 Mar 15;269:119078

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 33460662

View Full Text