Neuroprotective effects of carbenoxolone against amyloid-beta 1-42 oligomer-induced neuroinflammation and cognitive decline in rats

The aggregation of A? plays a major role in the progression of Alzheimer's disease (AD) and induces neuroinflammation, neurodegeneration and cognitive decline. Recent studies have shown that the soluble aggregates of A? are the major culprits in the development of these aberrations inside the brain. In this study, we investigated the neuroprotective potential of carbenoxolone (Cbx), which has been found to possess anti-inflammatory and nootropic properties. Male SD rats (250-300 g) were divided into the four groups (n = 8 per group): (1) sham control rats injected with vehicles, (2) A? 1?42 group rats injected i.c.v. with A? 42 oligomers (10 ?l/rat), (3) A? 1?42+Cbx group rats injected i.c.v. with A? 42 oligomers (10 ?l/rat) and i.p. with carbenoxolone disodium (20 mg/kg body weight) for six-weeks and (4) Cbx group rats injected i.p. with carbenoxolone disodium (20 mg/kg body weight) for sixweeks. Progressive learning and memory deficits were seen through a battery of behavioral tests and a significant increase in the expressions of GFAP and Iba-1 was observed which resulted in the release of pro-inflammatory cytokines post A? oligomer injection. The levels of BDNF, Bcl-2 and pCREB were decreased while Bax, caspase-3, caspase-9 and cytochrome c levels were induced. Also, neurotransmitter levels were altered and neuronal damage was observed through histopathological studies. After Cbx supplementation, the expressions of GFAP, IBA-1, pro-inflammatory cytokines, iNOS, nNOS and nitric oxide levels were normalized. The expression levels of pro-apoptotic markers were decreased and neurotrophin levels were restored. Also, neurotransmitter levels and neuronal profile were improved and progressive improvements in behavioural performance were observed. Our results demonstrated that Cbx might have prevented the A? induced neurodegeneration and cognitive decline by inhibiting the neuroinflammation and inducing BDNF/CREB signalling. These findings suggest that Cbx can be explored as a potential therapeutic agent against the progression of AD. The aggregation of A beta plays a major role in the progression of Alzheimer's disease (AD) and induces neuroinflammation, neurodegeneration and cognitive decline. Recent studies have shown that the soluble aggregates of A beta are the major culprits in the development of these aberrations inside the brain. In this study, we investigated the neuroprotective potential of carbenoxolone (Cbx), which has been found to possess anti-inflammatory and nootropic properties. Male SD rats (250-300 g) were divided into the four groups (n = 8 per group): (1) sham control rats injected with vehicles, (2) A beta 1-42 group rats injected i.c.v. with A beta 42 oligomers (10 & micro;l/rat), (3) A beta 1-42+Cbx group rats injected i.c.v. with A beta 42 oligomers (10 & micro;l/rat) and i.p. with carbenoxolone disodium (20 mg/kg body weight) for six-weeks and (4) Cbx group rats injected i.p. with carbenoxolone disodium (20 mg/kg body weight) for six weeks. Progressive learning and memory deficits were seen through a battery of behavioral tests and a significant increase in the expressions of GFAP and Iba-1 was observed which resulted in the release of pro-inflammatory cytokines post A beta oligomer injection. The levels of BDNF, Bcl-2 and pCREB were decreased while Bax, caspase-3, caspase-9 and cytochrome c levels were induced. Also, neurotransmitter levels were altered and neuronal damage was observed through histopathological studies. After Cbx supplementation, the expressions of GFAP, IBA-1, pro-inflammatory cytokines, iNOS, nNOS and nitric oxide levels were normalized. The expression levels of pro-apoptotic markers were decreased and neurotrophin levels were restored. Also, neurotransmitter levels and neuronal profile were improved and progressive improvements in behavioural performance were observed. Our results demonstrated that Cbx might have prevented the A beta induced neurodegeneration and cognitive decline by inhibiting the neuroinflammation and inducing BDNF/CREB signalling. These findings suggest that Cbx can be explored as a potential therapeutic agent against the progression of AD.