Valsartan reduced acetylcholine esterase activity by 73% and amyloid beta levels by 53%, improving cognitive function in LPS-induced Alzheimer’s disease model in mice.
Does valsartan mitigate neuroinflammation and cognitive deficits in an LPS-induced mouse model of Alzheimer's disease?
Valsartan mitigates LPS-induced cognitive dysfunction and neuroinflammation in mice by modulating the renin-angiotensin and endocannabinoid systems, suggesting potential neuroprotective benefits.
Effect estimate: null (95% CI null)
p-value: p=<0.05
Abstract Neuroinflammation is a critical aspect implicated in cognitive dysfunctions and neurodegenerative ailments such as Alzheimer’s disease (AD). β-amyloid (Aβ) peptide deposits and alterations in behavior and memory are important contributors to neuro-inflammatory pathways. The renin-angiotensin system (RAS) and endocannabinoid system (ECS) play a vital role in the pathophysiology of AD. The aim of this study is to illuminate the ameliorative effect of the antihypertensive drug valsartan (VAL) against lipopolysaccharide (LPS)-induced AD and study the cross-talk between ECS and RAS. Thirty two male Swiss mice were randomly divided into 4 groups as follows: Normal control group; LPS group (250 µg/kg; ip); valsartan groups (20 and 40 mg/kg; po). All treatments continued daily with LPS for seven consecutive days. Neuroprotective effects exerted by VAL are emphasized by improving motor functions and enhancing animal performance via the activity cage and Y-maze behavioral tests respectively. VAL inhibited toll-like receptor 4 (TLR4), which in turn deactivated the tumor necrosis factor-α (TNF-α)/nuclear factor kappa-B (NF-κB) inflammatory pathway together with a reduction of angiotensin-1 receptor (AT1R1) levels as compared to LPS-injected animals. Additionally, VAL improved neuronal and cognitive dysfunction by reducing acetylcholine esterase activity (AChE) by 73% and amyloid beta (Aβ 1–42) by 53%, along with an elevation in the expression of cannabinoid 1 receptor (CB1R). Moreover, VAL enhanced the expression of protein kinase B (AKT) and heme oxygenase-1 (HO-1) gene levels and consequently restored the antioxidant cellular defense mechanism. VAL ultimately combats against microglial activation, mitigates cognitive dysfunction, and halts the neurodegenerative perturbations of LPS via inhibiting Aβ deposition, neuroinflammation, and RAS with stimulation of ECS. Graphical Abstract
Salama et al. (Thu,) conducted a other in Alzheimer’s Disease (n=32). Valsartan vs. LPS group was evaluated on Cognitive dysfunction as measured by AChE activity and Aβ1–42 levels (null, 95% CI null, p=<0.05). Valsartan reduced acetylcholine esterase activity by 73% and amyloid beta levels by 53%, improving cognitive function in LPS-induced Alzheimer’s disease model in mice.