Prodigiosin (PDG) is a bacterial metabolite with numerous
biological and
pharmaceutical properties. Exposure to
aluminium is considered a root etiological factor in the pathological progress of
Alzheimer's disease (AD). Here, in this investigation, we explored the neuroprotective potential of PDG against
aluminium chloride (AlCl3 )-mediated AD-like neurological alterations in rats. For this purpose, rats were gavaged either
AlCl3 (100 mg/kg), PDG (300 mg/kg), or both for 42 days. As a result of the analyzes performed on the hippocampal tissue, it was observed that
AlCl3 induced biochemical, molecular, and histopathological changes like those related to AD. PDG pre-treatment significantly decreased
acetylcholinesterase activity and restored the levels of
brain-derived neurotrophic factor, monoamines (
dopamine,
norepinephrine, and
serotonin), and transmembrane
protein (Na+ /K+ -
ATPase). Furthermore, PDG boosted the hippocampal
antioxidant capacity, as shown by the increased
superoxide dismutase,
catalase,
glutathione peroxidase,
glutathione reductase, and
glutathione contents. These findings were accompanied by decreases in
malondialdehyde and
nitric oxide levels. The
antioxidant effect may promote the upregulation of the expression of
antioxidant genes (Nrf2 and HO-1). Moreover, PDG exerted notable anti-inflammatory effects via the lessening of
interleukin-1 beta,
tumor necrosis factor-alpha,
cyclooxygenase-2,
nuclear factor kappa B, and decreases in the gene expression of
inducible nitric oxide synthase. In addition, noteworthy decreases in pro-apoptotic (Bax and
caspase-3) levels and increases in anti-apoptotic (Bcl-2)
biomarkers suggested an anti-apoptotic effect of PDG. In support, the hippocampal histological examination validated the aforementioned changes. To summarize, the promising neuromodulatory, antioxidative, anti-inflammatory, and anti-apoptotic activities of PDG establish it as a potent therapeutic option for AD.