Neuroprotective Role of Synthetic Peptide DP1 in Reducing Inflammation‐Associated Brain Damage and Cognitive Impairments

Neuroinflammation serves as a central process in the development of various neurodegenerative diseases, often triggered by systemic inflammation. Within the realm of current scientific investigation, there is considerable interest in antimicrobial peptides (AMPs) due to their versatile attributes, extending beyond their traditional antimicrobial functions, encompassing significant anti-inflammatory properties. Among these, the novel peptide DP1 stands out as an example, exhibiting antimicrobial and anti-inflammatory properties. This study evaluates the anti-inflammatory potential of DP1 against lipopolysaccharide (LPS)-induced neuroinflammation in rats. Neuroinflammation was induced via intraperitoneal (ip) injection of LPS (1 mg/kg body weight), followed by DP1 treatment (1.25 mg/kg body weight) in adult male Sprague Dawley rats. The alteration in the brain was monitored by biochemical, behavioral, histopathological, and immunohistochemical analysis. LPS-induced cognitive deficits were significantly improved by DP1 administration. Biochemical alterations and neuroinflammatory markers, including microglial and astrocytic activation, were restored to normal levels following DP1 treatment. Histopathological analysis confirmed reduced neurodegeneration. In conclusion, our results showed that DP1 inhibited LPS-induced microglial and astrocytic activation, restored the extent of neurodegeneration in different regions of the rat brain, thereby mitigating neuroinflammation as well as neuroinflammation-induced learning and memory deficits in rats.