Nanosized epiberberine-loaded chitosan-collagen nanocomposites: synthesis and evaluation of their cognitive and AChE inhibition enhancing potential in a scopolamine-induced amnesia rat model.

Epiberberine is one of the main constituents of Coptidis Rhizoma and has been found to be active against diseases such as hyperglycemia, hyperlipidemia, and Alzheimer's disease. However, like other alkaloids its use is limited by rapid absorption, rapid metabolism and low transport to the brain. Nanotechnology has become a method of choice for a better delivery of active principles to the brain. The current study involved the use of a nanotechnological approach for the synthesis of epiberberine-loaded chitosan-collagen nanocomposites using natural polymers chitosan and collagen. This study was aimed at increasing the efficacy of epiberberine for dementia by decreasing the release rate and enhancing the anti-oxidant and AChE inhibition properties of epiberberine. The synthesized nanocomposites were found to be of small size (25 ± 2 nm) with more or less spherical morphology and showed slow release rate. Oxidative stress and impaired levels of acetylcholinesterase (AChE) are associated with the pathophysiology of Alzheimer's disease. These nanocomposites showed in vitro and in vivo anti-oxidant and AChE inhibition activity. Further, behavioral, biochemical, ELISA and immunohistochemical parameters were also used to evaluate the efficacy of these nanocomposites in a scopolamine-induced amnesia rat model. The results showed that these nanocomposites can reduce cognitive decline and are more effective against scopolamine-induced amnesia than epiberberine and the standard drug donepezil. At a similar concentration of 1 mg kg⁻¹ body weight, the p-values of nanocomposites were smaller (approximately 10⁻⁴ to 10⁻²) in comparison to epiberberine and donepezil, indicating a significant effect against scopolamine-induced amnesia. [ABSTRACT FROM AUTHOR]