Astragaloside IV Prevents Memory Impairment in D-galactose-induced Aging Rats Via the AGEs/RAGE/NF-κB Axis

Background. We investigated the effects of astragaloside IV (AS-IV) on memory function in aging rats mimicked by D-galactose administration and explored the potential molecular mechanisms. Methods. Twenty-seven male rats were randomly divided into control group (N = 9), model group (N = 9), and AS-IV treated group (N = 9). Aging model was stimulated by D-galactose (400 mg/kg/d, i.p., dissolved in saline) for 8 weeks in rats. The general status of the rats was observed weekly. Learning and memory function was determined using the eight-arm radical maze and step-down test. Pathological changes in the hippocampal CA1 region were determined by hematoxylin and eosin staining. Organ indexes, superoxide dismutase (SOD) activity and malonaldehyde (MDA) content in the serum were measured. Expression of advanced glycation end products (AGEs), receptor for AGEs (RAGE), nuclear factor-kappa B (NF-kappa B), interleukin (IL)-6, IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) were detected by enzyme-linked immunosorbent assay, real-time polymerase chain reaction or western blotting. Results. AS-IV improved the general status of the aging rats induced by D-galactose, prevented the impairment of memory function, organ indexes, and the pathological damage of the hippocampus. From the prospective of oxidative stress, AS-IV increased sera SOD activity and decreased MDA content. Additionally, AS-IV also reduced the inflammatory response by reducing hippocampal IL-1 beta, TNF-alpha, and IL-6 expression. Importantly, AS-IV prevented D-galactose-induced expression of AGEs, RAGE and NF-kappa B in the hippocampus. Conclusion. AS-IV could prevent D-galactose-induced aging and memory impairment in rats, likely via regulation of inflammatory response, which was modulated by AGEs/RAGE/NF-kappa B axis. (c) 2021 The Authors. Published by Elsevier Inc. on behalf of Instituto Mexicano del Seguro Social (IMSS). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

This study investigated the effects of astragaloside IV (AS-IV) on memory function in aging rats. The results showed that AS-IV improved memory function by regulating inflammatory response, reducing oxidative stress, and modulating advanced glycation end products.