Rhamnazin attenuates Amyloid β-Peptide (1–42) induced spatial memory impairments by modulation of BDNF-ERK signaling pathway

Abstract Rhamnazin (Rham), a natural flavonoid, possesses various medicinal benefits including anti-inflammatory, antioxidant, antiangiogenic, and antibacterial activities. Additionally, Rham showed neuroprotective effects when assessed using the chronic stress-induced cognitive impairment assay. In this intriguing investigation, researchers delved into the working memory and spatial reference memory of Rham, utilizing a rat model of Alzheimer’s disease (AD) induced by amyloid β1-42 (Aβ1-42). Administering Aβ1-42 directly into the ventricles led to notable cognitive impairments in behavioral assessments of rats with AD. However, chronic treatment of Rham (30, 60, and 120 mg/kg) once per day during five consecutive days improved the cognitive functions of AD-induced rats in a dose-dependent manner which was not observed following the acute Rham treatment. Concurrently, Rham administration also increased the levels of BDNF and phosphorylated ERK in the hippocampus. Moreover, the cognitive boost triggered by Rham was replicated through the overproduction of BDNF in the hippocampus. However, this effect was thwarted by either the bilateral delivery of lentiviruses expressing BDNF shRNA into the hippocampus or by a targeted injection of an ERK inhibitor. In conclusion, chronic treatment with Rham improves the cognitive deficits in AD-induced rats possibly via the upregulation of BDNF/ERK signaling pathway in hippocampus.