Mulberry Leaf Extracts and Neochlorogenic Acid Ameliorated Scopolamine-induced Cognitive Dysfunction through Promotion of Adult Hippocampal Neurogenesis

Abstract

Loss of neurogenesis leads to cognitive impairment and is one of the main causes of neuron degeneration diseases. Mulberry, an economic plant used as Chinese traditional herb, exhibits multiple biological properties. This study investigated the protective molecular mechanisms of mulberry leaf extracts (MLWE) and neochlorogenic acid (nCGA) on scopolamine-induced neuron cell death and cognitive dysfunction. Administration of MLWE and nCGA significantly improved cognitive functions in the Y-maze test of scopolamine-treated mice. MLWE and nCGA reversed scopolamine-reduced brain-derived neurotrophic factor (BDNF) expression and its downstream pathways. Immunohistochemical staining or Western blot analysis showed that MLWE and nCGA increased the expression of neurogenetic proteins such as nestin, NeuN, and doublecortin (DCX) in scopolamine-treated mice. They also reversed the hippocampus structure and neuronal proliferation, decreased Bax expression, and increased Bcl2 expression, thereby attenuating scopolamine-induced neural apoptosis. MLWE (0.5 mg m/L) and nCGA (10 μM) rescued scopolamine-induced cell death in SH-SY5Y cells. MLWE and nCGA repressed scopolamine-induced apoptosis, as evidenced by decreasing sub-G1 phase population through regulation of Bcl2 and Bax expression. Moreover, MLWE and nCGA promoted neurogenesis marker expression in SH-SY5Y cells. Our findings revealed that MLWE and nCGA significantly reversed scopolamine-induced neuron damage through enhanced adult hippocampus neurogenesis.