Centella asiatica (Gotu kola) ethanol extract up-regulates hippocampal brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling in chronic electrical stress model in rats

Objective(s): Impairment of hippocampus function as a center for memory processing occurs due to stress. Centella asiatica L. (Gotu kola) is known to improve memory, intelligence, and neural protection although the precise mechanism is not well understood. This study aimed to investigate the effects of ethanol extracts of C. asiatica toward MAPK expression as down-stream signaling of brain-derived neurotrophic factor (BDNF). Materials and Methods: We performed a chronic electrical stress model on 20 male Sprague Dawley rats (2 months-old, 180–200 g). Rats were divided into four groups: normal control group (Control) which received distilled water, and three treatment groups receiving oral Gotu kola ethanol extracts in oral doses of 150 mg/kg BW (CeA150), 300 mg/kg BW (CeA300), and 600 mg/kg BW (CeA600) over four weeks. Memory acquisition was assessed with Morris water maze. Hippocampus was harvested, then extracted for protein and RNA analysis. MAPK proteins (p38, ERK1/2, JNK) were measured using Western blot, meanwhile, BDNF and TrkB receptor were analyzed with real-time PCR (RT-PCR). Results: CeA600 group revealed improvement of memory performance as shown by reduction in time and distance parameters compared to control during escape latency test. This finding associated with significant elevation of hippocampal BDNF protein and mRNA level with up-regulation of TrkB mRNA expression in CeA600 group compared to control. Western-blot analysis showed significant up-regulation of ERK1/2 protein level in CeA600 group (P<0.05) compare to control. Conclusion: BDNF signaling through TrkB and ERK1/2 pathway contributes significantly to amelioration of memory performance after C. asiatica treatment in electrical stress model.

Keywords:

BDNF signaling , Chronic electrical stress model , Centella asiatica , ERK1/2 , TrkB