Synergistic combinations of five single drugs from Centella asiatica for neuronal differentiation

To identify alternatives of nerve growth factor, which could promote NF68 protein expression and contribute toward neuronal differentiation, five compounds namely: asiatic acid, madecassic, madecassoside, quercetin, and isoquercetin, obtained from Centella asiatica, were examined for their neuronal differentiation effects on PC12 cells. C. asiatica has been applied as an effective herbal medicine for the treatment of various diseases, including depression. According to a statistical design of experiments, both single compound and compound combinations were evaluated. A further statistical analysis indicated quantitative interactions between these five single compounds and led to the identification of the optimal drug combinations. Asiatic acid and madecassic appeared to show profound synergistic effects on neurofilaments expression in vitro. The optimized drug combinations were significantly more potent than single drugs and further investigation suggested that the optimal drug combination could be an analogue of nerve growth factor and could represent a potential treatment for neurodegenerative diseases.