Network pharmacology predicts combinational effect of novel herbal pair consist of Ephedrae herba and Coicis semen on adipogenesis in 3T3-L1 cells

BACKGROUND: Herbal combinations are regarded as basic strategy in oriental medicine with various purposes. Ephedrae herba (EH) and Coicis semen (CS) are two herbal medicines used to treat obesity in many herbal prescriptions, yet the effect and significance of this herbal pair have not been evaluated. PURPOSE: This study is to elucidate the effect of a novel herbal pair, EH-CS, on obesity and identify the key synergistic mechanism underlying it. METHODS: We investigated the network of herbs comprising the anti-obesity herbal prescriptions. Using the tools of network pharmacology, we investigated the compound-target interactions of EH and CS in combination to predict their effects in combination. Five EH-CS samples with different EH to CS ratios were prepared to investigate their efficacies in adipocytes. RESULTS: 1-mode network analysis of herbs in prescriptions based on literature review revealed the importance of EH-CS in anti-obesity prescriptions. The herbal combination comprised of equivalent weights (1:1) of EH and CS most potently reduced mature adipocyte adiposity, although several markers of adipogenesis and lipid synthesis were more suppressed by pure EH. PTGS2 (COX-2 gene) expression, a common target of EH and CS as deduced by compound-target network analysis, was affected by EH-CS extract treatments. However, EH at high concentration (25 μg/ml) notably increased PTGS2 expression without adversely affecting cell viability. However, EH-CS combination of the same concentration markedly decreased PTGS2 gene expression. CONCLUSION: These results show that the compounds in CS and EH act in concert to enhance the pharmacological effect of EH, but control unexpected effects of EH treatment.