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

Abstract

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.

The combination of Ephedrae herba and coixol from Coicis semen attenuate adiposity via glucocorticoid receptor regulation

“…On the other hand, several studies have reported the anti-obesity e cacy of CS. However, the reported mechanism was different from that of EH 24 .…”

“…We hypothesized that some compounds in CS may enhance the pharmacological effect of EH. Hence, we tested the effects of two compounds of CS, identi ed in a previous study, on EH-treated adipocytes 24 .…”

“…In our earlier study, the herbal pair of EH and CS was evaluated for their effect on obesity 24 . Five ratios of the EH and CS mixture (0:100, 25:70, 50:50, 75:25, and 100:0 [w/w]) were evaluated for their antiadipogenesis effects on 3T3-L1 preadipocytes.…”

“…Five ratios of the EH and CS mixture (0:100, 25:70, 50:50, 75:25, and 100:0 [w/w]) were evaluated for their antiadipogenesis effects on 3T3-L1 preadipocytes. The 50:50 EH-CS combination attenuated lipid accumulation and adipogenic gene expression signi cantly while increasing the phosphorylation of AMPactivated protein kinase (AMPK), with relatively low in ammatory pro les in palmitic acid-induced in amed preadipocytes 24 . However, the authors reported the limited e cacy of the CS extract alone on adipogenesis as compared to the signi cant effects of the mixed extract or the EH extract alone.…”

“…The key synergistic mechanism or principal molecule of EH-CS acting against adipogenesis remained unidenti ed. In particular, the key compound responsible for the improved e cacy of the herbal pair was not discussed and even the possibility of a pair of bioactive compounds was speculated from the network pharmacological analysis and other literature 24 .…”