Synergistic Effect of Compounds from a Chinese Herb: Compatibility and Dose Optimization of Compounds from N-Butanol Extract of Ipomoea stolonifera

The herbal medicine Ipomoea stolonifera (I. stolonifera) has previously been shown to have considerable anti-inflammatory potential in vivo and in vitro. To establish a method for exploring the synergistic effects of multiple compounds, we study the compatibility and dose optimization of compounds isolated from n-butanol extract of I. stolonifera (BE-IS). Raw264.7 cell was treated with lipopolysaccharide (LPS) in the presence of compounds from BE-IS, namely scopoletin, umbelliferone, esculetin, hesperetin and curcumin, using the orthogonal design, uniform design and median-effect method. To verify the best efficacy of principal constituents in vivo, the uniform design was used in the croton oil-induced mouse ear edema model. The results from LPS-induced the production of prostaglandin E-2 (PGE(2)) show that, esculetin, curcumin and hesperetin were the principal constituents that had synergistic effects when used at the optimal ratio. Additionally, the principal constituents were found to work synergistically in the croton oil-induced mouse ear edema model at low doses. It turned out that the three experimental optimization and analysis methods (orthogonal design, uniform design and median-effect method) can be effectively used to solve both compatibility and dose optimization for combined use of multiple compounds.