Effect of active fractions in Yaotongning Capsule on prostaglandin E2, interleukin-2, and nitrogen monoxide production and their interactions / 中草药

ABSTRACT

Objective: To evaluate the in vitro effects of different combinations of the active fractions in Yaotongning Capsule (YTNC) on anti-inflammation, immunity, and activating blood circulation, and the interactions among these active fractions. Methods: Six samples were prepared by adding flavonoids, saponins, volatile oils/aqueous extracts, and polysaccharides, which were extracted from the material medicines in YTNC, to the alkaloids of Strychnos nux-vomica (Ma Qian Zi) and Ephedra sinica (Ma Huang) in turn according to the formulating principle of YTNC, combination chemistry concept, and their importance in the formula. The effects of the six samples on the production of lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) in Ana-1 cells, concanavalin (ConA)- induced interleukin-2 (IL-2) in splenocyte, and nitrogen monoxide (NO) in human umbilical vein endothelial cells (HUVEC) were explored by detecting their half-maximal inhibitory concentration (IC50) or half-maximal effective concentration (EC50). An innovative method based on least square optimization was applied to calculate the additive IC50/EC50 value of each sample. The interactions of the active fractions in these samples were investigated by comparing the additive IC50/EC50 values with the corresponding experimental IC50/EC50 values. Results: All the six samples could inhibit the production of PGE2 and promote the secretion of IL-2 in the investigated concentration range. Only sample III consisting of the alkaloids, flavonoids, and saponins from YTNC had the EC50 value of promoting NO production. Moreover, the sample also displayed excellent activities in the three models of LPS-induced PGE2 production, ConA-induced IL-2 production, and NO production, which could reflect the capability of anti-inflammation, enhancing the body's immunity, and activating blood circulation, respectively. Different combination of the active fractions from YTNC produced the different interaction types in the three models. And the active fractions in sample III, i.e., the alkaloids, flavonoids, and saponins from YTNC, generated high synergistic effects in all the three models. Conclusion: All the six samples derived from the different combination of the active fractions from YTNC show the good activity of inhibiting PGE2 production and promoting IL-2 secretion. Therefore, the YTNC formula is reasonable and has good activity of anti-inflammation and immunity. However, the YTNC formula still could be improved by reducing the categories of its active fractions because the combination of the alkaloids, flavonoids, and saponins exerted better activities than the other samples and the three kinds of active fractions produced an excellent synergistic effect in all the three models. Synthetically evaluating various activities of YTNC in the present work may lead to develop new Chinese materia medica for rheumatic arthralgia treatment, which is more effective and easily controllable in quality.