Immunotherapy with Chinese medicinal herbs. II. Reversal of cyclophosphamide-induced immune suppression by administration of fractionated Astragalus membranaceus in vivo

A partially purified fraction (F3) with an estimated molecular weight of 20,000 to 25,000 derived from the traditional Chinese medicinal herb Astragalus membranaceus, was found to possess a potent immunorestorative activity in vitro. Its capacity to aborogate the local xenogeneic graft versus host reaction (XGVHR) following injection in vivo was further studied in a newly developed animal model designed for preclinical evaluation of various biological response modifiers. F3 was injected intravenously into cyclophosphamide-primed rats at varied concentrations and schedules prior to grafting of mononuclear cells from healthy normal donors. Maximal abrogation of the local XGVHR mounted by the mononuclear cells, was observed following injection of 5.55 mg of F3 daily for eight days. This abrogation of XGVHR indicates a reversal of the immunosuppressive effect of cyclophosphamide as manifested by a significant decline in the local XGVHR volume from 99.42 +/- 9.2 mm3 (positive control) to 39.78 +/- 8.3 mm3 (p less than 0.001). This reversal of cyclophosphamide-induced immunosuppression by the administration of F3 was complete, since the volume of the abrogated local XGVHR (39.78 +/- 8.3 mm3) was comparable to 34.79 +/- 5.69 mm3 (p greater than 0.1) in the negative control group (no cyclophosphamide-priming; saline injection only). These data indicate that F3 administration markedly enhances the rats' ability to reject the xenogeneic graft and therefore possesses a strong immune potentiating activity in vivo. These preclinical data also provide the rational basis for the use of extracts of Astragalus membranaceus in phase I clinical trials among patients suffering from iatrogenic or inherent immune deficiency states.