Background Water extract (WAE) and ultrafine powder (UFP) are two types of commonly used supplements in preparing various pharmaceutical products and functional foods. However, the correlations of the chemical compositions with the traditional functions between WAE and the herb itself, as well as the potential problems of safety for UFP have been more and more concerned by many doctors and customers. Methods In this study, a new whole ingredients extract of Astragalus (WIE) was prepared using the gradient solvent extraction method. The chemical compositions of WIE and WAE were comparatively analysed using spectrophotometric and chromatographic approaches. In addition, the in vivo immunomodulatory effect of WIE, WAE and UFP of Astragalus were comprehensively compared in cyclophosphamide (Cy)-induced immunosuppressive mice. Results The compositions and contents of main active ingredients (polysaccharides, saponins and flavonoids) in WIE were determined to be more abundant than those in WAE. In Cy-induced immunosuppressive mice, oral administered with low dosage of WIE (equalled to 1.0 g herb/kg/day) for 18 consecutive days significantly improved the immune-related responses (body weight, number of peripheral white blood cells, thymus and spleen indexes, splenocyte proliferations, natural killer cell activity, splenic lymphocyte subset, and serum levels of immunoglobulins G and M). The potency of three Astragalus preparations on immunomodulation was observed to be WIE ≥ UFP > WAE. Conclusions WIE maximally retained the chemical integrity of astragalus, and presented better therapeutic effectiveness than UFP and WAE. It can be further developed as new strategy for reasonable use of medicinal/edible herb-derived supplement (extract) for pharmaceutical and healthcare applications. Electronic supplementary material The online version of this article (10.1186/s13020-019-0234-0) contains supplementary material, which is available to authorized users.

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