Astragalus Extract Mixture HT042 Reverses Cyclophosphamide-Induced Immunosuppression Through Dual Modulation of Innate and Adaptive Immunity

Deficiencies in immune function increase susceptibility to infections and chronic diseases by impairing immune surveillance and tolerance mechanisms, especially in children with immature immune systems. Chronic inflammation associated with immune dysfunction can impair childhood by suppressing the GH-IGF-1. HT042 is composed of <i>Astragalus mongholicus</i>, <i>Eleutherococcus senticosus</i>, and <i>Phlomis umbrosa</i>, which are medicinal herbs that are traditionally utilized in East Asia to promote growth and enhance immune function; thus, HT042 itself holds potential as an immunomodulator. We evaluated the immunomodulatory effects of HT042 in a cyclophosphamide (CYP)-induced immunosuppressed mouse model, as well as in ex vivo primary splenocytes and RAW 264.7 macrophages. HT042 demonstrated remarkable immune-enhancing effects, including the restoration of weight loss and hematological parameters, as well as enhancing NK cell activity. Primary splenocytes treated with HT042 showed increased expression of CD3, CD4, and CD8, along with Th subset transcription factors (T-bet, GATA3, RORγt, Foxp3) and corresponding cytokines (IFN-γ, IL-4, IL-17, IL-10). In RAW 264.7 macrophages, HT042 increased nitric oxide production and upregulated NOS2, COX-2, and inflammatory cytokines (IL-6, IL-1β, TNF-α). It is noteworthy that HT042 enhances both innate and adaptive immune pathways, particularly via T cell modulation and macrophage activation, as this study is among the first to demonstrate such effects in the context of CYP-induced immunosuppression.