Anti-Mutagenic and Immunomodulatory Effects of Astragali Radix Extract on a Cyclophosphamide-Induced Immunosuppressed Mouse Model

Abstract

Although the immunomodulatory effects of Astragali Radix extract (AR) have been documented, its anti-mutagenic activity, a problem arising from chemotherapeutic agents, is rarely reported. Therefore, the anti-mutagenic and immunomodulatory effects of AR were investigated using a cyclophosphamide (CPA)-induced immunosuppressed mouse model to develop an alternative immunomodulatory agent. The fluid-bed-dried aqueous extract of AR containing 37.5% dextrin and exopolymers purified from Aureobasidium pullulans SM-2001 (EAP) were used in this study. The therapeutic potentials of AR at doses ranging from 100 mg/kg to 400 mg/kg was estimated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based cytotoxicity and splenocyte proliferation assay, body weight and lymphatic organ weight measurements, hematological measurements, serum and spleen cytokine level measurements, natural killer (NK) cell activity measurements, real-time RT-PCR expressions of splenic mRNA, a micronucleus test, histopathological observations, and immunohistochemical measurements. In CPA-treated mice, a clear immunosuppressive effect was observed for all tested parameters. However, the oral administration of AR (100, 200, and 400 mg/kg) showed dose-dependent and favorable inhibitory activities on CPA-induced immunosuppression and mutagenicity as compared to 200 mg/kg EAP. Furthermore, AR (100–400 mg/kg) up-regulated the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) which are related to NK-, T-, and B-cell activation, with no critical cytotoxicity. The results of this study clearly demonstrate that AR at an appropriate oral dose could act as a potential alternative agent with significant anti-mutagenicity and immunomodulatory properties.