Abstract
Immune dysregulation is a risk factor for several diseases, including infectious diseases. Immunostimulatory agents have been used for the treatment of immune dysregulation, but deleterious adverse effects have been reported. The present study aims to establish the anti-oxidant and immunity-enhancing effects of Sambu-Tang (SBT), composed of Panax ginseng and Aconitum carmichaeli, and stigmasterol (Stig), an active compound of SBT. Immune-related factors were analyzed in RAW264.7 macrophage cells, mouse primary splenocytes, and the serum and spleen of cyclophosphamide-induced immunosuppressed mice. Results showed that the production levels of nitric oxide (NO) and expression levels of inducible NO synthase and heme oxygenase-1 were increased following SBT or Stig treatment in RAW264.7 cells. SBT or Stig increased the production levels of G-CSF, IFN-γ, IL-12, IL-2, IL-6, and TNF-α and induced the activation of NF-κB in RAW264.7 cells. SBT or Stig promoted splenic lymphocyte proliferation and increased splenic NK cell cytotoxic activity. In addition, SBT or Stig enhanced the levels of IFN-γ, IL-12, IL-2, IL-6, or TNF-α in the serum and spleen of the immunosuppressed mice. SBT or Stig increased the superoxide dismutase activity in the spleen. Collectively, SBT and Stig possess anti-oxidant and immunomodulatory activities, so they may be considered effective natural compounds for the treatment of various symptoms caused by immune dysregulation.
Highlights
The present study showed that SBT augmented the release levels of G-CSF, IFN-γ, IL-12, IL-2, IL-6, and TNF-α from macrophages, which is in concordance with studies indicating their potential as immunity-enhancing agents by increasing the levels of immunostimulatory cytokines from macrophages [29,74]
We speculate that SBT or Stig may have applications for Nature Killer (NK) cell-based immunotherapy
We showed that the body weight and serum TNF-α and IL-6 levels were reduced on the 7th day after CTX injection, indicating immunosuppression by CTX (Supplementary Figure S3)
Summary
The immune system plays a critical role in controlling infections, healing injuries, and restoring homeostasis [1]. The anti-oxidant defense systems are important for the normal function of the immune system [2]. Immune dysregulation is a risk factor for several diseases, including autoimmune disease and infectious disease [3,4]. Patients with immunodeficiency disorders usually have increased frequency, severity, or persistence of infections [5]. Immunostimulatory agents have generally been used for the treatment of immune dysregulation, as well as infections or cancers [6,7]. Anti-oxidants improved immune function and decreased mortality induced by infections, such as coronavirus disease [2,8]
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