Immune-Enhancing Effects of Co-treatment With Kalopanax pictus Nakai Bark and Nelumbo nucifera Gaertner Leaf Extract in a Cyclophosphamide-Induced Immunosuppressed Rat Model

Abstract

ObjectiveImmune system disorders can result in various pathological conditions, such as infections and cancer. Identifying therapies that enhance the immune response might be crucial for immunocompromised individuals. Therefore, we assessed the immune-enhancing effect of co-treatment with Kalopanax pictus Nakai Bark and Nelumbo nucifera Gaertner leaf extract (KPNN) in a cyclophosphamide (Cy)-induced immunosuppressed rat model.Materials and MethodsFor in vitro studies, macrophages and splenocytes were treated with various KPNN doses in the presence or absence of Cy. Macrophage viability, nitric oxide production, splenocyte viability, cytokine production and natural killer (NK) cell activity were analyzed. For in vivo studies, analysis of weekly body weight, dietary intake, tissue weight, immune-related blood cell count, cytokine levels, and spleen biopsy was performed in a Cy-induced immunocompromised animal model.ResultsKPNN significantly increased phospho-NF-κB and phospho-ERK protein levels and cell viability in macrophages. KPNN significantly increased the NK cell activity in splenocytes compared to that in the control. Cy treatment decreased tumor necrosis factor (TNF)-α, interleukin (IL)-6, and interferon-γ production. In the Cy-induced immunosuppression rat model, KPNN-treated rats had significantly higher body weights and tissue weights than the Cy-treated rats. Additionally, KPNN treatment restored the immune-related factors, such as total leukocyte, lymphocyte, and intermediate cell contents, to their normal levels in the blood. The blood cytokines (TNF-α and IL-6) were increased, and spleen tissue damage was significantly alleviated.ConclusionsCollectively, KPNN exerts an immune-enhancing effect suggesting their potential as an immunostimulatory agent or functional food.

Euonymus alatus (Thunb.) Siebold leaf extract enhanced immunostimulatory effects in a cyclophosphamide-induced immunosuppressed rat model

“…Inflammatory M1 macrophages are also found in chronically inflamed tissues and have been shown to activate other immune cells such as monocytes, neutrophils, and T cells (43). In previous studies, the contents of total leukocytes, lymphocytes, granulocytes, and mid-size cells (Mid) were significantly decreased in the Cy-treated group compared with those in the normal group (12,15,17,40). As in the previous study, our results showed that the decreased number of immune cells in Cy-induced immunosuppressed rats significantly increased the number of total leukocytes, lymphocytes, granulocytes, and Mid after administration of EA extract.…”

“…MAPK and NF-κB signaling play critical roles in the immune response (28)(29)(30)(31)(32). A previous study reported that several natural products could show immune enhancement by activating the phosphorylation of inducible Nitric Oxide Synthase (iNOS), cyclooxygenase-2 (COX-2), NF-κB, and MAPKs (JNK, ERK, and p38) in RAW-264.7 cells (17,(33)(34)(35). Our results showed that p-ERK and p-NF-κB protein levels in the EA-treated group were higher than in the control group.…”

“…This innate immune response activates other inflammatory cells to enhance the adaptive immune response (44). As essential regulatory cells of the adaptive immune system, T cells promote the secretion of IL-2, TNF-α, and IFN-γ from Th1 cells and IL-4, IL-6, and IL-10 from Th2 cells (15)(16)(17)30). TNF-α produced by lymphocytes and macrophages protects the host from infectious pathogens (45).…”

“…Recognition of LPS by Toll-like receptor 4 in macrophages is known to increase the production of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, through activation of the NF-κB signaling pathway (48). Previous studies have reported that Cy-induced immunosuppression in vitro and in vivo significantly reduces the levels of cytokines, such as TNF-α, IFN-γ, IL-2, IL-6, and IL-10 (12,(15)(16)(17). Our results confirmed that the decreased levels of TNF-α and IFN-γ in Cy-induced immunosuppressed rats significantly increased when EA was administered.…”

“…Cy may cause drastic changes in the Th1/Th2 ratio bias, leading to immunosuppression. The immunological effect of Cy decreases lymphocyte proliferation, including the proliferation of T cells, and reduces the production of Th1 cytokines, such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, and IL-12, and Th2 cytokines, such as IL-4, IL-6, and IL-10 (12,(15)(16)(17).…”