Medicinal Plant Research 2025, Vol.15, No.4, 178-187 http://hortherbpublisher.com/index.php/mpr 182 4.3 Cross-talk between inflammation and immunity ASPs help maintain the balance between immune tolerance and inflammatory response, through regulating the activity of myelogenic suppressor cells (MDSCs) and the Th1/Th2 cytokine profile (Wang et al., 2020b; Shen et al., 2022). Although ASPs usually show enhanced immune function, they can promote the proliferation and immunosuppressive function of MDSCs, by the STAT1/STAT3 signaling pathway. This effect helps control excessive inflammation, but if not regulated properly, it may also bring the risk of immunosuppression (Shen et al., 2022). ASPs also can regulate a wide range of cytokine networks, enhance the secretion of IL-2, IFN-γ, IL-6 and TNFα, while reducing the levels of IL-4 and, in some cases, IL-10 (Wang et al., 2020a). This comprehensive regulatory mechanism serves as the foundation for its immunomodulatory and anti-inflammatory effects, helping to enhance the body's resistance to infections, tumor growth, and immune-related diseases. ASPs can simultaneously regulate pro-inflammatory and anti-inflammatory factors, highlighting its potential as a balanced immunomodulator (Wang et al., 2016; Gu et al., 2019; Zhang et al., 2021). 5 Cellular and Molecular Evidence of A. sinensis Polysaccharides 5.1 In vitro cell studies ASPs have been widely studied in various in vitro inflammatory models, like LPS-induced macrophage models. The results show that, ASPs can enhance the phagocytic activity of macrophages, promote their proliferation, and regulate the release of inflammatory mediators, including IL-1β, IL-6 and TNF-α (Wang et al., 2016). Furthermore, in models induced by hydrogen peroxide or tert-butyl hydrogen peroxide, ASPs can protect chondrocytes from oxidative stress, and apoptosis damage by reducing ROS levels, and improving mitochondrial function (Zhuang et al., 2016; Ni et al., 2023). Commonly used molecular markers, like iNOS, COX-2 and various pro-inflammatory cytokines, can be detected by qRT-PCR and western blotting to evaluate the anti-inflammatory effect of ASPs. Studies have shown that, ASPs can up-regulate antioxidant enzymes (e.g., SOD2), down-regulate the expression of inflammatory mediators, and restore the levels of extracellular matrix proteins in chondrocytes (Zhuang et al., 2016; Ni et al., 2023). Flow cytometry and apoptosis experiments, further verified the protective and regulatory effects of ASPs in immune cells and non-immune cells. 5.2 Animal model research ASPs has been validated in a variety of animal models, including acute and chronic inflammation, osteoarthritis, liver fibrosis, and tumor models. In osteoarthritis models, administration of ASPs can improve cartilage degeneration, enhance mitochondrial metabolic function, and reduce chondrocyte apoptosis (Ni et al., 2023). In liver fibrosis and chemotherapy-induced injury models, ASPs reduce tissue damage, improve hematopoietic function, and promote immune cell recovery (Wang et al., 2020a; Du et al., 2023; Xiao et al., 2023; Sun et al., 2024). Serum cytokine detection showed that, ASPs could reduce pro-inflammatory factors (TNF-α, IL-1β, etc.) and increase the levels of anti-inflammatory or regulatory factors (e.g., IL-22, IFN-γ) (Wang et al., 2016; 2020a; Du et al., 2023). Histopathological analysis indicated that, the inflammatory infiltration of animal tissues treated with ASPs was reduced, the tissue structure was protected, and the burden of fibrosis or tumor was alleviated (Wang et al., 2020a; Zhao et al., 2021; Ni et al., 2023). 5.3 Molecular target verification Western blotting, is often used to verify the regulatory effects of ASPs on signaling pathways, like the PPARγ/SOD2/ROS pathway in chondrocytes, the IL-22/STAT3 pathway in the liver, and the PI3K/AKT pathway in the spleen and bone marrow (Wang et al., 2020a; Du et al., 2023; Ni et al., 2023). Immunofluorescence and immunohistochemical experiments, further confirmed the regulation of ASPs on the localization and expression levels of key proteins in tissues and cells (Ni et al., 2023).
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