Medicinal Plant Research 2025, Vol.15, No.4, 178-187 http://hortherbpublisher.com/index.php/mpr 180 3 Regulation of Inflammatory Signaling Pathways by A. sinensis Polysaccharides 3.1 Modulation of the NF-κB pathway Studies have shown that, A. sinensis polysaccharides (ASPs) can block the activation of the NF-κB pathway, by inhibiting the degradation of IκBα, thereby reducing the nuclear translocation of the NF-κB p65 subunit. This effect reduces the transcriptional activity of NF-κB, and subsequently inhibits the inflammatory response in various cell and animal models (Zhou et al., 2019; Tian et al., 2021; Zou et al., 2023). In LPS-induced and ischemia-reperfusion injury models, ASPs treatment can reduce the phosphorylation levels of IκBα and p65, which are key steps in NF-κB activation (Tian et al., 2021; Ye et al., 2023). By inhibiting NF-κB activation, ASPs can down-regulate the expression of various inflammatory mediators, like TNF-α, IL-1β, IL-6, iNOS, and chemokines (e.g., CCL2, CXCL8) (Tian et al., 2021; Ye et al., 2023; Zou et al., 2023). This mechanism is manifested as a reduction in pro-inflammatory cytokines, and relief of tissue inflammation in models such as colitis, arthritis and myocardial injury (Zhou et al., 2019). 3.2 Mechanisms of MAPK pathway regulation ASPs regulate the MAPK pathway, through inhibiting the phosphorylation of key kinases, like p38, ERK and JNK. This negative regulation reduces the activation level of MAPK-dependent transcription factors, thereby reducing the expression of inflammation-related genes (Xue et al., 2023). In fibroblast-like synovial cells and primary skin cells, ASPs inhibit MAPK signaling, exerting anti-inflammatory effects (Tian et al., 2021). Through the inhibition of the MAPK pathway, ASPs reduced the transcription of inflammation-related genes, and further restricted the production of cytokines and chemokines in the inflammatory response (Tian et al., 2021; Xue et al., 2023). This mechanism has been demonstrated in both in vivo and in vitro experiments, manifested as a reduction in tissue damage and inflammatory cell infiltration. 3.3 Other relevant pathways ASPs also exert anti-inflammatory effects, by inhibiting the JAK/STAT pathway, especially the JAK2/STAT3 signaling pathway. This inhibition reduces the expression of pro-inflammatory cytokines and mediators, which has been verified in models of rheumatoid arthritis, liver fibrosis and adjuvant arthritis (Zhou et al., 2019; Li et al., 2020; Wang et al., 2020a; Xue et al., 2023). In some cases, JAK2/STAT3 can act as an upstream of MAPK, suggesting its synergistic regulatory effect (Xue et al., 2023). Besides, ASPs can activate the Nrf2/HO-1 pathway, enhancing the body's antioxidant defense, and promoting anti-inflammatory effects. This dual regulation helps alleviate oxidative stress and inflammation, protect tissues and promote recovery (Wang et al., 2016; Xiao et al., 2023). ASPs promotes the expression of antioxidant enzymes, and reduces oxidative damage by activating Nrf2/HO-1 (Xiao et al., 2023). 4 Immunomodulatory Effects of A. sinensis Polysaccharides 4.1 Regulation of innate immunity ASPs can stimulate innate immune responses, especially in enhancing the proliferation and phagocytic activity of macrophages, as well as the release of inflammatory mediators. In vitro and in vivo studies have shown that, ASPs promote macrophage proliferation, enhance their phagocytic function, and increase the production of cytokines such as IL-1β and IL-12p70, as well as the expression of inducible nitric oxide synthase (iNOS) and lysozyme (Shen et al., 2022). ASPs can also upregulate the levels of surface molecules, liek ICAM-1 and TLR4, further promoting the activation of macrophages and pathogen recognition. And ASPs can activate natural killer (NK) cells, and increase the ratio of monocytes/macrophages in peripheral blood and spleen, enhancing non-specific immunity (Liu et al., 2019; Shen et al., 2022). In aquatic animal models (such as white shrimp), ASPs can increase survival rate and enhance the activities of phenol oxidase, superoxide dismutase and glutathione peroxidase, indicating that its immunostimulative effect is conserved across species (Pan et al., 2018).
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