International Journal of Molecular Medical Science, 2025, Vol.15, No.2, 89-97 http://medscipublisher.com/index.php/ijmms 91 Atomic force microscopy (AFM) and scanning electron microscopy (SEM) are used to observe the microscopic morphology of polysaccharides. AFM showed that some polysaccharides of Cordyceps sinensis formed large networks composed of three helical chains in aqueous solution (Wang et al., 2011). SEM provides intuitive images of the surface morphology and aggregation state of polysaccharides. 3 The immunomodulatory effect of Cordyceps polysaccharides 3.1 Regulation of innate immunity Cordyceps polysaccharides can significantly activate macrophages, enhance their phagocytic ability and promote the secretion of inflammatory factors such as TNF-α and IL-1β. For example, Cordyceps militaris polysaccharide SDQCP-1 can induce macrophages to release NO, TNF-α, IL-6 and IL-10, promoting M1 polarization (Zhang et al., 2020). Similarly, CMP-III from military pupae enhances the phagocytosis and cytokine production of macrophages by activating the MAPK and NF-κB pathways (He et al., 2019). Furthermore, studies have shown that CMPB90-1 may enhance phagocytosis and promote M1 polarization through the TLR2, MAPK and NF-κB pathways (Bi et al., 2018). Cordyceps polysaccharides can also enhance the vitality of NK cells, which is very important for resisting viruses and tumors. Experiments show that CMPB90-1 can enhance the lethality of NK cells, which play an important role in eliminating tumors and viruses in the innate immune system (Bi et al., 2018). In addition, Cordyceps spore polysaccharides can also improve the attacking ability of NK cells in mice with low immunity, showing the possibility of strengthening the innate immune system (Zheng et al., 2022). 3.2 Regulation of acquired immunity Polysaccharides from Cordyceps sinensis can promote the growth of T cells, regulate the Th1/Th2 immune balance, and play a key role in the acquired immune system of the human body. For example, silkworm pupa polysaccharide CP2-c2-s2 can significantly stimulate T cell proliferation, indicating that it can enhance the acquired immune response (Liu et al., 2016). Another study shows that CMPB90-1 can increase the number of specific T cells, further confirming its regulatory effect on acquired immunity (Bi et al., 2018). In addition to affecting T cells, this type of polysaccharide can also activate B cells and promote antibody production. Experiments have confirmed that CP2-c2-s2 can promote B cell proliferation, which is very important for antibody formation and humoral immune function (Liu et al., 2016). The increase in B cell activity indicates that this type of polysaccharide can help the body better resist bacteria. 3.3 Multiple mechanisms of action This type of polysaccharide regulates the immune system through multiple sites of action, mainly by binding to TLR receptors, thereby initiating different signaling channels. Studies have shown that Cordyceps militaris polysaccharides can activate important signaling channels such as TLR2 and MAPK, which are crucial for immune responses. For example, CMPB90-1 can accelerate the growth of splenic lymphocytes, enhance the lethality of NK cells, and increase the release of IL-2 factor simultaneously (Bi et al., 2018). Another experiment found that this type of polysaccharide can also activate macrophages through the MAPK channel and control the production of inflammatory factors (Liu et al., 2021). These results confirm that polysaccharides are a key pathway for regulating immunity by binding to TLR receptors and initiating related signaling channels (Figure 1) (He et al., 2019; Liu et al., 2024). Liu et al., 2024 pointed out that HCMP can activate the MAPK signaling pathway in RAW 264.7 cells. After stimulation by HCMP, signal proteins such as ERK, JNK and p38 are phosphorylated, thereby regulating the transcription of downstream genes. Meanwhile, the pathway also balances the expressions of pro-inflammatory factors such as TNF-α and IL-6 and anti-inflammatory factors such as TGF-β1 and Arg-1, enhancing the immune response of macrophages. 3.4 The effect is affected by the dosage and time The immunomodulatory effect of Cordyceps sinensis polysaccharides is directly related to the dosage and duration
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