International Journal of Molecular Medical Science, 2024, Vol.14, No.6, 342-354 http://medscipublisher.com/index.php/ijmms 348 leading to improved immune responses. These cells are critical in adaptive immunity, where CD4+ T-cells assist in activating other immune cells, and CD8+ CTLs directly target and destroy infected or cancerous cells. The administration of LBPs has been shown to enhance the proliferation of both CD4+ and CD8+ cells, suggesting that they contribute to the re-establishment of immune homeostasis in conditions of immune suppression (Feng et al., 2020, Wang et al., 2021). In addition to restoring T-cell populations, LBPs also influence cytokine production, which plays a pivotal role in regulating immune responses. Specifically, LBP treatment has been found to increase the secretion of critical immune-related cytokines such as interleukin-2 (IL-2), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). IL-2 is essential for T-cell proliferation and differentiation, while IFN-γ activates macrophages and enhances antigen presentation, thus promoting a stronger immune defense. Furthermore, the increased production of IFN-γ indicates that LBPs promote a Th1-dominant immune response, which is crucial for defending against intracellular pathogens and cancer cells. This shift towards a Th1 response suggests that LBPs could be beneficial in enhancing immune responses in conditions such as cancer or infections where robust cellular immunity is required. Taken together, the modulation of T-cell responses and cytokine production by LBPs highlights their potential as immunotherapeutic agents, capable of both restoring immune function in immunocompromised individuals and enhancing immune responses in a range of diseases (Ding et al., 2019), (Feng et al., 2020). 4.3 Gut Microbiota interaction and immunity The gut microbiota plays a crucial role in regulating immune responses, and Lycium barbarum polysaccharides (LBPs) have been shown to significantly impact this interaction (Figure 3). LBPs act as prebiotics, modulating the composition of the gut microbiota by enhancing the growth of beneficial bacteria such as Lactobacillus, Bifidobacterium, and Akkermansia. These beneficial microbes are known to produce short-chain fatty acids (SCFAs) like butyrate, propionate, and acetate, which are critical for maintaining gut health and immune system balance. Studies on LBP-treated mice revealed that these polysaccharides could promote the production of SCFAs, which not only support intestinal integrity but also modulate immune functions by promoting anti-inflammatory pathways and enhancing the barrier function of the gut epithelium (Ding et al., 2019). The SCFAs produced by the gut microbiota help regulate the immune system by interacting with immune cells and modulating cytokine production, thereby creating an environment conducive to reducing inflammation and boosting immune responses. Furthermore, LBPs improve gut barrier function by promoting the expression of tight junction proteins such as ZO-1 and occludin, which are essential for maintaining intestinal permeability. A healthy gut barrier prevents the translocation of harmful pathogens and toxins into the bloodstream, thereby reducing systemic inflammation and protecting immune homeostasis. In immunosuppressed models, LBPs have been shown to restore the balance of gut microbiota and improve immune responses. For example, in cyclophosphamide-treated mice, LBP administration increased the diversity of beneficial bacteria and reversed gut dysbiosis caused by the chemotherapy drug, which led to enhanced immune function. The positive effects of LBPs on gut microbiota were closely associated with an increase in beneficial bacterial families such as Prevotellaceae and Ruminococcaceae, known for their roles in anti-inflammatory responses and SCFA production (Wang et al., 2021). This interaction between LBPs and the gut microbiota highlights their potential for therapeutic use in modulating immune responses and improving overall health, especially in conditions involving gut dysbiosis and immune dysfunction. 5 Synergistic Effects with Other Treatments 5.1 Combination with Chemotherapy Lycium barbarum polysaccharides (LBPs) have shown potential in boosting the efficacy of chemotherapy while minimizing its side effects. Chemotherapy is often accompanied by significant adverse effects, such as organ toxicity and reduced immune function. LBPs have demonstrated antioxidant and immune-enhancing properties, which can alleviate these side effects by reducing oxidative stress and inflammation. For instance, LBPs have been used in combination with chemotherapy drugs, such as 5-fluorouracil, to improve the tumor-killing effects in liver cancer models, while simultaneously reducing chemotherapy-induced toxicity (Han et al., 2022).
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