Ziziphus jujuba “Huizao” Polysaccharides Exert Immunomodulatory Activity In Vitro and In Vivo by Modulating the TLR4/MAPK/NF-κB Signalling Pathway

<i>Ziziphus jujuba</i> is an important source of polysaccharides in food supply, and studies have demonstrated that polysaccharides serve as the principal active constituents responsible for immunomodulatory effects. The results indicated that "<i>Huizao</i>" polysaccharides (HP2-1) increased the viability and phagocytic activity of RAW264.7 cells and triggered immune responses by promoting cytokines TNF-α, IL-6, and IL-1β secretion, as well as NO and ROS production. In addition, HP2-1 also stimulated cytokine production, elevated immunoglobulin levels, and alleviated oxidative stress via increasing antioxidant enzyme activities and reducing MDA production in immunosuppressed mice. Furthermore, HP2-1 potentiated immune responses both in vitro and in vivo by modulating the TLR4/MAPK/NF-κB pathway due to upregulating TLR4 expression, leading to phosphorylation of ERK, JNK, and p38 MAPKs, thereby activating NF-κB and subsequent cytokine secretion.