Immunomodulatory Effects of Jujube (Ziziphus jujuba Mill.): A Review of Molecular Mechanisms and Cytokine Regulation

Ziziphus jujuba (Z. jujuba) Mill. (Rhamnaceae), commonly known as jujube, has been used in traditional medicine systems including Traditional Chinese Medicine, Ayurveda, and Un ani medicine for thousands of years. The fruit contains various bioactive compounds such as polysaccharides, triterpenoids, flavonoids, and saponins, which contribute to its diverse pharmacological activities. This review comprehensively summarizes the immunomodulatory effects of Z. jujuba and its bioactive constituents, with particular focus on molecular mechanisms and cytokine regulation. Z. jujuba exhibits bidirectional immunomodulatory properties: enhancing immune function in normal or immunosuppressed states while suppressing excessive inflammatory responses in pathological conditions. In macrophages, Z. jujuba extracts increase pro-inflammatory cytokine expression under normal conditions but inhibit lipopolysaccharide-induced inflammatory mediators. Polysaccharides from Z. jujuba promote splenocyte and lymphocyte proliferation and enhance spleen and thymus indices in vivo. The anti-inflammatory effects are mediated through suppression of NF-κB and MAPK pathways, accompanied by Nrf2/HO-1 pathway activation. Polysaccharides also modulate gut microbiota composition, influencing systemic immunity through the gut-immune axis. Z. jujuba regulates the expression of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 across various disease models affecting the gastrointestinal, hepatic, nervous, musculoskeletal, and respiratory systems. These findings suggest that Z. jujuba and its constituents represent promising candidates for the development of immunomodulatory agents with therapeutic potential in inflammatory and immune-related disorders.