Figure 1.

Signal transduction pathway related to the immune-regulation of botanical polysaccharides in macrophage activation. Botanical polysaccharides can activate macrophages via different kinks of receptors, such as Toll-like receptor 4 (TLR4), Toll-like receptor 2 (TLR2), complement receptor 3 (CR3), mannose receptor (MR), scavenger receptor (SR), and Dectin-1. These receptors can work separately, and some different receptor types can cooperate with each other forming clusters of signaling complexes. (e.g., TLR4-CD14, TLR2-CD14, etc.) TLR4 and TLR2 ligation leads to the activation of IL-1R associated kinase (IRAK) via an adaptor myeloid differentiation protein 88 (MyD88), with subsequent activation of TNF receptor-associated factor 6 (TRAF-6), MAP kinases (e.g., p38 and JNK) and NF-κB. It can also activating phosphoinositide-3-kinase (PI3K)-Akt pathway via reactive oxygen species (ROS), then leading to activation of the mitogen-activated protein kinase (MAPK). SR- and CR3-activated signaling pathways lead to phospholipase C (PLC) activating, whose products activate protein kinase C (PKC) and PI3K, leading to activation of the MAPK, extracellular signal regulated kinase (ERK). Activated PKC can made IKK to be phosphorylated, IKK complex phosphorylates I-κB which leading the I-κB uniquitylated and degradated. In the end, nuclear factor-κB (NF-κB) liberated. Ultimately, these activating factors enter the nucleus cause induction of gene transcription. Activation of these transcription pathways induce expression of pro-inflammatory cytokines (TNF-α, IL-6, etc.) and inducible nitric oxide synthase (iNOS).