Figure 3

Some triterpenoids exhibit their anti-inflammatory activity by inhibiting LPS-stimulated COX-2 and iNOS expression in macrophages by limiting the translocation of NF-κB protein into the nucleus. Signal-induced activation of IκB kinase leads to the phosphorylation and degradation of IκB, liberating NF-κB from the IκB inhibitory proteins. With the degradation of IκB, the NF-κB complex is then freed to enter the nucleus where it can ‘turn on’ the expression of specific genes that have DNA-binding sites for NF-κB nearby and induces the expression of iNOS and the release of proinflammatory such as MIF, IL-6, IL-1, TNF-α. TNF-α is triggering either pro-inflammatory effects via NF-κB related pathways or apoptosis through activation of caspase-8 and triterpenoids induce apoptosis by modulating different caspases and their cleavage. TNF binds its receptor TNF-α and can activate the pro-inflammatory and anti-apoptotic NF-κB pathway via activation of the IKK complex. Moreover, TNF can induce the pro-apoptotic caspase–cascade via adaptor proteins TRADD and FADD and proteolytic activation of procaspase-8. Activated caspase-8 in turn cleaves and thus activates effector caspases such as caspase-3 and induces the apoptosis eventually.