Antineuroinflammatory Effect of Amburana cearensis and Its Molecules Coumarin and Amburoside A by Inhibiting the MAPK Signaling Pathway in LPS-Activated BV-2 Microglial Cells

Figure 7

Proposed signaling mechanism for the effects of DEAC and chemical constituents (CM and AMB) in LPS-induced neuroinflammation in BV-2 cells. Activation of toll-like receptor 4 (TLR-4) with LPS leads to activation of the NF-κB and MAPK pathways. The IKK complex phosphorylates IkBα, which leads to the degradation of IkBα and subsequent nuclear translocation of NF-κB. At the same time, the MAPK pathway (JNK and ERK1/2) regulates the transcription of inflammatory mediators through the activation of the transcription factor AP-1. Activation of NF-κB and AP-1 results in the expression of iNOS and the production of proinflammatory mediators. DEAC disrupts LPS-induced neuroinflammatory pathways, decreasing JNK and ERK1/2 signaling. DEAC and chemical constituents decrease the expression of iNOS, as well as the production of inflammatory mediators (NO and cytokines). IKK: IκB kinase complex; IκBα: kappa B inhibitor; P: phosphate; NF-κB: nuclear kappa factor B; MAPK: mitogen-activated protein kinase; ERK: extracellular signal regulatory kinase; AP-1: activator protein 1.