Figure 3.

Phlorotannins inhibit the NF-κB pathway of microglial activation and the pro-inflammatory signaling cascade. Phosphorylated p38 activates NF-κB, which in turn promotes transcription of pro-inflammatory signaling molecules. Neuroinflammation generates ROS, NO and Ca²⁺, induces oxidative damage, and promotes neuron death. Phlorotannins inhibit NF-κB activity and also directly scavenge ROS, thereby reducing microglial recruitment and neuroinflammation, ultimately increasing neuron viability. Red flat-ended arrows indicate direct inhibition; red downward arrows indicate downregulation; asterisks indicate changes observed in Aβ and phlorotannin-treated cells; underlined proteins indicate direct downstream targets of NF-κB. NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; TNF-α, tumor necrosis factor alpha; IL-6, interleukin 6; IL-1β, interleukin 1 beta; PGE₂, prostaglandin E2; COX-2, cyclooxygenase-2; iNOS, inducible nitric oxide synthase; NO, nitric acid; ROS, reactive oxygen species; Aβ, amyloid beta. Adapted from previous studies in Table 2.