Through pattern recognition receptors, infections and tissue injuries drive innate immune cells to trigger
inflammation with elevated cytokines, chemokines, growth factors, and other mediators. Inflammation resolves upon
removal of pathogenic signals and the presence of pro-resolving conditions including combating adaptive immunity.
Failure of resolution progresses into chronic inflammation, manifesting as detrimental disease development known as
inflammatory diseases including cardiovascular diseases, diabetes, obesity, cancers, etc. Inflammation typically involves
activations of many intracellular signaling pathways such as PI3K/AkT/mTORC1, PI3K/AkT/IKK(JNK),
Ras/Raf/MEK/ERK, JAK/STAT, etc.; these pathways could in turn mediate the upregulations of proinflammatory
transcription factors (e.g., NFκB, activator protein 1 (AP-1), HIF, signal transducer and activator of transcription (STAT),
etc.). Furthermore, the resulting FOXO inactivation ensures inflammatory proceeding. This review provides a systematic
view that polyphenols target multiple inflammatory components and reinforce anti-inflammatory mechanisms by
antioxidant potentials, AMPK activation, PI3K/AkT inhibition, IKK/JNK inhibition, mTORC1 inhibition, JAK/STAT
inhibition, TLR suppression, and ACE inhibition. As a result, polyphenols readily lead to NFκB, AP-1, HIF, and STAT
inactivations with reduced proinflammatory mediator generation. In conclusion, polyphenols sustain resolution of
inflammation and antagonize against proinflammation, which is readily consistent with diverse anti-inflammatory actions.
The promoted, restored, and maintained tissue homeostasis beyond its anti-inflammatory effects also extends to diverse
health benefits for disease preventions and interventions.