LAUSR

IIncreasing health promoting effects of resveratrol and its molecular structural analogs have been discovered and acting mechanism explored. However, the activity comparison in targeting macrophage-related inflammation associated with neurodegenerative diseases remains untouched. In this study, we evaluated activation and polarization transition of LPS-stimulated BV-2 mouse microglial macrophages exposed to resveratrol (RES) and its analogs pterostilbene (PTE), oxyresveratrol (ORES), acetyl-trans-resveratrol (ARES), and trans-2,3,5,4'-tetrahydroxystilbene -2-O-glucopyranoside (TSG). At 10 µM,all the five stilbene compounds have effectively suppressed LPS-stimulated BV-2 cell release of pro-inflammatory media such as NO, TNF-α, iNOS, IL-1β and IL-6. Mechanism study elucidated that they exert anti-inflammatory effects through MAPKs (ERK1/2, JNK, and p38) and NF-κB signaling pathways. Further investigation in treating BV-2 cells with resveratrol and its analogs revealed the reversal of LPS-induced phenotype molecules from M1 (iNOS, IL-1β, IL-6 and CD86) to M2 (Arg1, CD163, and IL-10) subtypes, manifesting that these five stilbenes suppressed inflammation through modulating the polarized phenotypes of BV-2 microglia. Most importantly, PTE demonstrated the most potent inhibitory activity among these five stilbene compounds. Therefore, this study not only highlights microglia-induced inflammatory responses as a potential therapeutic target, but also suggests future insights in considering the options of nutraceutical development for resveratrol and its analogs.