Effects of Selected Resveratrol Analogues on Activation and Polarization of Lipopolysaccharide-Stimulated BV-2 Microglial Cells.

Increasing health-promoting effects of resveratrol and its molecular structural analogues have been discovered, and the acting mechanism has been explored. However, the activity comparison of such compounds in targeting macrophage-related inflammation associated with neurodegenerative diseases remains untouched. In this study, we evaluated the activation and polarization transition of lipopolysaccharide (LPS)-stimulated BV-2 mouse microglial macrophages exposed to resveratrol (RES) and its analogues pterostilbene (PTE), oxyresveratrol (ORES), acetyl-trans-resveratrol (ARES), and trans-2,3,5,4'-tetrahydroxystilbene-2-O-glucopyranoside (TSG). At 10 μM, all of the five stilbene compounds have effectively suppressed the LPS-stimulated BV-2 cell release of proinflammatory mediators 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 analogues 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 analogues.