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

Abstract

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.

Pinosylvin Shifts Macrophage Polarization to Support Resolution of Inflammation

“…Interestingly, the effects of pinosylvin were shared by these two compounds, suggesting a group effect of pinosylvin-like stilbenoids. To support this finding, Wang et al recently reported that resveratrol, and its analogues (other than pinosylvin or monomethyl pinosylvin), enhanced the production of M2-markers (Arg-1, IL-10, and CD163), while inhibiting the production of M1-markers (NO, iNOS, IL-1β, IL-6, and TNFα) in BV-2 mouse microglial macrophages [ 12 ]. We were also interested if the effects found in murine macrophages would also be present in human cells.…”

Pterostilbene Attenuates Cocultured BV-2 Microglial Inflammation-Mediated SH-SY5Y Neuronal Oxidative Injury via SIRT-1 Signalling

“…Recently, accumulating evidences have demonstrated the benefits of PTE and other analogue stilbenoids, including resveratrol, piceatannol, and gnetol, against inflammatory and oxidative processes in vitro and in vivo [ 9 ]. The anti-inflammatory effects of PTE involve many intra- and extracellular signals, including nitric oxide (NO), inducible nitric oxide synthase (iNOS), NLRP3, NF- κ B, TNF- α , and ILs [ 26 – 28 , 42 , 43 ]. We previously reported that PTE alleviates early inflammatory injury after SAH by inhibiting NLRP3 inflammasome and Nox2-related oxidative stress [ 24 ] and also attenuates the secondary astrocyte-induced inflammatory and oxidative stress after ischemia reperfusion injury by suppressing NF- κ B signalling [ 18 ].…”

“…A recent study compared the protective effects of PTE and its structural analogues on neurodegenerative diseases. It evaluates activities of these analogues on the LPS-induced release of proinflammatory factors, containing NO, iNOS, IL-6, IL-1 β , and TNF- α , in BV-2 cells, and further involvement of the MAPKs (ERK1/2, JNK, and p38) and NF- κ B signalling pathways [ 28 ]. Also, PTE was proved to attenuate the neuroinflammatory response induced by amyloid- β in BV-2 microglia through inhibiting the NLRP3/caspase-1 inflammasome pathway [ 26 ], indicating a therapeutic effect of PTE in AD.…”

“…Previously, we have found that PTE attenuates neural impairments in different neurological disorders, including glutamate or high-glucose-induced oxidative stress in neural cells [ 19 , 20 ], inflammation and mitochondrial oxidative stress injury after cerebral ischemia reperfusion [ 18 , 25 ], inflammation and oxidation-involved early brain injury following subarachnoid haemorrhage (SAH) [ 24 ]. Additionally, recent studies have shown that PTE inhibits the amyloid- β - and lipopolysaccharide- (LPS-) induced activation of microglia [ 26 – 28 ], whereas, it remains not fully clear whether PTE exerts neuronal protective effects by regulating microglia-mediated inflammatory and oxidative injury, as well as the molecular mechanisms.…”

In vitro antioxidant and antitumor study of zein/SHA nanoparticles loaded with resveratrol

“…Resveratrol (RES) is a natural polyphenol molecule with anti‐inflammatory (Gambini et al., 2015; Pujara et al., 2021; Vella et al., 2015; Wahab et al., 2017), antioxidant (Schlich et al., 2020; Wang, Zhao, et al., 2020), anticancer (Chaudhary et al., 2019; Lin et al., 2020; Liu et al., 2020; Yin et al., 2020), hepatoprotection (Lee et al., 2012) effects. In addition, RES can improve metabolic disorders in diabetic rats (Liohanna et al., 2020).…”