Oxyresveratrol Inhibits IL-1β-Induced Inflammation via Suppressing AKT and ERK1/2 Activation in Human Microglia, HMC3

Abstract

Oxyresveratrol (OXY), a major phytochemical component derived from several plants, has been proved to have several pharmacological properties. However, the role of OXY in regulating neuroinflammation is still unclear. Here, we focused mainly on the anti-neuroinflammatory effects at the cellular level of OXY in the interleukin-1 beta (IL-1β)-stimulated HMC3 human microglial cell line. We demonstrated that OXY strongly decreased the release of IL-6 and MCP-1 from HMC3 cells stimulated with IL-1β. Nevertheless, IL-1β could not induce the secretion of TNF-α and CXCL10 in this specific cell line, and that OXY did not have any effects on reducing the basal level of these cytokines in the sample culture supernatants. The densitometry analysis of immunoreactive bands from Western blot clearly indicated that IL-1β does not trigger the nuclear factor-kappa B (NF-κB) signaling. We discovered that OXY exerted its anti-inflammatory role in IL-1β-induced HMC3 cells by suppressing IL-1β-induced activation of the PI3K/AKT/p70S6K pathway. Explicitly, the presence of OXY for only 4 h could strongly inhibit AKT phosphorylation. In addition, OXY had moderate effects on inhibiting the activation of ERK1/2. Results from immunofluorescence study further confirmed that OXY inhibited the phosphorylation of AKT and ERK1/2 MAPK upon IL-1β stimulation in individual cells. These findings suggest that the possible anti-inflammatory mechanisms of OXY in IL-1β-induced HMC3 cells are mainly through its ability to suppress the PI3K/AKT/p70S6K and ERK1/2 MAPK signal transduction cascades. In conclusion, our study provided accumulated data that OXY is able to suppress IL-1β stimulation signaling in human microglial cells, and we believe that OXY could be a probable pharmacologic agent for altering microglial function in the treatment of neuroinflammation.

Oxyresveratrol Inhibits R848-Induced Pro-Inflammatory Mediators Release by Human Dendritic Cells Even When Embedded in PLGA Nanoparticles

“…(Moraceae), which has been used in Thai traditional medicine as an antioxidant and to treat inflammatory and parasitic diseases [ 30 , 31 , 32 ]. Recently, many studies have been performed to investigate the pharmacological effects of oxyresveratrol: in particular, it has been reported to suppress lipopolysaccharide-induced inflammatory response in murine models [ 31 , 33 , 34 ] and to exert its anti-inflammatory effects mainly by downregulating the release of various cytokines [ 12 , 13 , 14 , 15 ]. As far as we know, no investigations have been made on the effect of oxyresveratrol on the functional activity of human DCs, which play an essential role in activation of inflammation and immune reaction [ 1 , 2 , 3 ].…”

“…The mechanism by which oxyresveratrol inhibits the secretion of cytokines by human DCs remains to be clarified. However, on the basis of previous reports showing that this polyphenol decreased the release of cytokines from HMC3 human microglial and RAW 264.7 murine macrophage cell lines through inhibition of phosphatidylinositol 3-kinase [ 15 , 31 ], it is conceivable that a similar mechanism might also take place in human DCs.…”

“…Interestingly, DC treated with the polyphenol resveratrol during their differentiation have been reported to became tolerogenic cells showing decreased ability to stimulate T cells because of a reduced expression of co-stimulatory molecules and IL-12, and an increased secretion of the immune suppressive cytokine IL-10 [ 10 ]. Moreover oxyresveratrol, a polyphenol derived from Artocarpus lakoocha Roxb.heartwood, a plant known in Thai as ‘Ma-Haad’ and used in traditional medicine [ 11 ], has been shown to exert anti-inflammatory effects by downregulating the pro-inflammatory cytokine production in several experimental conditions [ 12 , 13 , 14 , 15 ]. However, the mechanisms by which polyphenols exert their anti-inflammatory activity remain to be fully elucidated and, as far as we know, no investigations have been performed on the effect of oxyresveratrol on the functional activity of human DCs.…”

Proteomic Analysis of Rhesus Macaque Brain Explants Infected With Borrelia Burgdorferi Identifies Host GAP-43 As A Potential Factor Associated With Lyme Neuroborreliosis

“…Spirochetes have been detected at nerve roots in a rhesus macaque model of LNB [23]. The HMC3 cell line was established through SV40-dependent immortalisation of human embryonic microglia and was recently authenticated by the American Type Culture Collection (ATCC CRL-3304; Manassas, VA, USA), and has been used in several studies [9,24,25].…”

Plant-Based Bioactive Molecules in Improving Health and Preventing Lifestyle Diseases

“…The anti-inflammatory effect of the stilbenoid oxyresveratrol was also observed in the human microglial cell line HMC3. The effect is mediated by suppressing the PI3K/AKT/p70S6K and ERK1/2 MAPK signaling pathways [ 7 ].…”