The Plant-Derived Chalcone 2,2',5'-Trihydroxychalcone Provides Neuroprotection against Toll-Like Receptor 4 Triggered Inflammation in Microglia

Oxidative Medicine and Cellular Longevity
Manasi JiwrajkaJennifer M Pocock

Abstract

Chalcones are plant metabolites with potential for therapeutic exploitation as antioxidant, anti-inflammatory, and antiproliferative agents. Here we explored the neuroprotective effects of 2,2',5'-trihydroxychalcone (225THC), a potent antioxidant with radical-scavenging properties. 225THC was found to be a potent inhibitor of apoptosis in stimulated primary rat neuronal cultures. This was likely mediated by an anti-inflammatory effect on microglial cells since 225THC inhibited LPS-stimulated TNF-α and IL-6 secretion from primary rat microglia and modulated the cytokine/chemokine profile of BV2 microglial cells. Additionally, 225THC inhibited LPS-evoked inducible nitric oxide synthase expression but did not influence endogenous superoxide generation. Microglial flow cytometric analyses indicated the 225THC treatment induced a shift from an M1-like phenotype to a more downregulated microglial profile. Taken together these data suggest that the chalcone 2,2',5'-trihydroxychalcone can modulate neuroinflammatory activation in brain-derived microglia and holds promise as a therapeutic in neuroinflammatory conditions.

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Citations

Feb 12, 2021·Bioorganic Chemistry·Pritam ThapaMukut Sharma
Dec 3, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hyejin ParkStephen Safe
Nov 2, 2020·Bioorganic Chemistry·Pichjira SooknualVirapong Prachayasittikul

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Methods Mentioned

BETA
Fluorescence Imaging
fluorescence microscopy
ELISA
flow cytometry
PMA

Software Mentioned

Flowing
Image J
Zeiss Axiovision Imaging System

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