The Plant-Derived Chalcone 2,2',5'-Trihydroxychalcone Provides Neuroprotection against Toll-Like Receptor 4 Triggered Inflammation in Microglia.
Manasi JiwrajkaAlexandra PhillipsMatt ButlerMiriam RossiJennifer M PocockPublished in: Oxidative medicine and cellular longevity (2015)
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.
Keyphrases
- inflammatory response
- anti inflammatory
- toll like receptor
- lipopolysaccharide induced
- lps induced
- oxidative stress
- induced apoptosis
- cell cycle arrest
- neuropathic pain
- nitric oxide synthase
- cerebral ischemia
- diabetic rats
- endoplasmic reticulum stress
- nuclear factor
- cell death
- poor prognosis
- nitric oxide
- rheumatoid arthritis
- spinal cord
- big data
- ms ms
- hydrogen peroxide
- spinal cord injury
- long non coding rna
- artificial intelligence
- brain injury
- blood brain barrier
- subarachnoid hemorrhage
- risk assessment
- endothelial cells
- data analysis