Baicalein Attenuates Neuroinflammation in LPS-Treated BV-2 Cells by Inhibiting Glycolysis via STAT3/c-Myc Pathway

More and more evidence shows that metabolic reprogramming is closely related to the occurrence of AD. The metabolic conversion of oxidative phosphorylation into glycolysis will aggravate microglia-mediated inflammation. It has been demonstrated that baicalein could inhibit neuroinflammation in LPS-treated BV-2 microglial cells, but whether the anti-neuroinflammatory mechanisms of baicalein were related to glycolysis is unclear. Our results depicted that baicalein significantly inhibited the levels of nitric oxide (NO), interleukin-6 (IL-6), prostaglandin 2 (PGE2) and tumor necrosis factor (TNF-alpha) in LPS-treated BV-2 cells. H-1-NMR metabolomics analysis showed that baicalein decreased the levels of lactic acid and pyruvate, and significantly regulated glycolytic pathway. Further study revealed that baicalein significantly inhibited the activities of glycolysis-related enzymes including hexokinase (HK), 6-phosphate kinase (6-PFK), pyruvate kinase (PK), lactate dehydrogenase (LDH), and inhibited STAT3 phosphorylation and c-Myc expression. By using of STAT3 activator RO8191, we found that baicalein suppressed the increase of STAT3 phosphorylation and c-Myc expression triggered by RO8191, and inhibited the increased levels of 6-PFK, PK and LDH caused by RO8191. In conclusion, these results suggested that baicalein attenuated the neuroinflammation in LPS-treated BV-2 cells by inhibiting glycolysis through STAT3/c-Myc pathway.

Automated summary

More and more evidence suggests that metabolic reprogramming is closely linked to Alzheimer's disease (AD). The switch from oxidative phosphorylation to glycolysis worsens microglia-mediated inflammation. Baicalein has been shown to inhibit neuroinflammation in BV-2 microglial cells treated with LPS, but its mechanism of action in relation to glycolysis is unclear. Our results demonstrate that baicalein significantly reduces the levels of nitric oxide (NO), interleukin-6 (IL-6), prostaglandin-2 (PGE2), and tumor necrosis factor (TNF-alpha) in LPS-treated BV-2 cells. H-1-NMR metabolomics analysis reveals that baicalein decreases the levels of lactic acid and pyruvate, and effectively regulates the glycolytic pathway. Further investigation reveals that baicalein inhibits the activity of glycolysis-related enzymes and suppresses STAT3 phosphorylation and c-Myc expression. By using a STAT3 activator, RO8191, we found that baicalein hinders the increase in STAT3 phosphorylation and c-Myc expression triggered by RO8191, and also inhibits the elevated levels of 6-PFK, PK, and LDH caused by RO8191. In conclusion, these findings suggest that baicalein alleviates neuroinflammation in LPS-treated BV-2 cells by inhibiting glycolysis through the STAT3/c-Myc pathway.