TFEB Activator Curcumin Analog C1 Downregulates PKM2 and Alleviates Inflammatory Injury in Endotoxemic Mice.

OBJECTIVE

Autophagy dysfunction results in the accumulation of pro-inflammatory components and drives inflammatory injury. Transcription factor EB (TFEB) is a master regulator of autophagy and a novel target for controlling inflammatory injury. Curcumin analog C1 directly binds to and activates TFEB, but its anti-inflammatory effects remain unclear.

METHODS

The anti-inflammatory and protective effects of curcumin analog C1 were investigated in lipopolysaccharide (LPS)-induced endotoxemia mice.

RESULTS

Curcumin analog C1 reversed LPS-induced autophagy dysfunction, downregulated pyruvate kinase M2 (PKM2), and reduced pro-inflammatory cytokines including TNF-α, IL-6, and MCP-1. It also attenuated systemic abnormalities, alleviated lung injury, and decreased blood urea nitrogen (BUN), brain-type natriuretic peptide (BNP), and extracellular DNA levels.

CONCLUSIONS

Curcumin analog C1 exhibits potential pharmacological value in the control of inflammatory injury.Thank you for your assistance.