Acacetin Attenuates Heatstroke-Induced Acute Liver Injury by Targeting the c-Jun/PTGS2 Pathway

Area of Science:

• Hepatology
• Pharmacology
• Oxidative Stress Research

Background:

• Heatstroke-induced acute liver injury (HS-ALI) is a critical condition driven by oxidative stress and inflammation.
• Acacetin (AC), a natural flavone, possesses known antioxidant and anti-inflammatory properties but its role in HS-ALI was unexplored.
• Understanding AC's mechanism in HS-ALI is crucial for developing novel therapeutic strategies.

Purpose of the Study:

• To investigate the efficacy of Acacetin (AC) in ameliorating heatstroke-induced acute liver injury (HS-ALI).
• To elucidate the underlying molecular mechanisms of AC's protective effects against HS-ALI.
• To evaluate AC's impact on oxidative stress, inflammation, the c-Jun/PTGS2 pathway, and ferroptosis in HS-ALI.

Main Methods:

• Integrated network pharmacology, molecular docking, and molecular dynamics simulations to identify AC's core targets (JUN and PTGS2).
• Conducted in vivo experiments using mice subjected to heatstroke, with or without AC pretreatment.
• Assessed liver injury, oxidative stress markers, c-Jun/PTGS2 pathway activation, and ferroptosis using histopathology, Western blot, and qPCR.

Main Results:

• Acacetin (AC) pretreatment significantly reduced heatstroke-induced liver damage and oxidative stress in mice.
• AC suppressed the activation of the c-Jun/PTGS2 signaling pathway, a key mediator of HS-ALI.
• AC inhibited key markers of ferroptosis, indicating a role in preventing this cell death pathway in HS-ALI.

Conclusions:

• Acacetin (AC) demonstrates significant therapeutic potential for heatstroke-induced acute liver injury (HS-ALI).
• AC ameliorates HS-ALI by inhibiting the c-Jun/PTGS2 axis and attenuating ferroptosis.
• Further investigation into AC as a candidate compound for HS-ALI treatment is warranted.