Celastrus orbiculatus Thunb. extract inhibits inflammatory metabolic adaptation in macrophages and regulates polarization via modulating PKM2.

Precancerous lesions of gastric cancer (PLGC) are considered critical stages for the prevention and treatment of gastric cancer (GC), with gastric mucosal inflammation being a prerequisite for PLGC. Macrophages, integral to the immune system, typically respond to external stimuli triggering inflammation. Celastrus orbiculatus Thunb. extract (COE) has been shown to exhibit anti-inflammatory effects in treating PLGC. However, it remains unclear how COE modulates macrophage metabolic adaptation and polarization in the inflammatory response to reverse PLGC. This study utilized a composite modeling approach to establish a PLGC mouse model, assessing COE's impact on polarization and metabolic adaptation markers such as inflammatory factors in gastric mucosa and RAW264.7 macrophages. The results confirm that COE significantly reduces M1 macrophage polarization markers while increasing M2 macrophage polarization markers and lowering inflammatory factor levels. Additionally, COE effectively inhibits the expression of pyruvate kinase M2 (PKM2). Our findings suggest that COE may act through regulating PKM2 expression to modulate inflammatory responses and reverse PLGC.