Anti-inflammatory effects of JI-017 in cellular and an LPS-induced endotoxemia model

Abstract

Sepsis is a life-threatening condition characterized by dysregulated inflammatory responses and excessive cytokine production, leading to multi-organ dysfunction. Despite advances in supportive care, effective pharmacological strategies to directly modulate sepsis-associated inflammation remain limited. JI-017 is a multi-herbal formulation composed of Angelica gigas, Aconitum carmichaeli Debeaux, and Zingiber officinale Roscoe (2:1:1), previously studied for its anticancer properties. The anti-inflammatory effects of JI-017 were evaluated using an integrative approach combining in silico analysis, in vitro macrophage assays, and an in vivo lipopolysaccharide (LPS)-induced endotoxemia model. RAW 264.7 macrophages were used to assess nitric oxide production, cytokine expression, and inflammatory signaling pathways. In vivo effects were evaluated through survival analysis, serum cytokine measurement, and histopathological examination. JI-017 significantly reduced nitric oxide production and suppressed inflammatory cytokine and chemokine expression in LPS-stimulated RAW 264.7 macrophages. In vivo, JI-017 was associated with improved survival and attenuated systemic and hepatic inflammatory responses in an LPS-induced endotoxemia model. Under the experimental conditions examined, JI-017 did not reduce LPS-induced phosphorylation of the selected MAPK and NF-κB signaling proteins. Under the experimental conditions examined, JI-017 reduced inflammatory responses and was associated with improved survival in an acute LPS-induced endotoxemia model. These findings support further preclinical investigation of JI-017.