Standardized Sechium edule root extract attenuates LPS inflammation alongside transient STAT3 phosphorylation and an interleukin 10 biased macrophage response

Chronic low-grade inflammation is sustained by macrophage activation toward proinflammatory states and contributes to cardiometabolic and degenerative disorders. Given the growing interest in evidence-based medicinal plants, we investigated whether a hydroalcoholic root extract of Sechium edule (rSe-HA) attenuates LPS-induced macrophage inflammatory activation and modulates selected cytokine, surface-marker, functional, and signaling parameters under persistent in vitro inflammatory stimulation. Murine RAW 264.7 macrophages were activated with lipopolysaccharide (LPS) and treated with cinnamic acid-standardized rSe-HA. In culture supernatants, nitrite was quantified as an indirect index of nitric oxide production, and cytokines (TNF-α, IL-6, IL-1β, IL-10, TGF-β, and IL-4) were measured by immunoassays; the IL-10/TGF-β ratio was calculated as an exploratory indicator of cytokine balance. F4/80, CD86, and CD206 expressions and phagocytosis of latex beads were assessed by flow cytometry. STAT3 phosphorylation was assessed by immunoblotting, and NF-κB/AP-1-dependent reporter activity was examined in RAW-Blue reporter macrophages. rSe-HA reduced nitrite, TNF-α, and IL-6 levels; limited the increase in LPS-induced CD86, whereas it favored the increase of CD206 and partially restored phagocytic activity. Additionally, rSe-HA was associated with a transient increase in STAT3 phosphorylation and reduced NF-κB/AP-1-dependent reporter activity. These findings support an IL-10-biased immunomodulatory response rather than definitive assignment to a specific macrophage subtype. Further studies in primary macrophages and additional mechanistic models are needed to validate these in vitro findings.