Laggera alata attenuates LPS‑induced systemic inflammation and hepatic‑pulmonary injury by regulating PINK1/Parkin-associated mitophagy and macrophage polarization

Laggera alata is a traditional medicinal herb used for inflammatory and infectious diseases, but its mechanisms against endotoxin-induced systemic inflammation remain unclear.The present study investigated the protective effects of total phenolics from Laggera alata (TPla) on lipopolysaccharide (LPS)-induced inflammatory injury and explored the involvement of PTEN-induced putative kinase 1 (PINK1)/Parkin-associated mitophagy and macrophage polarization.LPS-induced inflammatory models were established in raW264.7 macrophages and c57Bl/6 mice.Cell viability, apoptosis, mitochondrial membrane potential (MMP), cytokine production, macrophage polarization and mitophagy-related protein expression were evaluated.Mdivi-1 was used to assess the involvement of mitophagy-related signaling.In vivo, core body temperature, serum cytokines, and lung and liver histopathology were examined.TPLA improved the viability of LPS-stimulated macrophages, reduced apoptosis, restored MMP, decreased p62 expression, and increased PinK1, Parkin and the lc3-ii/lc3-i ratio.TPla also suppressed M1-associated indicators, including inducible nitric oxide synthase, IL-12 and cd80/cd86, while enhancing M2-associated indicators, including arginase 1, il-10 and cd206/cd163.in addition, TPla reduced il-1β, il-6 and TnF-α release.Mdivi-1 partially reversed the effects of high-dose TPLA on mitophagy-related protein expression and macrophage polarization.In LPS-challenged mice, TPLA alleviated hypothermia, reduced systemic cytokine levels, and attenuated hepatic and pulmonary injury.These findings suggest that TPLA protects against LPS-induced systemic inflammation and hepatic-pulmonary injury by modulating PINK1/Parkin-associated mitophagy-related signaling and macrophage polarization.