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.