Sparstolonin B nano-formulation attenuates LPS-induced lung injury

Introduction Nanomedicines can improve drug delivery and efficacy while reducing side effects. Our study examines the impact of a nano-formulation of Sparstolonin B (nSsnB), a TLR-4 antagonist, on LPS-induced inflammation in RAW264.7 cells and lung injury in mice. Methods RAW264.7 cells were treated with LPS (1 μg/mL) ± nSsnB (2–64 μg/mL) for 24 h. Cell viability was assessed, cytokine levels in media were measured, and cell lysates were used to quantify NF-κB activation. C57BL/6 mice were treated with prophylactic intratracheal (IT) nSsnB (0.625 mg/kg) ± IT LPS (2.5 mg/kg). Blood and BALF were collected for cytokine, protein and cytological analysis. Lung histology was scored to evaluate lung injury. The relative abundance of MyD88 and phosphorylated NF-κB were measured in lung and HLL mice were used to measure NF-κB activation in vivo . Results nSsnB demonstrated reduced toxicity vs. free SsnB. nSsnB ameliorated the LPS-induced increase in TNF-α, IL-6 and NF-κB P65 phosphorylation in RAW264.7 cells. LPS-treated mice revealed histologic ALI, elevated BALF neutrophils/macrophages/total protein, and increased levels of TNF-α/IL-6 in both BALF and plasma. Prophylactic nSsnB attenuated all these parameters in the LPS/nSsnB group. The increased levels of MyD88 and P-NF-κB P65 in lung from LPS-treated mice were reduced in the LPS/nSsnB group and nSsnB attenuated the increase in NF-κB activation induced by IT LPS in HLL mice. Conclusion nSsnB demonstrates less toxicity than free SsnB and attenuates the effects of LPS on inflammation in RAW264.7 cells. Prophylactic nSsnB attenuates LPS-induced ALI by reducing inflammation via MyD88/NF-κB signaling pathways. Collectively these findings support the therapeutic potential of nano-formulated nSsnB for ALI treatment.