Sodium houttuyfonate prevents NiO-NPs induced lung injury in rats through the TNF-α/JAK-STAT signaling pathway.

Nickel oxide nanomaterials (NiO-NPs), as engineered nanomaterials, are frequently implicated in the onset of various inflammatory disorders. However, no specific therapeutic agent is currently available for pneumonia induced by NiO-NPs exposure. In the present study, a cytotoxicity model was established using rat type Ⅱ alveolar epithelial cells (ACE-Ⅱ) to investigate the cellular effects of NiO-NPs, while a rat model of lung injury was developed in Wistar rats via a non-exposure tracheal instillation technique. To address this pathology, we formulated a sodium houttuyfonate (SH) nanoemulsion characterized by favorable fluidity and uniform dispersion, and evaluated its therapeutic efficacy and underlying mechanisms in NiO-NPs-induced acute lung injury through three distinct administration routes: Houttuynia cordata decoction, SH tablets and SH nanoemulsion. Concurrently, network pharmacology and transcriptomic analyses were conducted to identify key molecular targets and signaling pathways. The findings demonstrated that both Houttuynia cordata and SH significantly reduced TNF-α levels and inhibited the activation of the JAK-STAT signaling pathway both in vitro and in vivo, thereby mitigating NiO-NPs-induced pulmonary injury. Among the various formulations tested, the SH nanoemulsion exhibited the most pronounced therapeutic efficacy. This study offers a promising therapeutic strategy for NiO-NPs-induced lung injury and contributes to the advancement of pharmacological interventions for nanomaterial-related inflammatory diseases.