Ethyl acetate fraction from Dendrobium officinale inhibits IL-17A signaling pathway to mitigate acute lung injury.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium officinale Kimura et Migo (D. officinale), a rare and precious orchid (Orchidaceae) in traditional Chinese medicine, exhibits a sweet flavor and a cold nature, and acts on lung, stomach, and kidney meridians with marked efficacy in nourishing lung yin. When applied medicinally and in functional foods, it demonstrates antioxidant, immunomodulatory, anti-inflammatory, and anti-inflammatory, and antitumor bioactivities. AIM OF THE STUDY: This study aimed to investigate the role and mechanisms of action of an ethyl acetate extract of D. officinale (DOEA) in the treatment of acute lung injury (ALI). MATERIALS AND METHODS: The pharmacological effects of DOEA extract were evaluated using lipopolysaccharide (LPS)-induced ALI models in vivo and RAW264.7 cell models in vitro. Transcriptomic profiling was performed via RNA sequencing to elucidate the mechanism by which DOEA protects against LPS-induced injury. ALI Furthermore, the protective effects of DOEA against LPS-induced ALI and cellular inflammatory responses were comprehensively evaluated through histology, lung index assessment, immunofluorescence, immunohistochemistry, Western blotting, quantitative real-time PCR, and flow cytometry. Exploring the anti-inflammatory effects of DOEA on the IL-17A signaling pathway was achieved by knocking down IL-17RA in RAW264.7 cells via siRNA interference technology, as well as by conducting exogenous IL-17A stimulation experiments. RESULTS: DOEA mitigated LPS-induced ALI by attenuating pulmonary cytokine expression, suppressing NF-κB pathway activation, and reducing oxidative tissue damage via the inhibition of cellular oxidative stress. Moreover, the efficacy of DOEA against ALI was significantly associated with the targeting of IL-17RA. Notably, IL-17RA knockdown significantly alleviated the LPS-induced inflammatory response in RAW264.7 cells. Furthermore, DOEA was able to suppress the inflammatory response induced by exogenous IL-17A stimulation in these cells. CONCLUSION: DOEA alleviates LPS-induced acute lung injury and cellular inflammatory responses by inhibiting the IL-17 signaling pathway.