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Updated: Feb 20, 2026
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Polidatina atenúa la lesión pulmonar aguda inducida por LPS en ratas dirigiéndose a HSP90AB1
Liang Han1, Ziye Shi2, Fancui Meng3
1State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Quality Marker of Traditional Chinese Medicine, National & Local United Engineering Laboratory of Modern Preparation and Quality Control Technology of Traditional Chinese Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin 300462, China; Heguang TCM Technology (Tianjin) Co., Ltd., Tianjin 300462, China.
Ethnopharmacological Relevance:
The root of Polygonum cuspidatum Sieb. et Zucc, referred to as Huzhang in traditional Chinese medicine, is widely employed in therapeutic formulations against inflammatory diseases. As its core bioactive constituent, polydatin (PD), exhibits anti-inflammatory, antioxidant, and immunomodulatory effects. Despite these pharmacological properties, the molecular targets underpinning PD's anti-inflammatory actions in pulmonary disorders remain unclear.
Purpose:
This study aims to identify therapeutic targets and elucidate the molecular mechanisms of PD against acute lung injury (ALI).
Materials And Methods:
In a rat model of ALI induced by LPS, PD was administered at doses of 10, 20, and 40 mg/kg for 7 consecutive days to evaluate therapeutic efficacy. Integrated approaches including Cellular Thermal Shift Assay (CETSA), Thermal Proteome Profiling (TPP), mass spectrometry, site-directed mutagenesis, molecular docking, molecular dynamics simulations, Fluorescence-based Thermal Shift Assay (FTS) and Microscale Thermophoresis (MST) identified potential target proteins and binding sites. Subsequently, RAW264.7 cell lines overexpressing the target protein were established to investigate its regulatory effects on inflammatory pathways. Cellular/tissue co-localization, Western blotting, and immunohistochemistry (IHC) further revealed that PD targets HSP90AB1 and modulates the IL-17 signaling pathway.
Results:
we established that PD significantly attenuates LPS-induced inflammatory responses in vivo and in vitro. Subsequently, we verified that PD specifically targets HSP90AB1 through binding to its Asp88 residue. Critically, mechanistic studies revealed that PD binding disrupts HSP90AB1-mediated stabilization of the client protein ACT1, thereby suppressing the IL-17 signaling pathway.
Conclusion:
Polydatin confers protection against ALI in rat models by targeting HSP90AB1 and suppressing the IL-17 signaling pathway.
