4.7 Article

Ruscogenin attenuates particulate matter-induced acute lung injury in mice via protecting pulmonary endothelial barrier and inhibiting TLR4 signaling pathway

期刊

ACTA PHARMACOLOGICA SINICA
卷 42, 期 5, 页码 726-734

出版社

NATURE PUBL GROUP
DOI: 10.1038/s41401-020-00502-6

关键词

ruscogenin; particulate matter; acute lung injury; bronchoalveolar lavage fluid; toll like receptor 4; endothelial permeability

资金

  1. National Natural Science Foundation of China [81773971]
  2. Double First-Class University Project of China Pharmaceutical University [CPU2018GF07]

向作者/读者索取更多资源

The active ingredient ruscogenin in Ophiopogonis japonicus was found to effectively alleviate particulate matter-induced acute lung injury by reducing pathological damage, lung edema, and vascular leakage, as well as inhibiting the TLR4/MyD88 signaling pathway.
The inhalation of particulate matter (PM) is closely related to respiratory damage, including acute lung injury (ALI), characterized by inflammatory fluid edema and disturbed alveolar-capillary permeability. Ruscogenin (RUS), the main active ingredient in the traditional Chinese medicineOphiopogonis japonicus, has been found to exhibit anti-inflammatory activity and rescue LPS-induced ALI. In this study, we investigated whether and how RUS exerted therapeutic effects on PM-induced ALI. RUS (0.1, 0.3, 1 mg center dot kg(-1)center dot d(-1)) was orally administered to mice prior to or after intratracheal instillation of PM suspension (50 mg/kg). We showed that RUS administration either prior to or after PM challenge significantly attenuated PM-induced pathological injury, lung edema, vascular leakage and VE-cadherin expression in lung tissue. RUS administration significantly decreased the levels of cytokines IL-6 and IL-1 beta, as well as the levels of NO and MPO in both bronchoalveolar lavage fluid (BALF) and serum. RUS administration dose-dependently suppressed the phosphorylation of NF-kappa B p65 and the expression of TLR4 and MyD88 in lung tissue. Furthermore, TLR4 knockout partly diminished PM-induced lung injury, and abolished the protective effects of RUS in PM-instilled mice. In conclusion, RUS effectively alleviates PM-induced ALI probably by inhibition of vascular leakage and TLR4/MyD88 signaling. TLR4 might be crucial for PM to initiate pulmonary lesion and for RUS to exert efficacy against PM-induced lung injury.

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