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Exploratory research on the effective chemical basis of tanreqing injection for treating acute lung injury: In vivo, in vitro and in silico

  • Bixi Tang
  • , Like Xie
  • , Yangyang Wang
  • , Yulong Shi
  • , Weijuan Kan
  • , Bo Feng
  • , Chenxuan Lin
  • , Zhijian Xu
  • , Weiliang Zhu
  • , Jia Li*
  • , Xuemei Zhang*
  • , Xiaoting Tian*
  • , Yi Zang*
  • *此作品的通讯作者
  • Fudan University
  • CAS - Shanghai Institute of Materia Medica
  • University of Chinese Academy of Sciences
  • Bohai Rim Advanced Research Institute for Drug Discovery
  • Lingang Laboratory

科研成果: 期刊稿件文章同行评审

摘要

Ethnopharmacological relevance: Sepsis-induced acute lung injury (ALI) presents with significant morbidity and mortality in clinical settings. Tanreqing Injection (TRQI) has been clinically recommended for the treatment of ALI; however, the specific active chemical constituents remain unidentified. Aim of the study: This study aimed to elucidate the potential pharmacologically active components and the underlying mechanisms of TRQI in the treatment of sepsis-induced ALI. Materials and methods: High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) techniques were employed to identify the effective chemical constituents of TRQI. Additionally, an in vitro study was conducted using Raw264.7 macrophage cells stimulated with lipopolysaccharide (LPS) to evaluate the inhibitory effects of TRQI. An acute lung injury model produced by LPS was intraperitoneal injection in mice to assess the ALI-inhibitory effect of TRQI. The lung's pathological characteristics were examined using hematoxylin and eosin staining. Enzyme-linked immunosorbent assay (ELISA) and QPCR were performed to confirm the pharmaceutical effect. Network pharmacology was employed for mechanistic exploration, incorporating GO, and PPI analyses of targets. Src inhibitor and JNK agonist used to investigate the dependence of associated signaling pathways. Results: Combining pharmacokinetic characteristics, lung first-pass effect and anti-inflammatory effects, the main components of TRQI for treating sepsis induced ALI were narrowed down to seven compounds: chlorogenic acid, scutellarin, wogonoside, oroxyloside, oroxylin A and baicalein. Network pharmacology indicated that Src/JNK signaling pathway, may be the main regulatory pathway for treatment of actue lung injury. Next by using Src inhibitor, Src inhibition partly diminished the protective effects of TRQI in LPS-injected mice. Pretreatment with JNK agonist anisomycin abolished the protective effects of lung injury in vivo. Conclusions: TRQI is injected, the seven compounds could be presented in vivo, which can improve ALI by inhibiting Src-JNK signaling.

源语言英语
文章编号118780
期刊Journal of Ethnopharmacology
337
DOI
出版状态已出版 - 30 1月 2025
已对外发布

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