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.
Keywords: Acute respiratory distress syndrome; Lung first-pass effect; Pharmacokinetics; Sepsis-associated acute lung injury; Tanreqing injection.
Copyright © 2024 Elsevier B.V. All rights reserved.