The Pharmacological Material Basis and Potential Mechanism of Qingre Bawei Capsule in Alleviating Acute Lung Injury Induced by LPS in Mice.
TL;DR
It is demonstrated that QRBW clearly ameliorates LPS-induced inflammatory injury in ALI mouse model and Corynoline and acetylcorynoline were identified as the key bioactive constituents underlying this effect.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Qingre Bawei capsules (QRBW), derived from the traditional Mongolian medicine Erhemu-8 (-8), have been clinically used to treat respiratory infections associated with lung heat syndrome, including pneumonia, bronchitis, influenza, and acute lung injury (ALI). However, its specific effects and underlying mechanisms in ALI remain unclear.
Aim
OF THE STUDY This study aimed to evaluate the therapeutic effects of QRBW on lipopolysaccharide (LPS)-induced ALI and to identify its active constituents and mechanisms using serum pharmacochemistry, transcriptomics, and biological validation.
Materials And Methods
An in vivo LPS-induced acute lung injury (ALI) mouse model was employed to evaluate the ameliorative effects of QRBW after oral administration. The parameters assessed included body weight changes, pulmonary function, total protein concentration in bronchoalveolar lavage fluid (BALF), the lung wet-to-dry (W/D) weight ratio, levels of IL-6, IL-1β, and TNF-α in BALF, and histopathological examination of lung tissue. Subsequently, UHPLC-Q-Exactive HRMS was applied to identify the chemical constituents absorbed into the bloodstream. Network pharmacology was then used to narrow down the candidate compounds, followed by in vitro anti-inflammatory screening to pinpoint the active components. Furthermore, transcriptomic analysis of lung tissue, Western blotting, quantitative real-time PCR (qRT-PCR), and molecular docking were performed to explore and validate the key signaling pathways through which QRBW alleviates ALI-associated inflammatory injury.
Results
QRBW significantly ameliorated lung function impairment in an LPS-induced ALI mouse model after oral administration at doses of 620 and 1,240 mg/kg. Additionally, QRBW reduced the lung W/D weight ratio and total protein concentration in BALF, markedly suppressed the release of IL-6, IL-1β, and TNF-α into BALF, and attenuated inflammatory cell infiltration in lung tissue. These findings demonstrate that QRBW clearly ameliorates LPS-induced inflammatory injury in ALI mouse model. Following oral administration of QRBW, twenty compounds were identified in the bloodstream using UHPLC-Q-Exactive HRMS. Corynoline and acetylcorynoline were identified as the key active components responsible for the therapeutic effect of QRBW on ALI. QRBW modulates the JAK-STAT signaling pathway, as evidenced by the downregulation of p-JAK1 and p-STAT3 expression and reduced mRNA levels of the downstream inflammatory cytokines Il6, Il1b, and Tnf. Molecular docking analysis further showed that both corynoline and acetylcorynoline exhibit favorable binding affinities for JAKs and STATs.
Conclusion
QRBW can ameliorate LPS-induced ALI by attenuating the inflammatory response. Corynoline and acetylcorynoline were identified as the key bioactive constituents underlying this effect. The mechanism involves inhibition of the JAK-STAT signaling pathway, as demonstrated by the downregulation of p-JAK1 and p-STAT3 and the reduced expression of downstream inflammatory cytokines.