Terminalia chebula Extract Alleviates Lipopolysaccharide-Induced Acute Lung Injury by Modulating the...

Area of Science:

• Pharmacology and Toxicology
• Immunology
• Natural Product Chemistry

Background:

• Acute lung injury (ALI) is a severe inflammatory condition linked to interleukin-17 (IL-17) dysregulation.
• Traditional medicinal plants like Terminalia chebula Retz. (TCE) show potential in modulating inflammatory responses.

Purpose of the Study:

• To evaluate the prophylactic effect of TCE on lipopolysaccharide (LPS)-induced ALI in a mouse model.
• To elucidate the underlying IL-17-linked mechanisms of TCE's therapeutic action.

Main Methods:

• Established a mouse model of LPS-induced ALI for efficacy assessment.
• Utilized Liquid Chromatography-Mass Spectrometry (LC-MS) for phytochemical analysis and absorbed component identification.
• Employed network pharmacology, molecular docking, and dynamics simulations for target prediction.
• Validated key findings using Western blot and immunohistochemistry.

Main Results:

• TCE pretreatment significantly alleviated lung tissue damage and reduced pro-inflammatory cytokines (IL-6, TNF-α, IL-17A) in ALI mice.
• TCE suppressed the enhanced alveolar expression of IL-17.
• LC-MS identified 55 TCE constituents, with 15 bioactive compounds, including ellagic acid, found in circulation.
• Computational analyses confirmed stable interactions between key compounds (ellagic acid) and core targets (IL-6, CXCL8).
• KEGG analysis revealed enrichment in IL-17 and NF-κB signaling pathways.
• TCE inhibited the IL-17-MAPK/NF-κB pathway, decreasing phosphorylation of p65, p38, IκBα, and downregulating TLR4, MyD88, iNOS, and COX-2.

Conclusions:

• TCE pretreatment demonstrates significant therapeutic potential in mitigating LPS-induced ALI.
• TCE modulates the IL-17-dependent signaling axis, enhancing inflammation resolution and reducing lung injury.
• Targeting the IL-17-MAPK/NF-κB pathway is a key mechanism for TCE's beneficial effects in ALI.