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image of The Protective Effect and Mechanisms of Maxing Kugan Decoction Against Oleic Acid-Induced Acute Lung Injury via Inhibition of Inflammatory Factors, Oxidative Damage, and Modulation of Intestinal Microbiota and Metabolites

Abstract

Introduction

Acute Lung Injury (ALI) is a serious complication of many diseases and can progress to Acute Respiratory Distress Syndrome (ARDS) without intervention. The current study aimed to determine the effect of Maxing Kugan Decoction (MXKGD) on an Oleic Acid (OA)-induced rat model of ALI while also exploring the regulatory effects of MXKGD on the PI3K/AKT signaling pathway and gut microbiota.

Methods

Ultra-Performance Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry (UPLC-QTOF/MS) was employed to determine the chemical ingredients of MXKGD. The therapeutic effects of different doses of MXKGD in treating OA-induced ALI were investigated using histopathology, ELISA assays, and immunofluorescence analysis. Additionally, network pharmacology and 16S rRNA sequencing were utilized to explore the underlying mechanisms of MXKGD in ALI treatment.

Results

Through UPLC-QTOF/MS analysis, a total of 104 compounds were identified in MXKGD, including flavonoids, alkaloids, triterpenoids, glycosides, organic acids, and cyclic peptides. Pharmacodynamic results demonstrated that MXKGD could mitigate histomorphological changes in OA-induced ALI, suppress inflammation and oxidative stress, while promoting the proliferation and differentiation of alveolar type II (AT II) cells to repair the alveolar epithelial-microvascular endothelial barrier. Network pharmacology, molecular docking, and subsequent experimental validation revealed that MXKGD upregulates the expression of -PI3K and -AKT proteins, thereby activating the PI3K/AKT signaling pathway. Furthermore, MXKGD rebalanced the disturbance of gut microbiota and associated metabolic levels of short-chain fatty acids (SCFAs) to regulate the inflammatory response.

Discussion

This study suggests that MXKGD exerts anti-inflammatory effects and protects the alveolar epithelial-microvascular endothelial barrier in ALI models by activating the PI3K/AKT signaling pathway and modulating the abundance of beneficial gut bacteria. However, further metabolomic experiments are required to confirm its precise mechanism of action.

Conclusion

The data indicate that MXKGD can effectively inhibit the development of ALI by reducing inflammation and regulating the balance of intestinal microbiota. MXKGD may serve as a potential new therapeutic option for treating ALI.

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2026-01-14
2026-01-27

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The Protective Effect and Mechanisms of Maxing Kugan Decoction Against Oleic Acid-Induced Acute Lung Injury via Inhibition of Inflammatory Factors, Oxidative Damage, and Modulation of Intestinal Microbiota and Metabolites
Bentham Science Publishers ; https://doi.org/10.2174/0113816128383495251119071534
/content/journals/cpd/10.2174/0113816128383495251119071534
/content/journals/cpd/10.2174/0113816128383495251119071534
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  • Article Type:     Research Article
Keywords: pneumonia ; Maxing Kugan decoction ; inflammation ; gut microbiota ; chemical ingredients ; acute lung injury

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