Interventional Effects of Grape Skin Extract against Lung Injury Induced by Artificial Fine Particulate Matter in a Rat Model

Abstract

Background and objectives: The mechanism underlying lung injury due to atmospheric fine particulate matter (PM2.5) remains unclear, and currently, there are no medications for specific intervention.

Methods: Different doses of grape skin extract (GSE, 0.1, 0.2, and 0.4 g/kg, respectively) were administered prophylactically to the treatment groups, while sterile water was administered to the control and model groups. PM2.5 in suspension (1 mL at 30 mg/kg) was administered twice weekly for six weeks. The rats were sacrificed 48 h after the last administration. Pulmonary function was assessed weekly by a whole-body plethysmography system. Hematoxylin-eosin staining, alveolar lavage fluid leukocyte classification and counts, detection of cytokines with an enzyme-linked immunosorbent assay, and other methods were employed to evaluate pathological changes and inflammation of the lungs, amino acid metabolomics, and lipid metabolomics. A gene chip was used for mRNA profiling to identify potential drug targets.

Results: Lung function was diminished compared to the control group. Pathological changes were significant, and lung inflammation was more evident in the model group. There were also apparent changes in lung tissues and serum metabolites of amino acids and lipids. The lung function, the inflammatory response, fibrosis, and the number of phagocytes of the lung interstitium were significantly improved with GSE treatment. Local inflammation of lung tissue was reduced. Serum, lung tissue amino acids, and lipid metabolites underwent dramatic corrections. Functional enrichment analysis found that GSE improved the lung damage caused by PM2.5 via the complement and oxidative phosphorylation pathways.

Conclusions: GSE significantly improved lung injury and pulmonary inflammation induced by PM2.5 in rats. The detection results of multiple omics provided important information for subsequent comprehensive clarification of potential targets and intervention mechanisms of GSE.

Keywords

Grape skin extract / Artificial fine particulate matter / Lung injury / Interventional effect

Acknowledgement

Special thanks to Professor Zhongze Fang for his great support and help in metabonomics detection and Professor Hong Yang for her great support and help in transcriptomics detection.

Funding

This study was financially supported by the National Natural Science Foundation of China (grant no. 82074104), the Chinese Academy of Medical Sciences-CAMS Innovation (grant no. CAMS-I2M), and the Chinese Society of Toxicology (grant no. CST2021CT101), Discipline Construction Project of Peking Union Medical College (grant number: 201920200801).

Conflict of interest

HTJ has been an editorial board member of Future Integrative Medicine since November 2021. The other authors declare that they have no conflict of interest related to this publication.

Authors’ contributions

Conception and design (HTJ and PCZ); Administrative support (HTJ and PCZ); Provision of study materials or patients (HTJ, PCZ, JB, and JL); Collection and assembly of data (YHL, ZGL, SZL, HYJ, and LK); Data analysis and interpretation (ZGL, YHL, SZL, HYJ, and LK); Manuscript composition: All authors; Final approval of manuscript: All authors.

Ethical Statement

The animal test has been approved by the Center for Beijing Union-Genius Pharmaceutical Technology Development Co. Ltd. Ethical Approval No.: 2017-0000242. The protocol was approved by the Center for Beijing Union-Genius Pharmaceutical Technology Development Co. Ltd., and the procedures followed the approved guidelines. All animals were euthanized using CO₂ gas in a special chamber, and all efforts were made to minimize suffering.

Data sharing statement

The data used in supporting the findings of this study are included within the article.

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