Protective effects of Ejiao on chronic obstructive pulmonary disease in mice via modulation of the ER/AKT/NF-κB pathway

Background and objectives

Chronic obstructive pulmonary disease (COPD) is an irreversible inflammatory lung disease. Studies have shown that macrophages and estrogen receptors play a pivotal regulatory role in the development of COPD. Ejiao (Colla Corii Asini, CCA, or donkey-hide gelatin), a traditional Chinese medicine, has anti-inflammatory and lung function-protective effects, but its specific mechanism in COPD remains unclear. This study aimed to explore the immunomodulatory effects of Ejiao on COPD, focusing on its impact on inflammatory pathways and macrophages.

Methods

This study is the first to apply a network pharmacology approach to explore the potential mechanisms underlying Ejiao’s therapeutic effects on COPD. We collected the peptides and chemical components of Ejiao and used the STRING database to screen for COPD-related targets of Ejiao components, constructing a drug-molecular network. Additionally, we established cigarette smoke extract (CSE) and lipopolysaccharide-induced cell injury models and treated them with Ejiao-containing serum. Western blot (WB) analysis was used to detect the expression of related proteins, enabling a preliminary exploration of Ejiao’s effects and regulatory mechanisms. In further experiments, a mouse COPD model was established, and eight weeks of Ejiao intervention were conducted. We assessed lung function, pathological changes in lung tissue, monitored cytokine levels in serum and bronchoalveolar lavage fluid, performed flow cytometry to evaluate abdominal macrophage levels, and conducted WB to analyze protein expression, providing an in-depth study of Ejiao’s regulatory effects on the mouse COPD model.

Results

The findings from the network pharmacology analysis suggest a potential regulatory role of the estrogen receptor pathway in COPD. CSE stimulation of RAW264.7 cells resulted in elevated tumor necrosis factor-α levels, decreased interleukin-10 levels, reduced expression of estrogen receptors (ERs) α and β, decreased inhibitor of NF-κB levels, and increased p-AKT levels. Following Ejiao intervention, interleukin-10, ERα+β, and inhibitor of NF-κB levels increased, while p-AKT levels decreased. Ejiao significantly improved lung function in CSE/lipopolysaccharide-induced COPD mice, reduced the number of macrophages, lowered the levels of inflammatory factors in bronchoalveolar lavage fluid, and increased estradiol levels in serum. WB results indicated that Ejiao may ameliorate lung injury in COPD by modulating the ER/AKT/NF-κB pathway.

Conclusions

Ejiao can significantly improve the lung function indicators of COPD model mice, reduce the content of inflammatory factors in bronchoalveolar lavage fluid, increase the estrogen content in serum, and reduce the number of peritoneal macrophages. HE pathological observation and Western blot analysis showed that Ejiao can improve lung injury, and its mechanism of action may involve regulating estrogen levels in the body and affecting the ER/AKT/NF-κB signaling pathway, thereby alleviating inflammatory response and improving lung injury.

Full text:

https://www.xiahepublishing.com/2835-6357/FIM-2025-00003

The study was recently published in the Future Integrative Medicine.

Future Integrative Medicine (FIM) publishes both basic and clinical research, including but not limited to randomized controlled trials, intervention studies, cohort studies, observational studies, qualitative and mixed method studies, animal studies, and systematic reviews.

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