From Yufeining to Kaempferol: Multi-Target Anti-Inflammatory, Antioxidant, and Anti-Apoptotic Mechanisms Targeting the STAT3-TP53-IL1B Signaling Network in COPD Therapy
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Xiubo Li1, Jiacheng Shi1, Liyuan Pang2
1Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
Background:
Chronic obstructive pulmonary disease (COPD) is a heterogeneous syn-drome which leads to irreversible and progressive airflow limitation. Yufeining (YFN) is a Chinese herbal formula employed for treating COPD; however, the key ingredients and mechanisms are not fully defined.
Methods:
The key bioactive compounds and their corresponding targets of YFN were recognized using the network pharmacology method. The CIBERSORT algorithm was employed to identify the immune infiltration profiles in COPD and their correlation with the principal targets. Through the COPD mouse model, the effects of kaempferol on inflammation, oxidative damage, and apoptosis were evaluated. The BEAS-2B cells treated with cigarette smoke extract (CSE) were used to assess the protective effects of kaempferol against inflammation, oxidative stress, and apoptosis. Using flow cytometry, the anti-apoptosis effects of kaempferol were analyzed. Transcriptomic Analysis was performed to investigate the transcriptional changes in CSE-induced BEAS-2B cells.
Results:
Kaempferol is a key compound of YFN, and STAT3, TP53, and IL1B are predicted to be the core targets of YFN for COPD treatment. Immune infiltration analysis revealed a significant correlation between STAT3-TP53-IL1B signaling network and inflammatory cell infiltration. Kaempferol alleviated inflammation, oxidative damage, and apoptosis in the COPD mouse model. In CSE-induced BEAS-2B cells, kaempferol inhibited the inflammatory response, oxidative damage, and apoptosis. The transcriptome sequencing revealed a total of 223 differentially expressed genes. After treating with kaempferol, the transcriptional levels of STAT3 significantly increased, while those of TP53 and IL1B significantly decreased.
Conclusions:
Kaempferol can exert therapeutic effects against COPD by inhibiting inflammatory response and oxidative damage, and reducing cell apoptosis. Furthermore, this study indicated the therapeutic mechanism of YFN in COPD involves potentially targeting the STAT3-TP53-IL1B signaling network through kaempferol.
