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Cistanche deserticola polysaccharide alleviates bronchiectasis by regulating arginine metabolism and STAT signaling
Wei Lu1, Shaochu Zheng2, Yun Jiang2
1The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou 545002, China; Guangxi Medical University, Nanning 530021, China.
Abstract:
The present study aimed to explore the regulatory mechanisms through which Cistanche deserticola polysaccharide (CDP) ameliorates immune-metabolic dysregulation in an experimental bronchiectasis model. Bronchiectasis was induced in six-month-old female Sprague-Dawley (SD) rats through intratracheal administration of Pseudomonas aeruginosa. The experimental animals were divided into multiple groups: sham-operated controls, disease-induced models, low-dose and high-dose CDP treatment cohorts, as well as a positive control group treated with prednisone. After 14 days of intervention, tissue histopathology, flow cytometry, ELISA, qPCR, metabolomics, and Western blot analysis were conducted. The findings revealed a significant mitigation of lung tissue damage scores (P < 0.001) and collagen deposition (P < 0.001) following CDP treatment. CDP concomitantly enhanced key pulmonary functional parameters, including the lung wet/dry ratio, oxygenation index, and arterial partial pressure of carbon dioxide (PaCO2) (P < 0.001). CDP treatment demonstrated dose-dependent increases in regulatory T cell (Treg) frequencies (P < 0.001), accompanied by significant suppression of T helper 17 (Th17) cell populations (P < 0.001). These immunomodulatory effects correlated with decreased levels of pro-inflammatory mediators, including TNF-α, IL-6, IL-17, and IL-22 (P < 0.001). Furthermore, CDP corrected arginine-polyamine metabolic dysregulation by decreasing arginine, putrescine, and spermidine levels (P < 0.001), while increasing spermine levels and the spermidine/spermine ratio (P < 0.001). CDP enhanced phosphorylation of signal transducer and activator of transcription 5 (STAT5), thereby upregulating the p-STAT5/STAT5 signaling axis (P < 0.001), while concurrently suppressing the p-STAT3/STAT3 pathway (P < 0.001). CDP may modulate immune balance by synergistically regulating arginine metabolism and STAT signaling pathways, offering a potential multi-target therapeutic strategy for bronchiectasis.
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