Cistanche deserticola polysaccharide alleviates bronchiectasis by regulating arginine metabolism and STAT signaling pathway.

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.