Journal Article Epublish
PubMed: 40538533 DOI: 10.3389/fphar.2025.1573525
Polydatin-curcumin formulation alleviates CTD-ILD-like lung injury in mice via GABBR/PI3K/AKT/TGF-β pathway.
Front Pharmacol 16:1573525
Authors: Zhengju Zhang, Yao Zhang, Qingyi Lu, Yanan Wang, Guodong Li, Guoju Jin, Weiguo Ma, Yuyue Liu, Lei Yang, Hui Liu, Honghong Zhang, Wen Gu, Xinqi Deng, Chunguo Wang, Fengxian Meng
Affiliations
- Beijing University of Chinese Medicine, Beijing, China.
- Capital Medical University, Beijing, China.
- Changping District Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, China.
- Shunyi Hospital, Beijing Traditional Chinese Medicine Hospital, Beijing, China.
- Institute Of Chinese Materia Medica China Academy of Chinese Medical Sciences, Beijing, China.
Abstract
Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a systemic autoimmune disease with high morbidity and hazard, characterized by progressive pulmonary inflammation and fibrosis. The monomer formulation of polydatin and curcumin (PD + Cur) for lung injury in CTD-ILD was optimized from Curcumae Longae Rhizoma (Curcuma Longa L.) and Polygoni Cuspidati Rhizoma Et Radix (Polygonum cuspidatum Sieb. et Zucc.). Mice with CTD-ILD-like lung injury were established by a single intratracheal drip of bleomycin. After intervening in model mice for 4 weeks, PD + Cur attenuated alveolar atrophy, fibrillar collagen formation, and thickened alveolar septa in the lung, improved serum biomarkers TOLLIP, MUC5B, KL-6, SP-D, and RCN3, and suppressed serum immunoinflammatory factors IL-6, CCL-18, and SF. The transcriptome sequencing showed that PD + Cur ameliorated CTD-ILD mainly by regulating aberrant immunoinflammation, which was further confirmed by proteomics that the PI3K/AKT/TGF-β pathway was a key pathway. Further, PD + Cur was found to affect amino acid metabolism in the serum significantly. The B-type receptor for GABA (GABBR) agonist baclofen was further found to attenuate CTD-ILD-like lung injury and modulate PI3K/AKT/TGF-β signaling. However, the inhibition of AKT, transforming growth factor beta receptor type 3 (TGFβR3), a key indicator downstream of PI3-kinase subunit p85-alpha (PI3KR1), by PD + Cur was reversed after intervention with the GABBR receptor inhibitor CGP52432. PD + Cur has an ameliorative effect on CTD-ILD-like lung injury by targeting GABBR to modulate the PI3K/AKT/TGF-β pathway.
MeSH
Lung, Serum, Lung Injury, Curcumin