ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Ethnopharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1573525

This article is part of the Research TopicApplications of Medicinal Plants and Their Metabolites in Fibrotic Disease: Novel Strategies, Mechanisms, and Their Impact on Clinical PracticeView all 6 articles

Polydatin-Curcumin Formulation Alleviates CTD-ILD-like Lung Injury in Mice via GABBR/PI3K/AKT/TGF-β Pathway

Provisionally accepted
Zhengju ZhangZhengju Zhang1Yao ZhangYao Zhang1Qingyi LuQingyi Lu1Yanan WangYanan Wang2Guodong LiGuodong Li3Guoju JinGuoju Jin1Weiguo MaWeiguo Ma1Yuyue LiuYuyue Liu1Lei YangLei Yang1Hui LiuHui Liu1Honghong ZhangHonghong Zhang4Wen GuWen Gu2XINQI DENGXINQI DENG5*Chunguo WangChunguo Wang1*Fengxian MengFengxian Meng1*
  • 1Beijing University of Chinese Medicine, Beijing, China
  • 2Capital Medical University, Beijing, Beijing Municipality, China
  • 3Changping District Hospital of Integrated traditional Chinese and Western Medicine, Beijing, China
  • 4Shunyi Hospital, Beijing Traditional Chinese Medicine Hospital, Beijing, China
  • 5Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, Beijing Municipality, China

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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.

Keywords: CTD-ILD, Polydatin, Curcumin, GABBR, PI3K/AKT/TGF-β

Received: 09 Feb 2025; Accepted: 21 May 2025.

Copyright: © 2025 Zhang, Zhang, Lu, Wang, Li, Jin, Ma, Liu, Yang, Liu, Zhang, Gu, DENG, Wang and Meng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
XINQI DENG, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, Beijing Municipality, China
Chunguo Wang, Beijing University of Chinese Medicine, Beijing, China
Fengxian Meng, Beijing University of Chinese Medicine, Beijing, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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