Related Experiment Video
Updated: Apr 7, 2026
Assessment of Respiratory Function in Conscious Mice by Double-chamber Plethysmography
Published on: July 10, 2018
Polydatin Relieves Airway Remodeling by Inhibiting P2X7R-NLRP3-Mediated Excessive Autophagy in Asthma
Guangxing Li1,2, Liangchang Li1,2, Zhiguang Wang1,3
1Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, Jilin, China.
Background:
Asthma is characterized by chronic airway inflammation and remodeling. Polydatin (PD), a natural compound, has shown anti-inflammatory potential, but its role in asthma-related airway remodeling and the underlying mechanisms involving the P2X7R-NLRP3 inflammasome axis and autophagy remain unclear.
Methods:
An ovalbumin-induced asthmatic mouse model and primary airway smooth muscle cells (ASMCs) were used. Mice were treated with PD or the P2X7R agonist BzATP. Assessments included airway hyperresponsiveness, histopathology, inflammatory cell counts, cytokine profiling (ELISA), flow cytometry for T-cell subsets, and protein analysis via western blot and immunofluorescence. Autophagy was evaluated by measuring LC3-I/II, Beclin-1, and acidic vesicular organelles. Key signaling molecules (P2X7R, NLRP3, ASC, caspase-1, LKB1/AMPK/mTOR) were analyzed. In vitro, ASMCs were treated with BzATP, PD, and specific inhibitors; P2X7R was silenced using siRNA.
Results:
PD treatment significantly alleviated ovalbumin-induced airway hyperresponsiveness, inflammatory cell infiltration, goblet cell hyperplasia, and collagen deposition in mice. It restored the Th1/Th2 and Th17/Treg balance and reduced levels of airway remodeling markers (α-SMA, PCNA, VEGF, MMP-9). PD suppressed excessive autophagy (reduced LC3-I/II and Beclin-1) and modulated the LKB1/AMPK/mTOR pathway. Furthermore, PD inhibited the ATP/P2X7R axis, leading to reduced NLRP3 inflammasome activation, caspase-1 activity, and secretion of IL-1β and IL-18. In ASMCs, PD reversed BzATP-induced autophagy and NLRP3 activation. Silencing P2X7R enhanced AMPK phosphorylation, underscoring its role in the pathway.
Conclusion:
PD attenuates airway remodeling in asthma by inhibiting the ATP/P2X7R-NLRP3 inflammasome axis and subsequent excessive autophagy, partly through modulation of the LKB1/AMPK/mTOR signaling pathway. These findings highlight PD as a promising therapeutic candidate for asthma treatment.
Related Concept Videos
01:26Asthma-II: Pathophysiology and Classification
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
01:24Antiasthma Drugs: Methylxanthines
Theophylline is thought to inhibit phosphodiesterase enzymes, increasing intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). This rise in cAMP and cGMP concentrations stimulates cardiac function,...
01:25Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
01:20Asthma: Pathogenesis and Management
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.
01:19Antiasthma Drugs: Leukotriene Modifiers
Leukotriene modifiers work through two distinct mechanisms:
01:20Antiasthma Drugs: Muscarinic Receptor Antagonists
Antimuscarinic agents compete with ACh for the same binding site on the muscarinic receptors. By binding to these receptors, they inhibit the downstream effects of ACh and block the parasympathetic...