Mechanism of Sorbus tianschanica in regulating asthmatic airway inflammation through TLR4/PI3K/Akt/MMP9 signaling pathway.
10.19540/j.cnki.cjcmm.20250508.401
- Author:
Wen-Kai WANG
1
;
Jun-Min CHANG
2
;
Xiao-Li MA
1
;
Gai-Ru LI
1
Author Information
1. College of Pharmacy, Xinjiang Medical University Urumqi 830011, China.
2. College of Pharmacy, Xinjiang Medical University Urumqi 830011, China Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology Urumqi 830000, China.
- Publication Type:Journal Article
- Keywords:
Sorbus tianschanica;
TLR4/PI3K/Akt/MMP9 signaling pathway;
airway inflammation;
asthma;
molecular docking
- MeSH:
Animals;
Asthma/metabolism*;
Toll-Like Receptor 4/metabolism*;
Signal Transduction/drug effects*;
Mice;
Phosphatidylinositol 3-Kinases/metabolism*;
Proto-Oncogene Proteins c-akt/metabolism*;
Matrix Metalloproteinase 9/metabolism*;
Mice, Inbred BALB C;
Drugs, Chinese Herbal/administration & dosage*;
Female;
Humans;
Lung/immunology*;
Male
- From:
China Journal of Chinese Materia Medica
2025;50(15):4304-4314
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the effects and mechanisms of the water extract from Sorbus tianschanica(STE) on asthmatic airway inflammation, the mice were randomly divided into six groups, including a control group, a model group, a positive drug dexamethasone group(2 mg·kg~(-1)), a low-dose STE group(1 g·kg~(-1)), a medium-dose STE group(2 g·kg~(-1)), and a high-dose STE group(4 g·kg~(-1)). Except for the control group, all groups were subjected to ovalbumin induction to establish an asthma mouse model. The anti-inflammatory effects of STE were evaluated by examining pathological changes in lung tissue and measuring the levels of interleukin(IL)-4 and IL-5 in bronchoalveolar lavage fluid(BALF). Transcriptomic and proteomic methods were further employed to analyze differentially expressed genes and proteins, as well as their associated signaling pathways in lung tissue. Subsequently, the expression changes of key genes were verified by reverse transcription-quantitative polymerase chain reaction(RT-qPCR), and immunohistochemistry and Western blot methods were used to explore the regulatory mechanisms of STE in the pathogenesis of asthma in mice. Molecular docking was performed by using AutoDock Vina software to evaluate the binding affinity of the main active components in STE with the target proteins, including phosphatidylinositol-3-kinase catalytic subunit α(PIK3CA), Toll-like receptor 4(TLR4), protein kinase B1(Akt1), and matrix metallopeptidase 9(MMP9). The results showed significant inflammatory cell infiltration and fibrous tissue proliferation in the lung tissue of mice in the model group. However, these pathological changes were markedly reduced following STE intervention. Compared with those of the control group, the expression levels of IL-4 and IL-5 in the BALF of the model group were significantly increased but notably decreased following STE intervention. Transcriptomic and proteomic analyses identified key genes and proteins associated with allergic asthma, including tumor necrosis factor(TNF), IL-6, TLR4, PIK3CA, and MMP9. RT-qPCR validation revealed that high-dose STE intervention significantly downregulated the expressions of PIK3CA, IL-6, Akt1, MMP9, IL-13, nuclear factor-kappa B(NF-κB), TNF, CXC motif chemokine ligand 1(CXCL1), and TLR4 mRNAs and significantly upregulated the expression of signal transducer and activator of transcription 1(STAT1) mRNA. Western blot and immunohistochemical analyses confirmed that STE significantly downregulated the expressions of MMP9, TLR4, PIK3CA, and phosphorylated protein kinase B(p-Akt) in lung tissue of asthmatic mice. Moreover, molecular docking demonstrated that kaempferol-3,7-diglucoside, isoquercitrin, quercetin-3-gentiobioside, and hyperoside in STE exhibited stable binding affinities with PIK3CA, TLR4, Akt1, and MMP9, suggesting that the active components may exert anti-inflammatory effects by targeting and modulating asthma-related signaling pathways. In summary, STE exerts anti-asthmatic effects by inhibiting the expressions of PIK3CA, MMP9, p-Akt, and TLR4 and regulating the TLR4/PI3K/Akt/MMP9 signaling pathway.
