Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (1): 138-148.DOI: 10.19852/j.cnki.jtcm.2026.01.013
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A network pharmacology-based strategy to discover the molecular mechanism of correlation between the treatment of bronchial asthma with Wenyang Huayin decoction (温阳化饮方) and autophagy
ZHAO Mingzhe1, YAN Peizheng2,3,4, ZHAO Xiaomin5, CHEN Yufan1, LI Mengsitong1, ZHOU Yuping6, ZHANG Lu7, DOU Liwen1, LIU Yan1, ZHENG Hong1(
), LI Jia1()
- 1 School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
2 Institute of Traditional Chinese Medicine Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
3 High Level Key Disciplines of Traditional Chinese Medicine Basic Theory of Traditional Chinese Medicine, National Administration of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
4 Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
5 Department of Traditional Chinese Medicine, Shandong College of Traditional Chinese Medicine, Yantai 264199, China
6 Hospital of Shandong Technology and Business University, Yantai 264005, China
7 School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
-
Received:2024-05-12Online:2026-02-15Published:2026-01-28 -
Contact:ZHENG Hong, School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.zhads@163.com ; Li Jia, School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.ljytl7172@163.com ;Telephone: +86-13001700701; +86-15154188997 -
About author:ZHAO Mingzhe andYAN Peizheng are co-first authors and contributed equally to this work -
Supported by:National Natural Science Foundation of China: Study on the Mechanism of Airway Inflammation in Rats with Bronchial Asthma Cold Drink Lung Syndrome Treated with Metastasis Associated Lung Adenocarcinoma Transcript 1 Regulated Autophagy(82004233);Shandong Province Traditional Chinese Medicine Science and Technology Project: Exploring the Mechanism of Xiaoqinglong Tang's Intervention in Bronchial Asthma Cold Drink Lung Syndrome through the "Temperature Sensing Channel Transient Receptor Potential Mitochondrial Autophagy" Pathway based on Transcriptomics Combined with Proteomics(MR20241737);Shandong Province Traditional Chinese Medicine Science and Technology Project: Optimization of Ultrasonic Extraction Process and Study on Structure and Activity of Asarum Polysaccharides(Q-2023042);Shandong Province Traditional Chinese Medicine Science and Technology Project: Study on the Mechanism of Ma Gui Synergistic Intervention on Airway Inflammatory Response in Rats with Asthma Cold Drink and Lung Accumulation Syndrome(Q-2023122);2023 Qilu Biancang Traditional Chinese Medicine Talent Cultivation Project, Shandong Province Medical and Health Science and Technology Development Plan Project: Study on the Mechanism of Airway Epithelial Cell Inflammation Induced by Cellular Autophagy Regulation lncRNA Metastasis Associated Lung Adenocarcinoma Transcript 1 Antagonism Against Ovalbumin Intervention(202203020866)
Cite this article
ZHAO Mingzhe, YAN Peizheng, ZHAO Xiaomin, CHEN Yufan, LI Mengsitong, ZHOU Yuping, ZHANG Lu, DOU Liwen, LIU Yan, ZHENG Hong, LI Jia. A network pharmacology-based strategy to discover the molecular mechanism of correlation between the treatment of bronchial asthma with Wenyang Huayin decoction (温阳化饮方) and autophagy[J]. Journal of Traditional Chinese Medicine, 2026, 46(1): 138-148.
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Figure 1 PPI network analysis and KEGG pathway enrichment analysis A: PPI network of the core targets, the core key targets include TNF, CXCL8, HRAS, MMP9, MAPK14, CASP8, IL1B, SIRT1, PIK3, CCR7, LYN, and PTK2; B: the enrichment pathways obtained using KEGG sequencing mainly included the TGF-β signaling pathway, mTOR signaling pathway, TNF signaling pathway, and PI3K-AKT signaling pathway. mammalian target of rapamycin, transforming growth factor-β. PPI: protein interaction; KEGG: Kyoto encyclopedia of genes and genomes; TNF: tumor necrosis factor; CXCL8: C-X-C motif chemokine ligand 8; HRAS: Harvey rat sarcoma virus oncogene; MMP9: matrix metalloproteinase 9; MAPK14: mitogen-activated protein kinase 14; CASP8: caspase 8; IL1B: interleukin 1 beta; SIRT1: sirtuin 1; PIK3: phosphoinositide 3-kinase; CCR7: C-C motif chemokine receptor type 7; LYN: LYN kinase; PTK2: protein tyrosine kinase 2.
Figure 1 PPI network analysis and KEGG pathway enrichment analysis A: PPI network of the core targets, the core key targets include TNF, CXCL8, HRAS, MMP9, MAPK14, CASP8, IL1B, SIRT1, PIK3, CCR7, LYN, and PTK2; B: the enrichment pathways obtained using KEGG sequencing mainly included the TGF-β signaling pathway, mTOR signaling pathway, TNF signaling pathway, and PI3K-AKT signaling pathway. mammalian target of rapamycin, transforming growth factor-β. PPI: protein interaction; KEGG: Kyoto encyclopedia of genes and genomes; TNF: tumor necrosis factor; CXCL8: C-X-C motif chemokine ligand 8; HRAS: Harvey rat sarcoma virus oncogene; MMP9: matrix metalloproteinase 9; MAPK14: mitogen-activated protein kinase 14; CASP8: caspase 8; IL1B: interleukin 1 beta; SIRT1: sirtuin 1; PIK3: phosphoinositide 3-kinase; CCR7: C-C motif chemokine receptor type 7; LYN: LYN kinase; PTK2: protein tyrosine kinase 2.
Figure 2 Changes in pulmonary function and pathology in experimental rats A: pre-experimental lung function tests in rats: Ri, Re, Cldyn; B: post-experimental lung function parameters Ri, Re, and Cldyn in rats; C: HE-stained histopathology of rat lung tissue, scale bar = 50 μm. A1, B1: Ri; A2, B2: Re; A3, B3: Cldyn; C1: HE-stained lung tissue sections from control rats; C2: HE-stained histological sections of rat lung tissue from the model group; C3: HE-stained lung tissue sections from WYHYD group rats. Control group: no drug, no stress; Model group: OVA group (Model group were sensitized via intraperitoneal injection of 1 mL antigen containing 100 mg of ovalbumin + 100 mg of aluminum hydroxide per mL on the first and eighth days. On the 15th day, asthma was induced in the rats with 1% ovalbumin atomized using an ultrasonic nebulizer once daily for 30 min each time for 8 d); WYHYD: WYHYD group (1.6 mL/100 g each time, Crude drug and body weight: 9.8214 g·kg?1·d?1, the dosing period is from days 2 to 22 of the experiment). WYHYD: Wenyang Huayin decoction; HE: hematoxylin-eosin staining; Ri: inspiratory resistance; Re: expiratory resistance; Cldyn: pulmonary ventilation compliance; OVA: ovalbumin. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 6). aP < 0.01, compared with the control group; bP < 0.01, compared with the model group.
Figure 2 Changes in pulmonary function and pathology in experimental rats A: pre-experimental lung function tests in rats: Ri, Re, Cldyn; B: post-experimental lung function parameters Ri, Re, and Cldyn in rats; C: HE-stained histopathology of rat lung tissue, scale bar = 50 μm. A1, B1: Ri; A2, B2: Re; A3, B3: Cldyn; C1: HE-stained lung tissue sections from control rats; C2: HE-stained histological sections of rat lung tissue from the model group; C3: HE-stained lung tissue sections from WYHYD group rats. Control group: no drug, no stress; Model group: OVA group (Model group were sensitized via intraperitoneal injection of 1 mL antigen containing 100 mg of ovalbumin + 100 mg of aluminum hydroxide per mL on the first and eighth days. On the 15th day, asthma was induced in the rats with 1% ovalbumin atomized using an ultrasonic nebulizer once daily for 30 min each time for 8 d); WYHYD: WYHYD group (1.6 mL/100 g each time, Crude drug and body weight: 9.8214 g·kg?1·d?1, the dosing period is from days 2 to 22 of the experiment). WYHYD: Wenyang Huayin decoction; HE: hematoxylin-eosin staining; Ri: inspiratory resistance; Re: expiratory resistance; Cldyn: pulmonary ventilation compliance; OVA: ovalbumin. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 6). aP < 0.01, compared with the control group; bP < 0.01, compared with the model group.
Figure 3 Serum inflammatory cytokine levels and relative expression of Atg gene mRNA in lung tissue A: levels of inflammatory cytokines TNF-α and TGF-β in rat serum; A1: TGF-β; A2: TNF-α; B: relative expression levels of Atg3, 5, 7, and 12 mRNA in rat lungs; B1: Atg3; B2: Atg5; B3: Atg7; B4: Atg12. Control group: no drug, no stress; Model group: OVA group (Model group were sensitized via intraperitoneal injection of 1 mL antigen containing 100 mg of ovalbumin +100 mg of aluminum hydroxide per mL on the first and eighth days. On the 15th day, asthma was induced in the rats with 1% ovalbumin atomized using an ultrasonic nebulizer once daily for 30 min each time for 8 d); WYHYD: WYHYD group (1.6 mL/100 g each time, Crude drug and body weight: 9.8214 g·kg?1·d?1, the dosing period is from days 2 to 22 of the experiment). WYHYD: Wenyang Huayin decoction; TNF-α: tumour necrosis factor-alpha; TGF-β: transforming growth factor-β; Atg 3, 5, 7, 12: autophagy related 3, 5, 7, 12. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 6). aP < 0.01, compared with the control group; bP < 0.01, compared with the model group.
Figure 3 Serum inflammatory cytokine levels and relative expression of Atg gene mRNA in lung tissue A: levels of inflammatory cytokines TNF-α and TGF-β in rat serum; A1: TGF-β; A2: TNF-α; B: relative expression levels of Atg3, 5, 7, and 12 mRNA in rat lungs; B1: Atg3; B2: Atg5; B3: Atg7; B4: Atg12. Control group: no drug, no stress; Model group: OVA group (Model group were sensitized via intraperitoneal injection of 1 mL antigen containing 100 mg of ovalbumin +100 mg of aluminum hydroxide per mL on the first and eighth days. On the 15th day, asthma was induced in the rats with 1% ovalbumin atomized using an ultrasonic nebulizer once daily for 30 min each time for 8 d); WYHYD: WYHYD group (1.6 mL/100 g each time, Crude drug and body weight: 9.8214 g·kg?1·d?1, the dosing period is from days 2 to 22 of the experiment). WYHYD: Wenyang Huayin decoction; TNF-α: tumour necrosis factor-alpha; TGF-β: transforming growth factor-β; Atg 3, 5, 7, 12: autophagy related 3, 5, 7, 12. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 6). aP < 0.01, compared with the control group; bP < 0.01, compared with the model group.
Figure 4 Autophagy-related protein expression was observed using Western blot combined with the measured experimental data A: chemical development image of protein bands; B: analysis of relative expression levels of AKT phosphorylation; C: analysis of relative expression levels of PI3K phosphorylation; D: analysis of relative expression levels of mTOR phosphorylation. Control group: no drug, no stress; Model group: OVA group (Model group were sensitized via intraperitoneal injection of 1 mL antigen containing 100 mg of ovalbumin + 100 mg of aluminum hydroxide per mL on the first and eighth days. On the 15th day, asthma was induced in the rats with 1% ovalbumin atomized using an ultrasonic nebulizer once daily for 30 min each time for 8 d); WYHYD: WYHYD group (1.6 mL/100 g each time, Crude drug and body weight: 9.8214 g·kg?1·d?1, the dosing period is from days 2 to 22 of the experiment). WYHYD: Wenyang Huayin decoction; AKT: protein kinase B; p-AKT: phosphorylated AKT; PI3K: phosphatidylinositol 3-kinase; p-PI3K: phosphorylated PI3K; mTOR: mechanistic target of rapamycin; p-mTOR: phosphorylated mTOR. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 3). aP < 0.01, compared with the control group; bP < 0.01, compared with the model group.
Figure 4 Autophagy-related protein expression was observed using Western blot combined with the measured experimental data A: chemical development image of protein bands; B: analysis of relative expression levels of AKT phosphorylation; C: analysis of relative expression levels of PI3K phosphorylation; D: analysis of relative expression levels of mTOR phosphorylation. Control group: no drug, no stress; Model group: OVA group (Model group were sensitized via intraperitoneal injection of 1 mL antigen containing 100 mg of ovalbumin + 100 mg of aluminum hydroxide per mL on the first and eighth days. On the 15th day, asthma was induced in the rats with 1% ovalbumin atomized using an ultrasonic nebulizer once daily for 30 min each time for 8 d); WYHYD: WYHYD group (1.6 mL/100 g each time, Crude drug and body weight: 9.8214 g·kg?1·d?1, the dosing period is from days 2 to 22 of the experiment). WYHYD: Wenyang Huayin decoction; AKT: protein kinase B; p-AKT: phosphorylated AKT; PI3K: phosphatidylinositol 3-kinase; p-PI3K: phosphorylated PI3K; mTOR: mechanistic target of rapamycin; p-mTOR: phosphorylated mTOR. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 3). aP < 0.01, compared with the control group; bP < 0.01, compared with the model group.
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