Mechanism study of Processed Pinellia ternata alleviating COPD injury through macrophages and fibroblasts Crosstalk

doi:10.12092/j.issn.1009-2501.2026.05.002

Abstract

Abstract:

AIM: To explore the mechanism of Processed Pinellia ternata in treating chronic obstructive pulmonary disease (COPD). METHODS: Forty male C57BL/6J mice were randomly divided into control group (n=8), model group (n=12), Processed Pinellia ternata group (1.5 g/kg, n=12), and aminophylline group (1 mg/kg, n=8). COPD model was established using smoke inhalation combined with lipopolysaccharide nasal drops. HE staining was employed to observe pathological damage in lung tissue. Lung tissue fibrosis was detected by Masson, MMP2, and MMP9 staining. Fibroblast transformation was tested α-SMA staining. CD206 and F4/80 staining were used to evaluated M2 macrophages polarization. The expression of TGF-β1 and Arg-1 genes were checked though qPCR, the level of Stat1 and p-Stat1 proteins were measured by Western blotting. In addition, macrophages and fibroblasts were co-cultured by transwell chambers, the (cells) were divided into blank control group, normal control group, model group, and low-, medium-, high-dose Pinellia ternata group groups (10, 20, 40 μg/mL, respectively), the fibroblasts transformation was detected by α-SMA staining. RESULTS: Processed Pinellia ternata can significantly alleviate COPD injury (P<0.01), inhibit lung tissue proliferation and fibrosis (P<0.001), reduce the relative expression levels of TGF-β1 and Arg-1 genes (P<0.05), inhibit fibroblast transformation (P<0.05), reduce M2 macrophage polarization (P<0.05) and increase the p-Stat1/Stat1 ratio (P<0.05). CONCLUSION: Processed Pinellia ternata improves the fibrosis process in COPD by macrophages and fibroblasts crosstalk blocking, which may be related to suppressed M2 macrophage polarization and activated the Stat1 pathway.

Key words: Processed Pinellia ternata, chronic obstructive pulmonary disease (COPD), fibrosis, Crosstalk

CLC Number:

R965.2

Zongfeng WEI, Jinlong TAN, Menghan SUN, Nailiang ZHU, Yingying ZHAI, Qiong CHEN, Jingjing BI, Lixiang LIANG, Min SONG. Mechanism study of Processed Pinellia ternata alleviating COPD injury through macrophages and fibroblasts Crosstalk[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(5): 585-595.

Figures/Tables 10

Table 1 Primer sequences

Gene	Forward primer	Reward primer
TGF-β1	ACTGGAGTTGTACGGCAGTG	GGGGCTGATCCCGTTGATTT
Arg-1	AGCACTGAGGAAAGCTGGTC	TACGTCTCGCAAGCCAATGT
GAPDH	ACAGCAACAGGGTGGTGGAC	TTTGAGGGTGCAGCGAACTT

Fig.1 The effect of Processed Pinellia ternata on COPD ($\bar x $±s, n≥8) A: lung tissues photos in groups; B: lung/body weight ratio analysis. ***P<0.001, compared with control group; ##P<0.01, compared with model group.

Fig.2 The effect of Processed Pinellia ternata on lung tissue injury ($\bar x $±s, n=3) A: HE staining of alveoli in each group; B: HE staining of bronchi in each group; C-F: statistical analysis of WT%, WA%, smooth muscle thickness and bronchial wall thickness. ****P<0.001, compared with control group; ###P<0.001, compared with model group.

Fig.3 The effect of Processed Pinellia ternata on pulmonary fibrosis ($\bar x $±s, n=3) A-B: Alveolar Masson staining and fibrosis analysis in each group; C-D: Bronchi Masson staining and fibrosis analysis in each group; ***P<0.001, compared with control group; ###P<0.001, compared with model group.

Fig.4 The effect of Processed Pinellia ternata on the expression of MMP2 and MMP9 ($\bar x $±s, n=3) A-D: Immunohistochemical staining and quantitative analysis of MMP2 in the alveoli and bronchi of lung tissue; E-H: Immunohistochemical staining and quantitative analysis in the alveoli and bronchi of lung tissue; ***P<0.001, compared with control group; ###P<0.001, compared with model group.

Fig.5 The effect of Processed Pinellia ternata on fibroblast transformation in COPD model ($\bar x $±s, n=3) A-B: α-SMA immunohistochemical staining and quantitative analysis of alveolar in each group; C-D: α-SMA immunohistochemical staining and quantitative analysis of bronchi in each group; **P<0.01, compared with control group; #P<0.05, ##P<0.01, compared with model group.

Fig.6 Effect of Processed Pinellia ternata on fibroblast transformation in co-culture model ($\bar x $±s, n=3) A: Co-culure model establishment; B-C: α-SMA immunofluorescence staining and quantitative analysis of each group; ***P<0.001, compared with control group; ###P<0.001, compared with model group.

Fig.7 The effect of Processed Pinellia ternata on the expression of TGF-β1 and Arg-1 ($\bar x $±s, n=3) A-B: TGF-β1 and Arg-1 genes expression and quantitative analysis in the lung tissues. *P<0.05, ***P<0.001, compared with control group; #P<0.05, ##P<0.01, compared with model group.

Fig.8 The effect of Processed Pinellia ternata on M2 macrophages polarization ($\bar x $±s, n=3) A: F4/80 immunohistochemical staining in lung tissue; B: CD206 immunohistochemical staining in lung tissue; C: Quantitative analysis of CD206/F4/80 ratio. **P<0.01, compared with control group; #P<0.05, compared with model group.

Fig.9 The effect of Processed Pinellia ternata on the Stat1 signaling pathway ($\bar x $±s, n=3) A-B: expression levels and quantitative analysis of p-Stat1, Stat1 and β-actin in lung tissues. *P<0.05, compared with control group; #P<0.05, compared with model group.

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