Effect of supercritical carbon dioxide fluid extract from Chrysanthemum indicum Linne on bleomycin-induced pulmonary fibrosis.

ABSTRACT:

Background

As a prevalent type of cryptogenic fibrotic disease with high mortality, idiopathic pulmonary fibrosis (IPF) still lacks effective therapeutic drugs. The compounds extracted from buds and flowers of Chrysanthemum indicum Linné with supercritical-carbon dioxide fluid (CI_SCFE) has been confirmed to have antioxidant, anti-inflammatory, and lung-protective effects. This paper aimed to clarify whether CI_SCFE could treat IPF induced by bleomycin (BLM) and elucidate the related mechanisms.

Methods

Rats (Sprague-Dawley, male) were separated into the following groups: normal, model, pirfenidone (50 mg/kg), CI_SCFE-L, -M, and -H (240, 360, and 480 mg/kg/d, i.g., respectively, for 4 weeks). Rats were given BLM (5 mg/kg) via intratracheal installation to establish the IPF model. A549 and MRC-5 cells were stimulated by Wnt-1 to establish a cell model and then treated with CI_SCFE. Haematoxylin-eosin (H&E) and Masson staining were employed to observe lesions in the lung tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) were performed to observe changes in genes and proteins connected with the Wnt/β-catenin pathway.

Results

CI_SCFE inhibited the proliferation of MRC-5 cells (IC₅₀: 2.723 ± 0.488 μg/mL) and A549 cells (IC₅₀: 2.235 ± 0.229 μg/mL). In rats, A549 cells, and MRC-5 cells, BLM and Wnt-1 obviously induced the protein expression of α-smooth muscle actin (α-SMA), vimentin, type I collagen (collagen-I), and Nu-β-catenin. The mRNA levels of matrix metalloproteinase-3 (MMP-3) and - 9 (MMP-9), two enzymes that degrade and reshape the extracellular matrix (ECM) were also increased while those of tissue inhibitor of metalloproteinase 1 (TIMP-1) were decreased. However, CI_SCFE reversed the effects of BLM and Wnt-1 on the expression pattern of these proteins and genes.

Conclusion

These findings showed that CI_SCFE could inhibit IPF development by activating the Wnt/β-catenin pathway and may serve as a treatment for IPF after further investigation.

SUBMITTER: Nie J 

PROVIDER: S-EPMC8464116 | biostudies-literature |

REPOSITORIES: biostudies-literature