Abstract
Objective The study aims to research the interventional effect and mechanism of astragaloside IV (Ast) synergizing with ferulic acid (FA) on idiopathic pulmonary fibrosis (IPF) induced by bleomycin in mice. Methods The mice were randomly divided into seven groups with 10 mice in each group, namely, a sham operation group, a model group, a miRNA-29b (miR-29) group, a miR-29b negative control group (NC group), a FA group, an Ast group, and a combination group. A mouse model of pulmonary fibrosis was established by intratracheal instillation of bleomycin. Samples were collected after 28 days of continuous administration. Hematoxylin and eosin (HE) and Masson staining were used to observe pathological changes in the lung tissue, and the degree of fibrosis was evaluated using the hydroxyproline content. Changes in transforming growth factor-β1 (TGF-β1) and Smad3 in the lung were observed using immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) in the serum. PCR was used to detect the expression of the miR-29b, TGF-β1, Smad3, and nuclear factor E2-related factor 2 (Nrf2) genes. Western blotting was used to detect the content of the TGF-β/Smad3 protein. Results Ferulic acid combined with astragaloside IV reduced the degree of pulmonary fibrosis and the synthesis of hydroxyproline in lung tissue. The combination of the two also regulated the oxidative stress response ， TGF-β1/Smad3 pathway and miR-29b in lung tissue. Conclusion Astragaloside IV combined with ferulic acid regulated the oxidative stress of lung tissues and TGF-β1/Smad3 signaling through miR-29b, thereby reducing the degree of pulmonary fibrosis. This provides a reference direction for the clinical treatment of IPF patients.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a disease of unknown origin with progressive and diffuse pulmonary fibrosis accompanied by honeycomb cyst-like changes.e median survival time of patients is only two to three years, and the mortality rate is nearly the same as that of malignant tumors [1]
Ferulic acid inhibits the secretion of activated TGF-β 1 [11, 12]. e cooperation of ferulic acid and astragaloside IV can inhibit fibrosis by regulating the nuclear factor E2-related factor 2 (Nrf2) and transforming growth factor-β1 (TGF-β1)/Smad3 pathways [13]. ey maintain a synergistic antifibrosis effect in rats with obstructive nephropathy [14]. ere is evidence from clinical practice and experimental research that a Chinese herbal medicine mixture has an enhanced curative effect than a single drug, and the combination of astragaloside IV (Ast) and ferulic acid (FA) may have a synergistic effect [15, 16]. e purpose of the study is to explore the therapeutic effects of astragaloside IV and ferulic acid on pulmonary fibrosis and their synergistic mechanism
C57BL male mice weighing 22 to 24 g were bought from Beijing Vital River Labomouseory Animal Technology Co., Ltd. (Beijing, China). e mice were housed under laboratory conditions . e temperature was kept at 22–26°C, and the ambient humidity was kept at 50–60%. e food and water were free to mice
Summary
Idiopathic pulmonary fibrosis (IPF) is a disease of unknown origin with progressive and diffuse pulmonary fibrosis accompanied by honeycomb cyst-like changes. MiR-29 in lung tissue is related to oxidative stress, the expression of the transforming growth factor-β1(TGF-β1)/Smad signal transduction pathway. Oxidative stress induced by malondialdehyde (MDA) and superoxide dismutase (SOD) can activate TGF-β1/Smad signal transduction and participate in the occurrence of fibrosis. Oxidative stress and the TGF-β1/Smad signal interact with other processes and rapidly promote IPF. Modern pharmacological studies have demonstrated [8] that astragaloside IV (Ast) and ferulic acid (FA) are the effective components of the Danggui Buxue Decoction that inhibit fibrosis. E cooperation of ferulic acid and astragaloside IV can inhibit fibrosis by regulating the nuclear factor E2-related factor 2 (Nrf2) and TGF-β1/Smad pathways [13]. E purpose of the study is to explore the therapeutic effects of astragaloside IV and ferulic acid on pulmonary fibrosis and their synergistic mechanism Ferulic acid inhibits the secretion of activated TGF-β 1 [11, 12]. e cooperation of ferulic acid and astragaloside IV can inhibit fibrosis by regulating the nuclear factor E2-related factor 2 (Nrf2) and TGF-β1/Smad pathways [13]. ey maintain a synergistic antifibrosis effect in rats with obstructive nephropathy [14]. ere is evidence from clinical practice and experimental research that a Chinese herbal medicine mixture has an enhanced curative effect than a single drug, and the combination of astragaloside IV (Ast) and ferulic acid (FA) may have a synergistic effect [15, 16]. e purpose of the study is to explore the therapeutic effects of astragaloside IV and ferulic acid on pulmonary fibrosis and their synergistic mechanism
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