Chelerythrine Ameliorates Pulmonary Fibrosis via Activating the Nrf2/ARE Signaling Pathway. 2021

Ling Peng, and Li Wen, and Qingfeng Shi, and Feng Gao, and Bin Huang, and Changming Wang
Department of Nephrology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.

Chelerythrine (CHE) is a natural benzophenanthridine alkaloid, which has shown its anti-fibrosis activity in kidney and liver, while the impact of CHE in pulmonary fibrosis is still unclear. This study is developed to explore the impact and mechanism of CHE in pulmonary fibrosis. Pulmonary fibrosis mouse models were established through intratracheal injection of bleomycin (BLM), after which the mice were intraperitoneally injected with CHE (0.375 or 0.75 mg/kg/d) every other day. The mice were sacrificed at the 28th day to collect blood serum, bronchoalveolar lavage fluid (BALF), and pulmonary tissues. Then, the severity of pulmonary fibrosis and the expression of nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2) in the pulmonary tissues were detected. Western blot analysis quantified the expressions of fibronectin and alpha-smooth muscle actin (α-SMA). The levels of 4-hydroxynonenal (4-HNE), glutathione (GSH), superoxide dismutase (SOD), TGF-β and hydroxyproline (HP) in the BALF, and pulmonary tissues were measured. The expression levels of Nrf2 and its downstream genes, hemeoxygenase-1 (HO-1) and NAD (P) H: quinone oxidoreductase (NQO1) were examined. CHE at the concentration of 0.375 or 0.75 mg/kg/d could attenuate pulmonary fibrosis. CHE injection reduced the expression levels of fibronectin, α-SMA, and TGF-β, upregulated the levels of SOD and GSH and decreased the levels of 4-HNE and HP. Also, CHE increased the expressions of Nrf2, HO-1, and NQO1. Treatment of Nrf2/antioxidant response element (ARE) inhibitor could block the Nrf2/ARE signaling pathway, thus perturbing the inhibition of CHE on BLM-stimulated pulmonary fibrosis in mice. CHE alleviates BLM-induced pulmonary fibrosis in mice through activating the Nrf2/ARE pathway to increase the activity of antioxidant enzymes.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011658 Pulmonary Fibrosis A process in which normal lung tissues are progressively replaced by FIBROBLASTS and COLLAGEN causing an irreversible loss of the ability to transfer oxygen into the bloodstream via PULMONARY ALVEOLI. Patients show progressive DYSPNEA finally resulting in death. Alveolitis, Fibrosing,Idiopathic Diffuse Interstitial Pulmonary Fibrosis,Fibroses, Pulmonary,Fibrosis, Pulmonary,Pulmonary Fibroses,Alveolitides, Fibrosing,Fibrosing Alveolitides,Fibrosing Alveolitis
D001992 Bronchoalveolar Lavage Fluid Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung. Alveolar Lavage Fluid,Bronchial Lavage Fluid,Lung Lavage Fluid,Bronchial Alveolar Lavage Fluid,Lavage Fluid, Bronchial,Lavage Fluid, Lung,Pulmonary Lavage Fluid,Alveolar Lavage Fluids,Bronchial Lavage Fluids,Bronchoalveolar Lavage Fluids,Lavage Fluid, Alveolar,Lavage Fluid, Bronchoalveolar,Lavage Fluid, Pulmonary,Lavage Fluids, Alveolar,Lavage Fluids, Bronchial,Lavage Fluids, Bronchoalveolar,Lavage Fluids, Lung,Lavage Fluids, Pulmonary,Lung Lavage Fluids,Pulmonary Lavage Fluids
D003094 Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH). Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013482 Superoxide Dismutase An oxidoreductase that catalyzes the reaction between SUPEROXIDES and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. Hemocuprein,Ag-Zn Superoxide Dismutase,Cobalt Superoxide Dismutase,Cu-Superoxide Dismutase,Erythrocuprein,Fe-Superoxide Dismutase,Fe-Zn Superoxide Dismutase,Iron Superoxide Dismutase,Manganese Superoxide Dismutase,Mn-SOD,Mn-Superoxide Dismutase,Ag Zn Superoxide Dismutase,Cu Superoxide Dismutase,Dismutase, Ag-Zn Superoxide,Dismutase, Cobalt Superoxide,Dismutase, Cu-Superoxide,Dismutase, Fe-Superoxide,Dismutase, Fe-Zn Superoxide,Dismutase, Iron Superoxide,Dismutase, Manganese Superoxide,Dismutase, Mn-Superoxide,Dismutase, Superoxide,Fe Superoxide Dismutase,Fe Zn Superoxide Dismutase,Mn SOD,Mn Superoxide Dismutase,Superoxide Dismutase, Ag-Zn,Superoxide Dismutase, Cobalt,Superoxide Dismutase, Fe-Zn,Superoxide Dismutase, Iron,Superoxide Dismutase, Manganese

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