title: Tetrahydroberberrubine attenuates lipopolysaccharide-induced acute lung injury by down-regulating MAPK, AKT, and NF-κB signaling pathways.
abstract: Acute lung injury (ALI) is a life-threatening syndrome that is characterized by overwhelming lung inflammation and increased microvascular permeability, which causes a high mortality worldwide. Here, we studied the protective effect of tetrahydroberberrubine (THBru), a berberine derivative, on a mouse model of lipopolysaccharide (LPS)-induced acute lung injury that was established in our previous studies. The results showed that a single oral administration of THBru significantly decreased the lung wet to dry weight (W/D) ratio at doses of 2, 10 and 50mg/kg administered 1h prior to LPS challenge (30mg/kg, intravenous injection). Histopathological changes, such as pulmonary edema, infiltration of inflammatory cells and coagulation, were also attenuated by THBru. In addition, THBru markedly decreased the total cell counts, total protein and nitrate/nitrite content in bronchoalveolar lavage fluid (BALF), significantly decreased tumor necrosis factor-α (TNF-α) and nitrate/nitrite content in the plasma, and reduced the myeloperoxidase (MPO) activity in the lung tissues. Additionally, THBru (10μM) significantly decreased the content of TNF-α and nitric oxide (NO) in LPS-induced THP-1 cells in vitro. Moreover, THBru significantly suppressed the activation of the MAPKs JNK and p38, AKT, and the NF-κB subunit p65 in LPS-induced THP-1 cells. These findings confirm that THBru attenuates LPS-induced acute lung injury by inhibiting the release of inflammatory cytokines and suppressing the activation of MAPKs, AKT, and NF-κB signaling pathways, which implicates it as a potential therapeutic agent for ALI or sepsis.
authors.affiliation: State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639, Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639, Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Sulan
authors.initials: S
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639, Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639, Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639, Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639, Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639, Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639, Longmian Road, Nanjing, 211198, P.R. China. Electronic address: boyangyu59@163.com.
authors.forename: Boyang
authors.initials: B
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639, Longmian Road, Nanjing, 211198, P.R. China. Electronic address: junpingkou@163.com.
authors.forename: Junping
authors.initials: J
authors.lastname: Kou
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D002452:Cell Count; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011654:Pulmonary Edema / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D001599:Berberine; D009569:Nitric Oxide; D009195:Peroxidase; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C000613728:tetrahydroberberrubine
keywords: Acute lung injury; Berberine; Lipopolysaccharide; Signaling pathways; THP-1 cells; Tetrahydroberberrubine