title: Qingfei Xiaoyan Wan, a traditional Chinese medicine formula, ameliorates Pseudomonas aeruginosa-induced acute lung inflammation by regulation of PI3K/AKT and Ras/MAPK pathways.
abstract: Gram-negative pathogen-induced nosocomial infections and resistance are a most serious menace to global public health. Qingfei Xiaoyan Wan (QF), a traditional Chinese medicine (TCM) formula, has been used clinically in China for the treatment of upper respiratory tract infections, acute or chronic bronchitis and pulmonary infection. In this study, the effects of QF on Pseudomonas aeruginosa-induced acute pneumonia in mice were evaluated. The mechanisms by which four typical anti-inflammatory ingredients from QF, arctigenin (ATG), cholic acid (CLA), chlorogenic acid (CGA) and sinapic acid (SPA), regulate anti-inflammatory signaling pathways and related targets were investigated using molecular biology and molecular docking techniques. The results showed that pretreatment with QF significantly inhibits the release of cytokines (TNF-α and IL-6) and chemokines (IL-8 and RANTES), reduces leukocytes recruitment into inflamed tissues and ameliorates pulmonary edema and necrosis. In addition, ATG was identified as the primary anti-inflammatory agent with action on the PI3K/AKT and Ras/MAPK pathways. CLA and CGA enhanced the actions of ATG and exhibited synergistic NF-κB inactivation effects possibly via the Ras/MAPK signaling pathway. Moreover, CLA is speculated to target FGFR and MEK firstly. Overall, QF regulated the PI3K/AKT and Ras/MAPK pathways to inhibit pathogenic bacterial infections effectively.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300071, China; Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300071, China; Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300071, China; Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China.
authors.forename: Binfeng
authors.initials: B
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300071, China; Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300071, China; Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China.
authors.forename: Xiaoyao
authors.initials: X
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300071, China; Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300071, China; Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300071, China; Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Bai
keywords: ATG, arctigenin; Anti-inflammatory; CGA, chlorogenic acid; CLA, cholic acid; DMSO, dimethylsulfoxide; Dex, dexamethasone; ELISA, enzyme-linked immunosorbent assay; ESI, electrospray ionization; GA, genetic algorithm; HE, hematoxylin and eosin; KEGG, Kyoto Encyclopedia of Genes and Genomes; LB, Luria–Bertani; LEV, levofloxacin; Lung; MAPK, mitogen activated protein kinase; Mouse; NFATc1, nuclear factor of activated T cells c1; Network pharmacology; Ninj1, ninjurin1; PBS, phosphate-buffered saline; PI3K, phosphoinositide 3-kinase; PI3K/AKT pathway; Pathogenic bacterial  infection; QF, Qingfei Xiaoyan Wan; Ras/MAPK pathway; SARS, severe acute respiratory syndrome; SPA, sinapic acid; TCM, traditional Chinese medicine; TTBS, Tween 20/Tris-buffered saline; UPLC, ultra-performance liquid chromatography