title: Kegan Liyan oral liquid ameliorates lipopolysaccharide-induced acute lung injury through inhibition of TLR4-mediated NF-κB signaling pathway and MMP-9 expression.
abstract: BACKGROUND
  Kegan Liyan oral liquid (KGLY), a Chinese prescription modified from classic formulas Yin-Qiao-San (from TCM classic Wenbing Tiaobian) and Shen-Jie-San (first mentioned in Shanghan Wenyi Tiaobian), has been reported to exert heat-clearing and detoxifying effects and used extensively for the treatment of severe pulmonary diseases in clinics including influenza, cough and pneumonia.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the protective effect of KGLY on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice and to illuminate the underlying mechanisms.
  
  
  METHODS
  Mice were orally administrated with KGLY (50, 100 and 150mg/kg) before intratracheal instillation of LPS. 24h post LPS challenge, lung tissues and the bronchoalveolar lavage fluid (BALF) were collected for lung wet/dry (W/D) weight ratio, histopathological examinations and biochemical analyses. The cell counts, protein concentration, interleukin-1β (IL-1β), interleukin-6 (IL-6), necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2) in BALF, superoxide dismutase (SOD), glutathione (GSH), myeloperoxidase (MPO) and malondialdehyde (MDA) levels were detected. Meanwhile, the activation of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), as well as matrix metalloproteinases 9 (MMP-9) were determined by western blot assay.
  
  
  RESULTS
  KGLY significantly prolonged mice survival time and ameliorated LPS-induced edema, thickening of alveolar septa and inflammatory cell infiltration in a dose-dependent manner. Additionally, KGLY markedly attenuated LPS-induced acute pulmonary inflammation via decreasing the expressions of cytokines and chemokines (IL-1β, IL-6, TNF-α, and MIP-2), enhanced the activities of anti-oxidative indicators (SOD and GSH), suppressed the levels of MPO and MDA, and down-regulated the expressions of TLR4, NF-κB and MMP9.
  
  
  CONCLUSIONS
  The results suggested that the relieving effect of KGLY against LPS-induced ALI might be partially due to suppression of oxidative stress and inflammatory response, inhibition of TLR4-mediated NF-κB activation, and down-regulation of MMP9 expression, indicating it may be a potential therapeutic agent for ALI.
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, PR China. Electronic address: 985958620@qq.com.
authors.forename: Xie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, PR China. Electronic address: 936316352@qq.com.
authors.forename: Chao-Yue
authors.initials: CY
authors.lastname: Sun
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. Electronic address: yongbinzhang@gzucm.edu.cn.
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, PR China. Electronic address: 604041882@qq.com.
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Guo
authors.affiliation: Guangdong Medical Laboratory Animal Center, Foshan 528248, PR China. Electronic address: 345375526@qq.com.
authors.forename: Xue-Xuan
authors.initials: XX
authors.lastname: Feng
authors.affiliation: Guangzhou Wanglaoji Pharmaceutical Company Limited, Guangzhou 510450, PR China. Electronic address: 691789232@qq.com.
authors.forename: Shao-Zhong
authors.initials: SZ
authors.lastname: Peng
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, PR China. Electronic address: 466754442@qq.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Guangzhou Wanglaoji Pharmaceutical Company Limited, Guangzhou 510450, PR China. Electronic address: zrbb0819@sina.com.
authors.forename: Rong-Bo
authors.initials: RB
authors.lastname: Zheng
authors.affiliation: Guangzhou Wanglaoji Pharmaceutical Company Limited, Guangzhou 510450, PR China. Electronic address: Chenwp@gpc.com.cn.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Chen
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, PR China. Electronic address: suziren@gzucm.edu.cn.
authors.forename: Zi-Ren
authors.initials: ZR
authors.lastname: Su
authors.affiliation: Guangzhou Wanglaoji Pharmaceutical Company Limited, Guangzhou 510450, PR China. Electronic address: xiaodanhuang@126.com.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Huang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000188:drug therapy; D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C548459:kegan liyan; D020780:Matrix Metalloproteinase 9
keywords: 4′-O-beta-glucopyranosyl-5-O-methylvisamminol (PubChem CID:21670038); Acute lung injury; Ammonium glycyrrhizinate (PubChem CID:62074); Baicalin (PubChem CID:64982); Caffeic acid (PubChem CID:689043); Chlorogenic acid (PubChem CID:1794427); Dexamethasone (PubChem CID:5743); Forsythin (PubChem CID:101712); Geniposide (PubChem CID:107848); Kegan Liyan oral liquid; Lipopolysaccharide; Matrix metalloproteinase 9; Menthol (PubChem CID:16666); Methanol (PubChem CID:887); Nuclear factor kappa B; Tectoridin (PubChem CID:5281810); Toll-like receptor 4