title: Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways.
abstract: Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on lipopolysaccharide (LPS)-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum were reduced by andrographolide sulfonate administration. mRNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase (MAPK) as well as p65 subunit of nuclear factor-κB (NF-κB). In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Hang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Guo
authors.affiliation: Jiangxi Qingfeng Pharmaceutical Co., Ltd., Ganzhou 341000, China; State Key Laboratory of Innovative Nature Medicine and TCM Injections, Jiangxi Qingfeng Pharmaceutical Co., Ltd., Ganzhou, 341000, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Jiangxi Qingfeng Pharmaceutical Co., Ltd., Ganzhou 341000, China; State Key Laboratory of Innovative Nature Medicine and TCM Injections, Jiangxi Qingfeng Pharmaceutical Co., Ltd., Ganzhou, 341000, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
keywords: ALI, acute lung injury; ARDS, acute respiratory distress syndrome; Andrographolide sulfonate; BALF, bronchoalveolar lavage fluid; DSS, dextran sulfate sodium; H&E, hematoxylin & eosin; HRP, horseradish peroxidase; IL-6, interleukin-6; JNK, c-Jun N-terminal kinase; LPS, lipopolysaccharide; Lipopolysaccharide; Lung injury; MAPK; MAPK, mitogen-activated protein kinase; Mouse; NF-κB; NF-κB, nuclear factor-κB; TNBS, trinitrobenzenesulfonic acid; TNF, tumor necrosis factor