title: Water-soluble andrographolide sulfonate exerts anti-sepsis action in mice through down-regulating p38 MAPK, STAT3 and NF-κB pathways.
abstract: Andrographolide is a prescribed drug used for preventing and treating the common cold, influenza, viral infections or allergies. However, its poor water solubility enormously limits its bioavailability. In the present study, we aimed at examining and comparing the effect of andrographolide sulfonate (trade name: Xi-Yan-Ping Injection), a water-soluble form made from andrographolide through sulfonating reaction, on the treatment of murine sepsis model induced by lipopolysaccharide (LPS). Pretreatment with andrographolide sulfonate significantly decreased the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and transaminase activities in serum, attenuated liver and lung damage, and improved the survival of mice with experimental sepsis. Andrographolide sulfonate also remarkably reduced the expression levels of TNF-α, IL-1β, IL-6 and inducible nitric oxide synthase in the injured liver from septic mice. Moreover, andrographolide sulfonate time-dependently suppressed the activation of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK1/2) or c-Jun NH(2)-terminal kinase (JNK). Furthermore, pretreatment with andrographolide sulfonate markedly inhibited the activation of p65 subunit of nuclear factor-κB (NF-κB) as well as signal transducers and activators of transcription 3 (STAT3) in the injured liver from mice with endotoxic shock. Notably, andrographolide sulfonate showed a much stronger alleviation of LPS-induced sepsis in mice compared with andrographolide. Taken together, these results reveal that andrographolide sulfonate ameliorates sepsis in mice through suppressing p38 MAPK, STAT3 and NF-κB pathways and suggest that andrographolide sulfonate has an advantage of andrographolide for the treatment of endotoxin shock.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Guo
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.forename: Shaocheng
authors.initials: S
authors.lastname: Hong
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
authors.forename: Ning
authors.initials: N
authors.lastname: Xie
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004224:Diterpenes / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008107:Liver Diseases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D058566:Sacroiliitis; D018805:Sepsis / Q000188:drug therapy*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004224:Diterpenes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C030419:andrographolide; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases