title: The effective components of Huanglian Jiedu Decoction against sepsis evaluated by a lipid A-based affinity biosensor.
abstract: BACKGROUND
  Huanglian Jiedu Decoction (HJD), the classical recipe for relieving fever and toxicity, has been used for treating sepsis in China for sixteen years. However, the effective components of HJD have not been elucidated until now. Therefore, there is a need to elucidate the effective components of HJD against sepsis on animal models induced by endotoxin (LPS). The affinity force of the effective components of HJD with lipid A was evaluated by a biosensor.
  
  
  METHODS
  Lipid A is regarded as the bioactive center of LPS and is always used as a drug target. In order to obtain the effective components of HJD against sepsis, seven fractions from HJD were tested by a biosensor method for assessing the affinity for lipid A. After further separation, the components were isolated from high lipid A-binding fractions and their affinities to lipid A were assessed with the aid of a biosensor. Their activities were then assayed by an in vivo experiment administered through a tail vein injection. The levels of LPS, TNF-α, and IL-6 from the blood were found and pathology experiments were performed.
  
  
  RESULTS
  Three out of the seven fractions exhibited high lipid A-binding affinities. Berberine, baicalin and geniposide were obtained from the three high lipid A-binding fractions. The animal experiments indicated that the levels of LPS, TNF-α and IL-6 in the medicated treatment groups were much lower than that of the model group ((**)P<0.01). The medicated treatment groups exhibited stronger protective activities on varying organs in the animal model.
  
  
  CONCLUSIONS
  Berberine, baicalin and geniposide could neutralize LPS by binding with lipid A and then reduce the release of IL-6 and TNF-α induced by LPS. Furthermore, berberine, baicalin and geniposide exhibited protective activities on varying organs compared to the animal model established by the LPS-induced. These results validate that the components from HJD neutralized LPS and then depressed the release of IL-6 and TNF-α induced by LPS. This gives further evidence that HJD would be a suitable treatment for sepsis and protecting vital organs.
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD port, Dalian 116600, China. Electronic address: cgr800404@sohu.com.
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Chen
authors.affiliation: Department of Medicinal Chemistry, Virginia Commonwealth University, 23219, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD port, Dalian 116600, China.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Li
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD port, Dalian 116600, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jing
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD port, Dalian 116600, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD port, Dalian 116600, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, Virginia Commonwealth University, 23219, USA.
authors.forename: Brianna
authors.initials: B
authors.lastname: Mackie
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD port, Dalian 116600, China.
authors.forename: De-Qiang
authors.initials: DQ
authors.lastname: Dou
mesh_terms: D000818:Animals; D001599:Berberine / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D015374:Biosensing Techniques; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D005260:Female; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood; D039823:Iridoids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008050:Lipid A / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000473:pathology; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D015850:Interleukin-6; D039823:Iridoids; D008050:Lipid A; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C000605453:huanglian-jie-du decoction; C577686:interleukin-6, mouse; D001599:Berberine; C007835:geniposide; C038044:baicalin
keywords: Biosensor method; Huanglian Jiedu Decoction; Lipid A; Sepsis; The effective components