title: The anti-sepsis activity of the components of Huanglian Jiedu Decoction with high lipid A-binding affinity.
abstract: Huanglian Jiedu Decoction (HJD), one of the classic recipes for relieving toxicity and fever, is a common method for treating sepsis in China. However, the effective components of HJD have not yet been identified. This experiment was carried out to elucidate the effective components of HJD against sepsis. Thus, seven fractions from HJD were tested using a biosensor to test their affinity for lipid A. The components obtained that had high lipid A-binding fractions were further separated, and their affinities to lipid A were assessed with the aid of a biosensor. The levels of LPS in the blood were measured, and pathology experiments were conducted. The LPS levels and mRNA expression analysis of TNF-α and IL-6 of the cell supernatant and animal tissue were evaluated to investigate the molecular mechanisms. Palmatine showed the highest affinity to lipid A and was evaluated by in vitro and in vivo experiments. The results of the in vitro and in vivo experiments indicated that the levels of LPS, TNF-α and IL-6 of the palmatine group were significantly lower than those of the sepsis model group (p<0.01). The group treated with palmatine showed strong neutralizing LPS activity in vivo. The palmatine group exhibited stronger protective activity on vital organs compared to the LPS-induced animal model. This verifies that HJD is a viable treatment option for sepsis given that there are multiple components in HJD that neutralize LPS, decrease the release of IL-6 and TNF-α induced by LPS, and protect vital organs.
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD port, Dalian 116600, China.
authors.forename: Guirong
authors.initials: G
authors.lastname: Chen
authors.affiliation: Key Laboratory of Biological Invasions and Global Changes, College of Biological Science and Technology, Shenyang Agricultural University, Shenyang 110161, China. Electronic address: Xuyubin1988@126.com.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Xu
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: Department of Medicinal Chemistry, Virginia Commonwealth University, 23219, USA.
authors.forename: Brianna
authors.initials: B
authors.lastname: Mackie
authors.affiliation: Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xinchuan
authors.initials: X
authors.lastname: Zheng
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: 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: Xuetao
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D001600:Berberine Alkaloids / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000627:therapeutic use*; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008050:Lipid A / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D000067996:RAW 264.7 Cells; D018805:Sepsis / Q000628:therapy*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D001600:Berberine Alkaloids; D004365:Drugs, Chinese Herbal; D015850:Interleukin-6; D008050:Lipid A; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C000605453:huanglian-jie-du decoction; C005413:palmatine
keywords: Anti-sepsis activity; Huanglian Jiedu Decoction; LPS; Lipid A; Palmatine