n-Butanol extract from Folium isatidis inhibits lipopolysaccharide-induced inflammatory cytokine production in macrophages and protects mice against lipopolysaccharide-induced endotoxic shock.
Sepsis, which is caused by severe infection, is an important cause of mortality, but effective clinical treatment against sepsis is extremely limited. As the main component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) plays a major role in inflammatory responses. Studies have shown beneficial pharmacological effects for Folium isatidis. The present study further illuminated the effects of n-butanol extract from Folium isatidis in LPS-induced septic shock and identified the main active chemical components. Our study showed that pretreatment with n-butanol extract from Folium isatidis not only significantly inhibited LPS-induced tumor necrosis factor-α and interleukin-6 production but also markedly and dose dependently enhanced the recruitment of MyD88, the phosphorylation of extracellular signal-regulated kinase, and the degradation of IκB-α. Additionally, the extract exhibited dramatic protective effects against lung injury and death in mice with septic shock. Eight main active compounds were identified, including organic acids, glycoside, indolinones, and flavonoids. These findings provide a perspective on the respiratory protection offered by n-butanol extract from Folium isatidis in LPS-induced sepsis and outline a novel therapeutic strategy for the treatment of sepsis.
Department of Pediatrics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Lili
L
Jiang
Department of Pediatrics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Yili
Y
Lu
Department of Pediatrics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Jiahui
J
Jin
Department of Pediatrics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Lili
L
Dong
Department of Pediatrics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Fengli
F
Xu
Department of Pediatrics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Shuangshuang
S
Chen
Chemical Biology Research Center at The School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Zhanyue
Z
Wang
Chemical Biology Research Center at The School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Guang
G
Liang
Department of Pediatrics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Xiaoou
X
Shan
D020001:1-Butanol / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D031219:Isatis / Q000737:chemistry*; D008070:Lipopolysaccharides; D055370:Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D008517:Phytotherapy; D018515:Plant Leaves; D010946:Plants, Medicinal; D059748:Proteolysis; D012772:Shock, Septic / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D012997:Solvents / Q000737:chemistry*; D053719:Tandem Mass Spectrometry; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C000606205:Nfkbia protein, mouse; D012997:Solvents; D000072000:NF-KappaB Inhibitor alpha; D020001:1-Butanol; D048049:Extracellular Signal-Regulated MAP Kinases
Folium isatidis; inflammatory cytokine; sepsis