PMID- 30036577 OWN - NLM STAT- MEDLINE DCOM- 20181113 LR - 20181211 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 225 DP - 2018 Oct 28 TI - Bai Hu Tang, Si Ni Tang, and Xue Bi Tang amplify pro-inflammatory activities and reduce apoptosis in endothelial cells in a cell culture model of sepsis. PG - 309-318 LID - S0378-8741(18)31663-5 [pii] LID - 10.1016/j.jep.2018.07.021 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis is a systemic inflammatory response of the body to a severe infection or massive tissue injury. Despite intensive research, sepsis continues to have a high mortality rate and successful treatment options are strongly needed. Bai Hu Tang (BHT), Si Ni Tang (SNT), and Xue Bi Tang (XBT) are ancient traditional Chinese formulas derived from Chinese herbs that are used to treat Sepsis, but their mechanisms of activity are largely unknown. AIM OF THE STUDY: We aimed to examine dose-dependent effects of BHT, SNT, and XBT in a cell culture model of Sepsis, with special focus on endothelial cell apoptosis and the expression of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)6, IL8, the surface adhesion molecule intercellular adhesion molecule-1 (ICAM-1) and endothelial-leukocyte adhesion molecule-1 (ELAM-1). MATERIAL AND METHODS: We stimulated THP1 monocytic cells with lipopolysaccharide (LPS, Escherichia coli (E. coli)) for 4 h and used the resulting culture medium to stimulate human umbilical vein endothelial cells (HUVECs). HUVECs were also simultaneously treated with hydrophilic concentrates of BHT, SNT or XBT. We evaluated the mRNA and protein expression levels of IL6, IL8, MCP-1, ICAM-1, and ELAM-1 and the activity of caspase 3/7, a marker of cell apoptosis, after stimulation and treatment. In addition, we stimulated cannulated veins from human umbilical cords for 24 h and treated them with BHT, SNT or XBT. Immunohistochemistry visualized expression of ICAM-1 and ELAM-1. RESULTS: The mRNA and protein levels of IL6, IL8, ICAM-1, and ELAM-1 were higher in stimulated HUVECs than in controls. Treating stimulated HUVECs with BHT, SNT or XBT induced an additional increase in IL6 (13- to 132-fold) and IL8 (17- to 32-fold) mRNA levels but did not influence their protein levels. In addition, BHT induced an additional increase in ICAM-1 mRNA (9-fold) expression, whereas XBT increased the mRNA and protein levels of ELAM-1 by 42-fold and 10-fold, respectively. Finally, caspase 3/7 levels, and therefore apoptosis, were up to 100% lower in cells treated with BHT than in the stimulated control (P < 0.001). CONCLUSION: The results of this study indicate that BHT, SNT, and XBT interfere in inflammatory pathways during septic processes by reducing the apoptotic effects of LPS and modifying the endothelial expression of pro-inflammatory cytokines and surface adhesion molecules. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Brislinger, Dagmar AU - Brislinger D AD - Department of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University Graz, Neue Stiftingtalstrasse 6, A-8010 Graz, Austria; Center of Biomedical Technology, Danube University Krems, Dr. Karl Dorrekstrasse 30, A-3500 Krems, Austria. Electronic address: dagmar.pfeiffer@medunigraz.at. FAU - Daxbock, Christine AU - Daxbock C AD - Department of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University Graz, Neue Stiftingtalstrasse 6, A-8010 Graz, Austria. FAU - Rossmanith, Eva AU - Rossmanith E AD - Center of Biomedical Technology, Danube University Krems, Dr. Karl Dorrekstrasse 30, A-3500 Krems, Austria. FAU - Stuckler, Manuela AU - Stuckler M AD - Department of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University Graz, Neue Stiftingtalstrasse 6, A-8010 Graz, Austria. FAU - Lang, Ingrid AU - Lang I AD - Department of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University Graz, Neue Stiftingtalstrasse 6, A-8010 Graz, Austria. FAU - Falkenhagen, Dieter AU - Falkenhagen D AD - Center of Biomedical Technology, Danube University Krems, Dr. Karl Dorrekstrasse 30, A-3500 Krems, Austria. LA - eng PT - Journal Article DEP - 20180720 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Cytokines) RN - 0 (Drugs, Chinese Herbal) RN - 0 (E-Selectin) RN - 0 (ICAM1 protein, rat) RN - 0 (Lipopolysaccharides) RN - 0 (Xue Bi Tang) RN - 0 (bai-hu-tang) RN - 0 (sini tang) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Apoptosis/drug effects MH - Cell Line MH - Cells, Cultured MH - Cytokines/genetics/metabolism MH - Drugs, Chinese Herbal/*pharmacology MH - E-Selectin/genetics/metabolism MH - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism MH - Humans MH - Intercellular Adhesion Molecule-1/genetics/metabolism MH - Lipopolysaccharides MH - Models, Biological MH - Sepsis/genetics/metabolism OTO - NOTNLM OT - Bai Hu Tang OT - Endothelium OT - Inflammation OT - Sepsis OT - Si Ni Tang OT - Xue Bi Tang EDAT- 2018/07/24 06:00 MHDA- 2018/11/14 06:00 CRDT- 2018/07/24 06:00 PHST- 2018/05/09 00:00 [received] PHST- 2018/07/17 00:00 [revised] PHST- 2018/07/18 00:00 [accepted] PHST- 2018/07/24 06:00 [pubmed] PHST- 2018/11/14 06:00 [medline] PHST- 2018/07/24 06:00 [entrez] AID - S0378-8741(18)31663-5 [pii] AID - 10.1016/j.jep.2018.07.021 [doi] PST - ppublish SO - J Ethnopharmacol. 2018 Oct 28;225:309-318. doi: 10.1016/j.jep.2018.07.021. Epub 2018 Jul 20.