Parthenolide ameliorates Concanavalin A-induced acute hepatitis in mice and modulates the macrophages to an anti-inflammatory state.
Parthenolide, the principal sesquiterpene lactone present in medicinal plants such as feverfew, has anti-microbial, anti-inflammatory and anticancer activities. In the present study, we investigated the protective role of parthenolide against acute hepatitis in mice. Mice acute hepatitis were induced by Concanavalin A and treated by parthenolide in vivo. Results shown that parthenolide remarkably reduced the congestion and necroinflammation of the mice livers with Concanavalin A-induced acute hepatitis. Meanwhile, parthenolide treatment recover the liver function which indicated by decreased the serum alanine transaminase and alkaline phosphatase activities and promoted the expression of Ki67 in the livers of these mice. In addition, parthenolide administration suppressed the Concanavalin A-induced immune reaction, as indicated by the number of F4/80, CD49b and CD4 cells present in the liver. Furthermore, parthenolide also significantly reduced the expression of pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-17A, IL-1β and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in vitro. Moreover, parthenolide exposure decreased the phosphorylation of STAT3 and p38, and promoted the phosphorylation of p53 in RAW264.7 cells in vitro. In conclusion, parthenolide represents a drug candidate to protect the liver against Concanavalin A-induced acute hepatitis. The possible molecular mechanism involves the anti-inflammatory effects of parthenolide may by suppressing the STAT3/p38 signals and enhanced the p53 signals.
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Ministry of Education of China, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Diseases, Ministry of Education of China, Tianjin Medical University, Tianjin, China; Department of Blood Transfusion, Tianjin Medical University General Hospital, Tianjin, China.
Dan
D
Wang
School of Life Science, Shanxi Normal University, Linfen, China.
Huafeng
H
Wang
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Ministry of Education of China, Tianjin Medical University, Tianjin, China.
Shuyu
S
Fu
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Ministry of Education of China, Tianjin Medical University, Tianjin, China.
Xixi
X
Cheng
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Ministry of Education of China, Tianjin Medical University, Tianjin, China.
Fengrui
F
Yang
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Ministry of Education of China, Tianjin Medical University, Tianjin, China.
Qi
Q
Zhang
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Ministry of Education of China, Tianjin Medical University, Tianjin, China.
Yan
Y
Li
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Ministry of Education of China, Tianjin Medical University, Tianjin, China.
Zhenyi
Z
Xue
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Ministry of Education of China, Tianjin Medical University, Tianjin, China.
Lijuan
L
Zhang
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Ministry of Education of China, Tianjin Medical University, Tianjin, China; Union Stem Cells and Gene Engineering Co., Tianjin, China.
Wenjing
W
Huang
School of Life Science, Shanxi Normal University, Linfen, China.
Luhong
L
Yang
School of Life Science, Shanxi Normal University, Linfen, China.
Dongchen
D
Na
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Ministry of Education of China, Tianjin Medical University, Tianjin, China.
Yurong
Y
Da
Department of Biochemistry and Molecular Biology, Liaoning Key lab of Glycobiology and Glycoengn, Dalian Medical University, Dalian 116044, China. Electronic address: kongying@dmu.edu.cn.
Ying
Y
Kong
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Ministry of Education of China, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Diseases, Ministry of Education of China, Tianjin Medical University, Tianjin, China; Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China. Electronic address: rxzhang@tmu.edu.cn.
Rongxin
R
Zhang
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003208:Concanavalin A / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006505:Hepatitis / Q000188:drug therapy*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D000067996:RAW 264.7 Cells; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012717:Sesquiterpenes / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D050796:STAT3 Transcription Factor; D012717:Sesquiterpenes; C494087:Stat3 protein, mouse; D016159:Tumor Suppressor Protein p53; D003208:Concanavalin A; C002669:parthenolide; D048051:p38 Mitogen-Activated Protein Kinases
Acute hepatitis; Macrophage; Parthenolide; STAT3