Arbutin Ameliorates Murine Colitis by Inhibiting JAK2 Signaling Pathway

被引:22
作者
Wang, Liang [1 ,2 ]
Feng, Yuntao [1 ]
Wang, Jianwen [1 ]
Luo, Tenglong [1 ]
Wang, Xinyue [1 ]
Wu, Mengze [1 ]
Wang, Runxia [1 ]
Chen, Dapeng [1 ]
Li, Jiyan [3 ]
Wang, Jingyu [1 ,2 ]
机构
[1] Dalian Med Univ, Comparat Med Dept Researching & Teaching, Dalian, Peoples R China
[2] Dalian Med Univ, Lab Anim Ctr, Dalian, Peoples R China
[3] Dalian Hosp Tradit Chinese Med, Dept Spleen & Stomach, Dalian, Peoples R China
关键词
dextran sulfate sodium; JAK2; stat3; apoptosis; epithelium; arbutin; inflammatory bowel disease; sulfasalazine; INFLAMMATORY-BOWEL-DISEASE; DEXTRAN SULFATE SODIUM; CROHNS-DISEASE; EXPRESSION; APOPTOSIS; MECHANISM;
D O I
10.3389/fphar.2021.683818
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background and objective: Abnormal activation of Janus kinase 2 (JAK2) promotes the pathogenesis and progress of inflammatory bowel disease (IBD) by stimulating the cytokine traffic. Based on docking studies, arbutin, a natural product extracted from a traditional medicinal plant bearberry, was found to bind to JAK2. The study aimed to investigate the effects and mechanisms of regulating JAK2 by arbutin on colitis in mice.Methods: A mice colitis model was established to mimic human IBD. The mice freely drank water containing dextran sulfate sodium. Inflammation in epithelial (IEC6) and immune (RAW264.7) cells was analyzed following treatment with lipopolysaccharides (LPS).Results: Colitis symptoms, including body weight loss, increased disease activity index, and increased colon weight/length ratio, were significantly alleviated by arbutin. Mediators of colonic pro-inflammatory cytokines as well as apoptosis markers in colitis were suppressed by the glycoside. High expression of phosphorylated JAK2 in colitis was significantly reversed by arbutin. The effects of arbutin treatment on colitis were considerably inhibited by the JAK2 inhibitor AG490. LPS-induced inflammatory responses were also suppressed by arbutin, which was notably inhibited by the JAK2 inhibitor AG490.Conclusion: The findings obtained herein suggest the protective role of arbutin and provide novel insights into alternative colitis treatments, which involve inhibition of the JAK2 signaling pathway.
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页数:12
相关论文
共 38 条
[1]   The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 [J].
Alatab, Sudabeh ;
Sepanlou, Sadaf G. ;
Ikuta, Kevin ;
Vahedi, Homayoon ;
Bisignano, Catherine ;
Safiri, Saeid ;
Sadeghi, Anahita ;
Nixon, Molly R. ;
Abdoli, Amir ;
Abolhassani, Hassan ;
Alipour, Vahid ;
Almadi, Majid A. H. ;
Almasi-Hashiani, Amir ;
Anushiravani, Amir ;
Arabloo, Jalal ;
Atique, Suleman ;
Awasthi, Ashish ;
Badawi, Alaa ;
Baig, Atif A. A. ;
Bhala, Neeraj ;
Bijani, Ali ;
Biondi, Antonio ;
Borzi, Antonio M. ;
Burke, Kristin E. ;
Carvalho, Felix ;
Daryani, Ahmad ;
Dubey, Manisha ;
Eftekhari, Aziz ;
Fernandes, Eduarda ;
Fernandes, Joao C. ;
Fischer, Florian ;
Haj-Mirzaian, Arvin ;
Haj-Mirzaian, Arya ;
Hasanzadeh, Amir ;
Hashemian, Maryam ;
Hay, Simon, I ;
Hoang, Chi L. ;
Househ, Mowafa ;
Ilesanmi, Olayinka S. ;
Balalami, Nader Jafari ;
James, Spencer L. ;
Kengne, Andre P. ;
Malekzadeh, Masoud M. ;
Merat, Shahin ;
Meretoja, Tuomo J. ;
Mestrovic, Tomislav ;
Mirrakhimov, Erkin M. ;
Mirzaei, Hamed ;
Mohammad, Karzan A. ;
Mokdad, Ali H. .
LANCET GASTROENTEROLOGY & HEPATOLOGY, 2020, 5 (01) :17-30
[2]   Tight Junction Proteins and Signaling Pathways in Cancer and Inflammation: A Functional Crosstalk [J].
Bhat, Ajaz A. ;
Uppada, Srijayaprakash ;
Achkar, Iman W. ;
Hashem, Sheema ;
Yadav, Santosh K. ;
Shanmugakonar, Muralitharan ;
Al-Naemi, Hamda A. ;
Haris, Mohammad ;
Uddin, Shahab .
FRONTIERS IN PHYSIOLOGY, 2019, 9
[3]   "Do We Know Jack" About JAK? A Closer Look at JAK/STAT Signaling Pathway [J].
Bousoik, Emira ;
Aliabadi, Hamidreza Montazeri .
FRONTIERS IN ONCOLOGY, 2018, 8
[4]   Small-molecule agents for the treatment of inflammatory bowel disease [J].
Currie, Kevin S. ;
Patel, Leena ;
Sedillo, Kassandra F. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2019, 29 (16) :2034-2041
[5]   Histological evaluation in ulcerative colitis [J].
DeRoche, Tom C. ;
Xiao, Shu-Yuan ;
Liu, Xiuli .
GASTROENTEROLOGY REPORT, 2014, 2 (03) :178-192
[6]   α-Arbutin Protects Against Parkinson's Disease-Associated Mitochondrial Dysfunction In Vitro and In Vivo [J].
Ding, Yaqi ;
Kong, Deqin ;
Zhou, Tong ;
Yang, Nai-di ;
Xin, Chenqi ;
Xu, Jiajia ;
Wang, Qi ;
Zhang, Hang ;
Wu, Qiong ;
Lu, Xiaomei ;
Lim, Kahleong ;
Ma, Bo ;
Zhang, Chengwu ;
Li, Lin ;
Huang, Wei .
NEUROMOLECULAR MEDICINE, 2020, 22 (01) :56-67
[7]   Ginsenoside Rb1 alleviates colitis in mice via activation of endoplasmic reticulum-resident E3 ubiquitin ligase Hrd1 signaling pathway [J].
Dong, Jian-yi ;
Xia, Kai-jun ;
Liang, Wei ;
Liu, Lu-lu ;
Yang, Fang ;
Fang, Xue-sheng ;
Xiong, Yong-jian ;
Wang, Liang ;
Zhou, Zi-juan ;
Li, Chang-yi ;
Zhang, Wei-dong ;
Wang, Jing-yu ;
Chen, Da-peng .
ACTA PHARMACOLOGICA SINICA, 2021, 42 (09) :1461-1471
[8]   Impact of immune-mediated diseases in inflammatory bowel disease and implications in therapeutic approach [J].
Garcia, M. J. ;
Pascual, M. ;
Del Pozo, C. ;
Diaz-Gonzalez, A. ;
Castro, B. ;
Rasines, L. ;
Crespo, J. ;
Rivero, M. .
SCIENTIFIC REPORTS, 2020, 10 (01)
[9]  
Garrett J.T., 2003, The Cherokee Herbal: Native Plant Medicine from the Four Directions
[10]   IL-6 and Stat3 Are Required for Survival of Intestinal Epithelial Cells and Development of Colitis-Associated Cancer [J].
Grivennikov, Sergei ;
Karin, Eliad ;
Terzic, Janos ;
Mucida, Daniel ;
Yu, Guann-Yi ;
Vallabhapurapu, Sivakumar ;
Scheller, Juergen ;
Rose-John, Stefan ;
Cheroutre, Hilde ;
Eckmann, Lars ;
Karin, Michael .
CANCER CELL, 2009, 15 (02) :103-113