Systems pharmacology approach uncovers Ligustilide attenuates experimental colitis in mice by inhibiting PPARγ-mediated inflammation pathways

Huang，Yujie1,2,3; Zhang，Yifan1; Wan，Ting1; Mei，Yu1; Wang，Zihao4; Xue，Jincheng1; Luo，Yi1; Li，Min5; Fang，Shuhuan1; Pan，Huafeng1; Wang，Qi1,3; Fang，Jiansong1,3

2020

10.1007/s10565-020-09563-z

CELL BIOLOGY AND TOXICOLOGY   影响因子和分区

0742-2091

1573-6822

Inflammatory bowel disease (IBD) is a chronic idiopathic disorder causing inflammation in the gastro-intestinal tract, which is lack of effective drug targets and medications. To identify novel therapeutic agents against consistent targets, we exploited a systems pharmacology–driven framework that incorporates drug-target networks of natural product and IBD disease genes. Our in silico approach found that Ligustilide (LIG), one of the major active components of Angelica acutiloba and Cnidium Officinale, potently attenuated IBD. The following in vivo and in vitro results demonstrated that LIG prevented experimental mice colitis induced by dextran sulfate sodium (DSS) via suppressing inflammatory cell infiltration, the activity of MPO and iNOS, and the expression and production of IL-1β, IL-6, and TNF-α. Subsequently, the network analysis helped to validate that LIG alleviated colitis by inhibiting NF-κB and MAPK/AP-1 pathway through activating PPARγ, which were further confirmed in RAW 264.7 cells and bone marrow–derived macrophages in vitro. In summary, this study reveals that LIG activated PPARγ to inhibit the activation of NF-κB and AP-1 signaling thus eventually alleviated DSS-induced colitis, which has promising activities and may serve as a candidate for the treatment of IBD. Graphical abstract[Figure not available: see fulltext.].

Inflammatory bowel disease Ligustilide PPARγ Systems pharmacology

SCI

英语

其他

National Natural Science Foundation of China[82074278][81673627][81903890] ; Guangzhou Science Technology and Innovat i o n Commission Technology Research Projects[201805010005] ; youth scientific research training project of GZUCM[2019QNPY05] ; start-up support for scientific research of Xinglin Yong Scholar in Guangzhou University of Chinese Medicine[A1-AFD018181Z3926]

Cell Biology ; Toxicology

Cell Biology ; Toxicology

WOS:000583094200001

SPRINGER

MOLECULAR BIOLOGY & GENETICS

2-s2.0-85094852686

Scopus

1.Science and Technology Innovation Center,Guangzhou University of Chinese Medicine,Guangzhou,510405,China
2.College of Pharmacy,Shenzhen Technology University,Shenzhen,518118,China
3.Institute of Clinical Pharmacology,Guangzhou University of Chinese Medicine,Guangzhou,510405,China
4.Department of Chemistry,Southern University of Science and Technology,Shenzhen,518055,China
5.Clinical Medical College of Acupuncture Moxibustion and Rehabilitation,Guangzhou University of Chinese Medicine,Guangzhou,510006,China

Huang，Yujie,Zhang，Yifan,Wan，Ting,et al. Systems pharmacology approach uncovers Ligustilide attenuates experimental colitis in mice by inhibiting PPARγ-mediated inflammation pathways[J]. CELL BIOLOGY AND TOXICOLOGY,2020,37(1).

Huang，Yujie.,Zhang，Yifan.,Wan，Ting.,Mei，Yu.,Wang，Zihao.,...&Fang，Jiansong.(2020).Systems pharmacology approach uncovers Ligustilide attenuates experimental colitis in mice by inhibiting PPARγ-mediated inflammation pathways.CELL BIOLOGY AND TOXICOLOGY,37(1).

Huang，Yujie,et al."Systems pharmacology approach uncovers Ligustilide attenuates experimental colitis in mice by inhibiting PPARγ-mediated inflammation pathways".CELL BIOLOGY AND TOXICOLOGY 37.1(2020).