ReferenceID 5604
Systems pharmacology approach uncovers Ligustilide attenuates experimental colitis in mice by inhibiting PPARγ-mediated inflammation pathways
Cell Biol Toxicol
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
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- Reference Id
- 5604
- Evidence Id
- 22194
- Core Evidence Id
- 22194
- Source Reference Id
- 4420
- Herb2 Reference Id
- HBREF005217
- Subject Paper Key
- HBIN033198_33130971
- Pubmed Id
- 33130971
- Doi
- 10.1007/s10565-020-09563-z
- Paper Title
- Systems pharmacology approach uncovers Ligustilide attenuates experimental colitis in mice by inhibiting PPARγ-mediated inflammation pathways
- Paper Abstract
- 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-1beta, IL-6, and TNF-alpha. Subsequently, the network analysis helped to validate that LIG alleviated colitis by inhibiting NF-kappaB and MAPK/AP-1 pathway through activating PPARgamma, which were further confirmed in RAW 264.7 cells and bone marrow-derived macrophages in vitro. In summary, this study reveals that LIG activated PPARgamma to inhibit the activation of NF-kappaB 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 This study suggested novel computational and experimental pharmacology approaches to identify potential IBD therapeutic agents by exploiting polypharmacology of natural products. We demonstrated that LIG could attenuate inflammation in IBD by inhibiting NF-kappaB and AP-1 pathways via PPARgamma activation to reduce the expression of pro-inflammatory cytokines in macrophages. These findings offer comprehensive pre-clinical evidence that LIG may serve as a promising candidate for IBD therapy in the future. Graphical headlights: 1. Systems pharmacology uncovered Ligustilide attenuates experimental colitis in mice. 2. Network-based analysis predicted the mechanism of Ligustilide against IBD, which was validated by inhibiting PPARgamma-mediated inflammation pathways. 3. Ligustilide activated PPARgamma to inhibit NF-kappaB and AP-1 activation thus eventually alleviated DSS-induced colitis.4. Ligustilide has promising activities and may serve as a candidate for the treatment of IBD.
- Journal
- Cell Biol Toxicol
- Publish Year
- 2021
- Experiment Subject
- mouse; raw 264.7 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Chronic Idiopathic Disorder; Inflammatory Bowel Disease; Colitis; Inflammation In The Gastro-intestinal Tract; Ibd Disease
- Paper Title Cn
- Paper Title En
- Systems pharmacology approach uncovers Ligustilide attenuates experimental colitis in mice by inhibiting PPARγ-mediated inflammation pathways
- Bilingual Status
- semi_complete