Table 1.
List of potential anti-fibrotic agents that have been tested in murine or human intestinal models.
| Molecules | Mechanism of action | Model system | Outcome relevant to the gastrointestinal tract | References |
|---|---|---|---|---|
| AMA0825 | Rho-associated protein kinase inhibitor | Murine intestinal fibrosis | Prevention and reversal of intestinal fibrosis | [106] |
| Tranilast | Reduction of TGF- β activity | Pilot study in human CD patients | Reduced rate of symptom occurrence in asymptomatic strictures | [102] |
| GED-0507–34 Levo | PPARγ Receptor agonist | Murine intestinal fibrosis | Prevention of intestinal fibrosis | [107] |
| Il-36R antibody | Interleukin 36 receptor inhibition | Primary human cells and murine intestinal fibrosis | Prevention and reversal of intestinal fibrosis and reduction in profibrotic gene signatures in human fibroblasts | [104] |
| Thalidomide | Regulates multiple inflammatory and fibrosis pathways | Murine intestinal fibrosis | Regulation and reversal of intestinal fibrosis | [108] |
| Andrographolide sulfonate | Inhibits activation of macrophages, suppresses Th1/Th17 response, and down-regulates MAPKs and NF-κB pathways | Murine intestinal fibrosis | Prevention of intestinal fibrosis | [109,110] |
| EW-7197 | Transforming growth factor-β type I receptor kinase inhibitor | Murine intestinal fibrosis | Prevention of intestinal fibrosis | [111] |
| TM5275 | PAI-1 inhibition | Murine intestinal fibrosis | Reversal of intestinal fibrosis | [112] |
| Pirfenidone | Inhibits cell proliferation and collagen I production | In vitro primary human intestinal fibroblasts. | Inhibition of fibroblast growth and suppression of collagen production | [113] |
| Mouse p40 peptide-based vaccines | Sustained Blockage of IL-12 and IL-23 | Murine intestinal fibrosis | Prevention and reduction of intestinal fibrosis | [114–116] |
| Wu-Mei-Wan, a classic traditional Chinese herb medicine | Inhibition of colon fibroblast activation | Murine intestinal fibrosis | Prevent intestinal fibrosis | [117] |
| ICG-001 | TGF-β/ WNT signaling inhibition | Intestinal fibroblasts | Inhibition of β-catenin and collagen I production | [118] |
| Melanin-concentrating hormone antibody | Melanin-concentrating hormone blockage | Murine intestinal fibrosis | Reduction of collagen production and reduction of fibrosis | [119] |
| Daikenchuto (Da-Jian-Zhong-Tang) | Activating myofibroblast transient receptor potential ankyrin 1 channel | Murine intestinal fibrosis | Prevention of intestinal fibrosis | [120] |
| Losartan | Downregulation of TGF-β1 expression | Murine intestinal fibrosis | Prevention of intestinal fibrosis | [121] |
| Triptolide (PG490) | Anti-inflammatory and immunomodulatory activities | Murine intestinal fibrosis | Prevention and reversal of intestinal fibrosis | [122] |
| BGB324 | AXL Receptor tyrosine kinase inhibitor | Human colonic fibroblasts, murine intestinal fibrosis, Human intestinal organoid culture, colon resections of patients with CD | Prevention and reversal of intestinal fibrosis | [123] |
CD: Crohn’s disease; TGF- β: Transforming growth factor beta; PPARγ: Peroxisome Proliferator Activated Receptor Gamma; MAPK: mitogen-activated protein kinase; NF-κB: Nuclear factor kappa B.