Table 1.
Summary of potential NETs-targeted therapies in UC.
| Modulation on NETs | Targets | NETs treatment | Dose/concentration | Models and participants | Mechanism of action | References |
|---|---|---|---|---|---|---|
| Inhibit NETs formation | PAD4 | Cl-amidine | 5, 25, and 75 mg/kg/day (mice) | DSS-induced colitis mice | Inhibition of PAD activity and protein citrullination | (148) |
| Cl-amidine | 30 mg/kg/day (mice) | TNBS-induced colitis mice | PAD4↓, Cit-H3↓, MPO↓, TNF-α↓, IL-1β↓, IL-6↓, IL-17A↓, IFN-γ↓, IL-10↑ |
(149) | ||
| Cl-amidine | 30 mg/kg/day (mice) | TNBS-induced colitis mice | Cit-H3↓, MPO↓, IL-1β↓ | (150) | ||
| streptonigrin | 0.4 mg/kg/day (mice) | DSS-induced colitis mice | citH3↓, LCN-2↓, TNF-α↓, IL-1β↓ | (98) | ||
| H2S donor | 18.75 µM/kg/day (rat) | TNBS-induced colitis rat | PAD4↓, Cit-H3↓, MPO↓, NF-κB↓, HMGB1↓ | (151) | ||
| Huang Qin Decoction | 500, 1000, and 1500 mg/kg/day (mice) | AOM/DSS-generated CAC mice |
PAD4↓, Cit-H3↓, MPO-DNA complex↓, TNF-α↓, IL-1β↓, MMP-9↓, ZO-1↑, occludin↑ | (152) | ||
| ROS | 5-aminosalicylic acid | 0.005, 0.25, and 0.5 mM (cell) | Human peripheral blood neutrophil | ROS↓, superoxide↓ | (153) | |
| Cyclosporine A | not mentioned (mice) 100 nM (cell) |
DSS-induced acute colitis mice, peripheral blood neutrophil from UC patients |
P53↑, G6PD↓, ROS↓, Cit-H3↓, NE↓, TNF-α↓, IL-1β↓, |
(102) | ||
| butyrate | 200 mM in drinking water (mice) | DSS-induced acute colitis mice | ROS↓, CitH3↓, IL-6↓, TNF-α↓, IFN-γ↓, CXCL1↓, |
(154) | ||
| Ne | berberine | 1 mg/kg/day (mice) | DSS-induced IBD mice | NE↓, MPO↓, CitH3↓ | (104) | |
| TNF-α | infliximab | 5 mg/kg at weeks 0, 2 and 6 | UC patients | PAD4↓, Cit-H3↓, MPO↓ | (98) | |
| FcRn | anti-Fc-mAb | 80 and 160 μg/kg/7 days | DSS-induced UC rat | ANCA↓, PAD4↓, Cit-H3↓, MPO↓, NE↓, TNF-α↓, CRP↓ |
(105) | |
| MPO | Ferulic acid | 50mg/kg/day (mice) | DSS-induced colitis mice | MPO-DNA complex↓, Il-17↓, Il-22↓ | (155) | |
| Degrade NETs | DNA matrixes | DNase I | 250 U, qod (mice) | DSS-induced colitis mice; TNBS-induced colitis mice |
MPO-DNA complex↓, CitH3↓, TNF-α↓, IL-1β↓, ZO-1↑, occludin↑ |
(103) |
| DNase 1 | 65 U DNase 1, qod (mice) | DSS-induced colitis mice | MMP-9↓, TNF-α↓, IL-6↓, MCP-1↓, IL-1β↓, CXCL2↓, CXCL10↓ | (101) | ||
| staphylococcal nuclease | 25 and 75 mg/kg/day (mice) | DSS-induced UC mice | MPO↓, NE↓, TNF-α↓, IL-6↓, IL-1β↓, ZO-1↑, occludin↑ |
(156) |