Table 2.

Compounds with direct wound-healing effects in zebrafish models.

Agent	Model	Treatment Mode	Findings	Reference
Natural products
Panax ginseng	Tail fin amputation in zebrafish larva	Incubation medium	Potent anti-inflammatory effects similar to beclomethasone No effect on regeneration	[53]
Panax ginseng	Zebrafish embryos	Incubation medium	Promotes angiogenesis Increase in sub-intestinal vascular growth (dosage 500 μg/mL)	[56]
Curcuma longa	Caudal fin transection in adult zebrafish	Topical application	Maximum fin regeneration with 500 μg of the aqueous extract on day 5 Drastic neutrophil migration reduction on day 5	[57]
Ethanol extract Propolis (Trigona laeviceps)(EEP)	Caudal fin amputation in hyperglycemia model (induced by alloxan and glucose) in adult zebrafish	Water immersion	Increased fin regeneration Increased gene expression involved in wound healing and regeneration (shha, igf2a, bmp2b, and col1a2)	[62]
Nanoparticles
Silver nanoparticles	Caudal fin regeneration model in adult 3-month-old zebrafish	Water immersion	Increased fin regeneration Increased gene expression involved in wound healing and regeneration	[72]
Silver nanoparticles	Laser-induced wound injury, posterior to the gill area in adult zebrafish	Water immersion and direct skin application	Faster wound closure at 5, 10, and 20 dpw by both AgNPs application methods AgNPs by immersion have a higher wound-healing activity Expression of wound-healing genes (TGF-β and MMP -13 and -9), proinflammatory cytokines (IL-1β and TNF-α), and antioxidant enzymes SOD and catalase	[37]
Spirulina maxima-derived pectin nanoparticles (SmPNPs)	Laser-induced wound at the left flank in adult zebrafish	Direct skin application	Rapid wound closure at 7, 10, 14, and 24 dpw Significant wound healing percentage compared to the vehicle at 10 dpw Histologically, rapid re-epithelialization in the SmPNPs-treated group at 7 dpw Upregulated wound-healing marker in SmPNPs treated group (tgfβ1, timp2b, mmp9, tnfα, il1β, ccl34a.4, and ccl34b.4)	[74]
Spirulina maxima-derived marine pectin (Smp)	Fin regeneration model in zebrafish larvae; laser-induced wound in adult zebrafish	Topical application	Enhanced fin regeneration upon Smp treatment at 3 dpw in zebrafish larvae SMP accelerate open-skin wound closure in adult zebrafish SMP-treated fish exhibited rapid re-epithelization at 2 dpw Upregulation of wound-healing marker (tgfβ1, timp2b, mmp9, tnfα, il1β, ccl34a.4, and ccl34b.4)	[43]
Formulated drug
Nocadazole	Caudal fin amputation in zebrafish embryos	Incubation medium	Nocodazole significantly increased the circulatory neutrophils at the wounded fin	[78]