Table 3.

Effects of marine organism-derived PDRN through in vivo studies.

PublicationYear	Source	Treatment	Model	Outcomes	Target	Ref
2016	O. mykiss	Treatment of fractional ablative CO2 laser	Skin wounded SD rats	↑ Wound healing ↑ Epithelial confluence ↑ Score on granulation tissue thickness ↑ Number of VEGF-positive cells ↓ Erythema and crusting ↑ Number of PECAM-1/CD31-positive microvessels ↑ Production of VEGF	Wound healing	[46]
2016	O. mykiss	-	Subcutaneous implanted nude mice	↑ Number of osteoblast and fibroblast attached to the surface of each particle ↑ Area ratio of NB ↑ Number of bone-forming cells ↑ Deposition and calcification of NB matrix ↑ Development of the blood vessels Newly formed COL matrix Observed a fibrous capsule in vicinity of dentin particles	Etc	[36]
2016	O. mykiss	Intra-colonic injection of DNBS (25 mg) or Oral administration of DSS (8%)	Colitis-induced SD rats	↓ Colitis-induced damage ↓ Lipid peroxidation and neutrophil infiltration ↓ Serum level of IL-1β and TNF-α ↓ Bcl-2 expression ↑ Activation of A2AR	Inflammatory disease	[1]
2017	O. mykiss	CdCl2 challenge (2 mg/kg)	BTB integrity-induced C57 BL/6J mice	↓ Phosphorylation of ERK ↓ Level of FSH and LH ↑ Serum concentration of TE and inhibin B ↑ Size of seminiferous tubules ↑ Johnsen’s score ↑ Number of spermatozoa ↓ Isolation of peripheral positive germ cell and macrophages ↓Immunoreactivity on Claudin-11, N-Cadherin, occludin, and TGF-β3 ↓ Fragmented junctions between adjacent sertoli cells	Etc	[38]
2017	O. mykiss	Intra-tracheal instillation of E. coli LPS (5 mg/kg)	Lung injured SD rats	↓ Lung injury score and DNA fragmentation ↓ Expression of caspase-3, -8, and -9 ↑ Bax/Bcl-2 expression ratio ↑ Expression of A2AR, IL-6, and TNF-α Observed patch intra-alveolar macrophages Observed normal-looking alveolar structures except hyperplasia of type II pneumocytes	Inflammatory disease	[6]
2017	O. mykiss	-	Skin wounded SD rats	↓ Infiltration and number of inflammatory cells ↓ Scar size ↓ Expression of HMGB-1 ↑ Expression of COL I and III	Wound healing	[9]
2017	A. sinensis	-	Calvarial defected Wistar rats	↑ Percentage of NB ↑ Production of OCN and OPN	Etc	[13]
2017	O. mykiss	-	Tendon injured SD rats	↑ CSA of the laceration sites ↑ Resistant to mechanical stress ↑ Stored energy	Wound healing	[43]
2018	O. keta	Injection of MIA (60 mg/mL)	OA induced SD rats	↓ Expression of IL-1β, MMP-3, MMP-7 ↓ Phosphorylation of ERK ↓ Production of COX-2, PGE2, and TNF-α ↑ Regularity in chondrocyte distribution	Etc	[21]
2018	O. mykiss	-	Skin wounded ICR mice	↑ Wound healing↓ Infiltration of inflammatory cells ↑ Expression of p63, TGF-β, and VEGF ↑ Neovascularization Observed clear re-epithelialization and granulation tissue proliferation	Wound healing	[47]
2018	O. keta	-	Tendon injured New Zealand white rabbits	↑ Regeneration of COL fibers ↑ Number of VEGF-positive cells and density of PECAM-1-positive microvessel ↓ Tendon tear size	Etc	[5]
2018	O. keta	Oral administration of IND (20 mg/kg)	GU induced SD rats	↓ mRNA and protein expression of A2AR, IL-1β, IL-6, TNF-α, and VEGF ↑ cAMP concentration ↑ Phosphorylation of CREB and PKA Regenerated GU-induced tissue	Etc	[35]
2018	A. sinensis	CdCl2 challenge (2 mg/kg)	Brain damaged C57 BL/6J mice	↓ Level of MDA ↑ Level of GSH and BDNF ↓ Expression of mTOR ↓ Brain edema and ↓ Neuronal morphological changes	Etc	[14]
2018	O. mykiss	-	Tendon injured New Zealand white rabbits	↓ Mean tendon tear size ↑ Number of VEGF-positive cells and density of PECAM-1 positive microvessel ↑ Walking distance and fast walking time	Etc	[41]
2018	O. keta	-	Skin wounded hairless mice	↑ COL production ↓ Lipid accumulation Observed a normal wound healing process	Wound healing	[27]
2018	O. keta	Removal of ovary and uterus & Administration of ZA (0.6 mg/mL)	Osteoporosis inducedSD rats	↓ Severity of the osteonecrosis ↓ Necrotic bone formation at defect sites ↑ Number of blood vessels ↑ Number of attached osteoclasts ↓ Number of detached osteoclasts ↑ Recovery bone remodeling	Etc	[7]
2019	O. keta	Chondrocutaneous section of composite tissue	New Zealand White rabbits	↑ Average viable area ↑ Number of capillaries Observed the blood flow signal at the margin of the composite grafts	Wound healing	[45]
2019	O. keta		Skin wounded Cg-+Leprdb/+Leprdb & m+/+Leprdb mice	↑ Granulation tissue and capillary blood vessels ↓ Diabetic wound depth ↑ Proliferation of fibroblasts and ↑ Thickness of the epidermis ↑ Closure of diabetic wound ↑ Epithelialization of the epidermis	Wound healing	[28]
2019	O. keta	Devascularization of the descending colon	Ischemic colitisinduced SD rats	↓ Mucosal damage ↓ COL deposition in the colonic tissue ↓ Expression of A2AR, caspase-3, COX-2, IL-1β, IL-6, TNF- α and VEGF ↑ Expression ratio of Bcl-2/Bax ↑ Phosphorylation of ERK	Inflammatory disease	[29]
2020	O. keta	Oral administration of IND (20 mg/kg)	GU induced SD rats	↑ Mucosal tissue regeneration ↓ Histological score and ulcer index ↓ Expression and level of IL-1β, IL-6, and TNF-α ↑ Expression and level of cAMP expression ↓ Activation of NF-κB and MAPK pathway ↓ Expression ratio of Bax/Bcl-2 ↑ Activation of A2AR	Etc	[37]
2020	O. keta	Intratracheal instillation of E. coli LPS (5 mg/kg)	Lung injured SD rats	↓ Lung injury score ↓ Number of WBC and BALF ↓ Expression of, cleaved caspase-3 and -9, IL-1β, IL-6, TNF-α ↑ Expression of cAMP ↓ Expression ratio of Bax/Bcl-2 ↑ Phosphorylation of CREB and PKA ↓ Activation of NF-κB and MAPK pathways ↓ DNA fragmentation	Etc	[39]
2020	O. mykiss	SNL or CPIP	Neuropathic pain induced C57/Bl6 mice	↓ Mechanical allodynia ↓ Expression of GFAP	Etc	[33]
2020	O. mykiss	Injury on ACL	OA inducedWistar albino rats	↓ Total Mankin scores and structural integrity ↓ Cellular changes and tidemark continuity	Etc	[34]
2020	O. mykiss	Intra-colonic instillation of DNBS (25 mg/0.8 mL)	Colitis induced SD rats	↑ Colon length ↓ Abnormal condition of colon ↓ Extent and severity of colon injury and epithelial and mucosal alterations ↓ Ulceration, size of colitis, and hyperaemia ↑ Bcl-2 positivity ↓ Activity of MPO and lipid peroxidation	Inflammatory disease	[2]
2020	O. keta	I.p. injection of CCl4 (10 mL/kg)	Liver injured C57BL/6 mice	↓ Expression of CYP2E1 and UCP2 ↓ Gross morphology of the liver ↓ Liver weight, index, and histopathological score ↓ Concentration of TNF-α, IL-1 and IL-6 ↓ Activation of NF-κB and MAPK pathway ↓ Expression of cleaved caspase-3 and -9 ↓ Expression ratio of Bax/Bcl-2	Etc	[4]
2020	O. keta	-	Skin wounded C57BLKS/J-db/db mice	↑ Wound closure rate ↑ Thickness of the granulation tissue ↓ Number of inflammatory cells ↑ COL density of the regenerated tissue ↓ Expression of MPO and TGF-β ↑ Expression of VEGF and α-SMA	Wound healing	[8]
2020	O. mykiss	-	Tendon injured New Zealand white rabbits	↓ Mean STTS ↑ COL synthesis ↑ Density of PECAM-1-positive microvessel ↑ Fast walking time and walking distance and speed	Etc	[42]
2020	O. mykiss	I.p. injection of CCl4 (10 mL/kg)	Lung injured ICR mice	↓ AST and ALT concentrations ↑ Expression of A2AR ↓ Expression of IL-1β, IL-6, and TNF-α ↓ Expression ratio of Bax/Bcl-2 ↓ Percentage of TUNEL-positive cells	Wound healing	[40]
2020	O. keta	-	Tendon injured SD rats	↑ Tactile threshold for the von Frey filament test ↑ Paw withdrawal latency ↓ Concentration of IL-6 and TNF-α ↓ Number of cleaved caspase-3- and -9-positive cells ↑ Expression of cAMP ↑ Phosphorylation of CREB and PKA ↓ Expression ratio of Bax/Bcl-2	Etc	[44]

↓: Decrease, ↑: Increase.