Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Mar Drugs
2018 Jan 08;161:. doi: 10.3390/md16010016.
Show Gene links
Show Anatomy links
Effect of Low Molecular Weight Oligopeptides Isolated from Sea Cucumber on Diabetic Wound Healing in db/db Mice.
Li D
,
Li L
,
Xu T
,
Wang T
,
Ren J
,
Liu X
,
Li Y
.
???displayArticle.abstract???
Impaired wound healing is a major clinical problem in patients with diabetes and is the leading cause of lower limb amputation. This study is aimed to observe the effects of small molecule oligopeptides isolated from sea cucumber (SCCOPs) on the wound healing process in diabetic mice. Ninety db/db male mice were divided into five groups, including the model control group, whey protein group (0.50 g/kg) and three SCCOPs dose groups (0.25 g/kg, 0.50 g/kg and 1.00 g/kg). Additionally, 18 db/m male mice were used as normal control group. After full-thickness incisions on the dorsum, mice in SCCOPs-treated groups were intragastrically administered SCCOPs, while others were administered vehicle or whey protein. Mice were sacrificed on days 4, 7 and 14. The wound healing condition, inflammatory response, angiogenesis, collagen deposition, oxidative stress and nutritional status were evaluated. A pathological report showed increased vascularisation, collagen deposition and epithelialisation in SCCOPs-treated groups. SCCOPs-treated mice showed decreased C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, chemokine (C-C motif) ligand 2 (CCL2) and reactive oxygen species (ROS) contents, and increased IL-10, stromal cell-derived factor-1 alpha (SDF-1α), nitric oxide (NO), albumin (ALB), prealbumin (PA) and transferrin (TRF) levels and vascular endothelial growth factor (VEGF) expression. All parameters were significant (p < 0.05) in comparison to model control group. These results suggest that treatment with SCCOPs can promote significant wound healing in diabetic mice.
Figure 1. Representative macroscopic images of wounds in mice on days 4, 7 and 14. (SCCOPs, small molecule oligopeptides isolated from sea cucumber; NC, normal control group; MC, model control group; WP, 0.50 g/kg whey protein group; SCCOPs-L, 0.25 g/kg SCCOPs group; SCCOPs-M, 0.50 g/kg SCCOPs group; SCCOPs-H, 1.00 g/kg SCCOPs group).
Figure 2. Representative micrograph of haematoxylin and eosin-stained section of wounds in mice on days 4, 7 and 14. The incision site in MC showed irregular arrangement of collagen bundles were loosely packed, and wounds demonstrated decreased vascularisation and epithelialisation. The site of wounds in SCCOPs-treated mice showed more densely packed and compactly arranged collagen bundles with increased blood vessel formation and on-going epithelialisation, reflecting a more rapidly healing wound than that of MC. (Magnification, 40× and 200×; SCCOPs, small molecule oligopeptides isolated from sea cucumber; NC, normal control group; MC, model control group; WP, 0.50 g/kg whey protein group; SCCOPs-L, 0.25 g/kg SCCOPs group; SCCOPs-M, 0.50 g/kg SCCOPs group; SCCOPs-H, 1.00 g/kg SCCOPs group).
Figure 4. Serum IL-6 (A), IL-8 (B), TNF-α (C), CCL2 (D) and IL-10 (E) content in mice on days 4, 7 and 14. (IL-6, interleukin-6; IL-8, interleukin-8; TNF-α, tumor necrosis factor-α; CCL2, chemokine (C-C motif) ligand 2; IL-10, interleukin-10; SCCOPs, small molecule oligopeptides isolated from sea cucumber; NC, normal control group; MC, model control group; WP, 0.50 g/kg whey protein group; SCCOPs-L, 0.25 g/kg SCCOPs group; SCCOPs-M, 0.50 g/kg SCCOPs group; SCCOPs-H, 1.00 g/kg SCCOPs group). Values are presented as mean ± SD. Values are presented as mean ± SD. * p < 0.05 versus NC, # p < 0.05 versus MC, ∆ p < 0.05 versus WP.
Figure 6. Expression of VEGF in wound tissue on day 14 after wounding in (a) NC; (b) MC; (c) WP; (d) SCCOPs-L; (e) SCCOPs-M and (f) SCCOPs-H. The VEGF immunolabeling was striking in SCCOPs-treated groups, whereas it was faint in MC and WP. (Magnification, 200×; VEGF, vascular endothelial growth factor; SCCOPs, small molecule oligopeptides isolated from sea cucumber; NC, normal control group; MC, model control group; WP, 0.50 g/kg whey protein group; SCCOPs-L, 0.25 g/kg SCCOPs group; SCCOPs-M, 0.50 g/kg SCCOPs group; SCCOPs-H, 1.00 g/kg SCCOPs group).
Figure 8. Collagen accumulation in wound areas in mice. (A) representative high power view light micrographs (Masson’s trichrome staining) in (a) NC, (b) MC, (c) WP, (d) SCCOPs-L, (e) SCCOPs-M and (f) SCCOPs-H on day 14 (Magnification, 200×); (B) hydroxyproline levels in the incision wound tissue in mice on days 4, 7 and 14. (SCCOPs, small molecule oligopeptides isolated from sea cucumber; NC, normal control group; MC, model control group; WP, 0.50 g/kg whey protein group; SCCOPs-L, 0.25 g/kg SCCOPs group; SCCOPs-M, 0.50 g/kg SCCOPs group; SCCOPs-H, 1.00 g/kg SCCOPs group). Values are presented as mean ± SD. Values are presented as mean ± SD. * p < 0.05 versus NC, # p < 0.05 versus MC, ∆ p < 0.05 versus WP.
Andersen,
Bioactive Egg Components and Inflammation.
2015, Pubmed
Andersen,
Bioactive Egg Components and Inflammation.
2015,
Pubmed
Ara,
Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny.
2003,
Pubmed
Baum,
Normal cutaneous wound healing: clinical correlation with cellular and molecular events.
2005,
Pubmed
Bitto,
Angiopoietin-1 gene transfer improves impaired wound healing in genetically diabetic mice without increasing VEGF expression.
2008,
Pubmed
Bordbar,
High-value components and bioactives from sea cucumbers for functional foods--a review.
2011,
Pubmed
,
Echinobase
Brem,
Cellular and molecular basis of wound healing in diabetes.
2007,
Pubmed
Castleberry,
Self-Assembled Wound Dressings Silence MMP-9 and Improve Diabetic Wound Healing In Vivo.
2016,
Pubmed
Costa,
Xanthohumol modulates inflammation, oxidative stress, and angiogenesis in type 1 diabetic rat skin wound healing.
2013,
Pubmed
Douraiswami,
C-reactive protein and interleukin-6 levels in the early detection of infection after open fractures.
2012,
Pubmed
Engler,
Matrix elasticity directs stem cell lineage specification.
2006,
Pubmed
Eo,
Ameliorative effect of dietary genistein on diabetes induced hyper-inflammation and oxidative stress during early stage of wound healing in alloxan induced diabetic mice.
2016,
Pubmed
Fosgerau,
Peptide therapeutics: current status and future directions.
2015,
Pubmed
Galeano,
Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse.
2008,
Pubmed
Galiano,
Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells.
2004,
Pubmed
Gottrup,
Present and new techniques and devices in the treatment of DFU: a critical review of evidence.
2012,
Pubmed
Greenhalgh,
Wound healing and diabetes mellitus.
2003,
Pubmed
Guo,
Stromal cell-derived factor 1 (SDF-1) accelerated skin wound healing by promoting the migration and proliferation of epidermal stem cells.
2015,
Pubmed
Hartmann,
Food-derived peptides with biological activity: from research to food applications.
2007,
Pubmed
He,
Sea cucumber (Codonopsis pilosula) oligopeptides: immunomodulatory effects based on stimulating Th cells, cytokine secretion and antibody production.
2016,
Pubmed
,
Echinobase
He,
Ginseng (Panax ginseng Meyer) oligopeptides regulate innate and adaptive immune responses in mice via increased macrophage phagocytosis capacity, NK cell activity and Th cells secretion.
2017,
Pubmed
Khantaphant,
Comparative study on the proteases from fish pyloric caeca and the use for production of gelatin hydrolysate with antioxidative activity.
2008,
Pubmed
Kim,
Isolation and characterization of antioxidative peptides from gelatin hydrolysate of Alaska pollack skin.
2001,
Pubmed
Li,
Pathophysiology of acute wound healing.
2007,
Pubmed
Lingaraj,
Vascular endothelial growth factor (VEGF) is expressed during articular cartilage growth and re-expressed in osteoarthritis.
2010,
Pubmed
Liu,
The anti-diabetic activity of oat β-d-glucan in streptozotocin-nicotinamide induced diabetic mice.
2016,
Pubmed
Morgan,
Naturally derived factors and their role in the promotion of angiogenesis for the healing of chronic wounds.
2013,
Pubmed
Murray,
Angiotensin converting enzyme inhibitory peptides derived from food proteins: biochemistry, bioactivity and production.
2007,
Pubmed
Romana-Souza,
Propranolol improves cutaneous wound healing in streptozotocin-induced diabetic rats.
2009,
Pubmed
Roy,
Biology of vascular endothelial growth factors.
2006,
Pubmed
Santos,
VEGF and VEGFR-2 (KDR) internalization is required for endothelial recovery during wound healing.
2007,
Pubmed
Senel,
Oxygen free radicals impair wound healing in ischemic rat skin.
1997,
Pubmed
Shigemura,
Dose-dependent changes in the levels of free and peptide forms of hydroxyproline in human plasma after collagen hydrolysate ingestion.
2014,
Pubmed
Stadelmann,
Physiology and healing dynamics of chronic cutaneous wounds.
1998,
Pubmed
Takahashi,
A retrospective cohort study of factors that affect healing in long-term care residents with chronic wounds.
2009,
Pubmed
Wise,
Orf virus IL-10 accelerates wound healing while limiting inflammation and scarring.
2014,
Pubmed
Witte,
Nitric oxide enhances experimental wound healing in diabetes.
2002,
Pubmed
Wood,
Pro-inflammatory chemokine CCL2 (MCP-1) promotes healing in diabetic wounds by restoring the macrophage response.
2014,
Pubmed
Zhang,
Oral administration of marine collagen peptides from Chum Salmon skin enhances cutaneous wound healing and angiogenesis in rats.
2011,
Pubmed
Zhang,
Oral administration of skin gelatin isolated from Chum salmon (Oncorhynchus keta) enhances wound healing in diabetic rats.
2011,
Pubmed
