Wound Healing Properties of Selected Natural Products
Abstract
:1. Introduction
2. Curcuma longa
3. Vitamin E
4. Honey
5. Sea Cucumbers
6. The Advancements of Delivery System for the Selected Natural Products
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Wound Type | Animal Type | Intervention, Dose & Route | Findings | Study |
---|---|---|---|---|
Incisional wounds | C57BL/6J male mice | Curcumin (0.2 mg/mL) in Pluronic F127 hydrogel (20%), topical | Fast wound closure with well-formed granulation tissue dominated by collagen deposition and regenerating epithelium. | [25] |
Male Sprague-Dawley rats induced with dexamethasone intramuscularly | Curcumin with 0.1% ointment in polyethylene glycol base, topical | Curcumin significantly accelerated healing of wounds by reductions in wound width and gap length compared to controls. Curcumin treatment resulted in enhanced expression of TGF-β1 and TGF-β tIIrc in both normal and impaired healing by immunohistochemistry assessment. Macrophages in the wound bed showed an enhanced expression of TGF-β1 mRNA in curcumin-treated wounds as evidenced by in situ hybridization. | [26] | |
Male Sprague-Dawley rats | Curcumin/gelatin-blended nanofibrous mats (NMs), topical | The wounds treated with NMs showed regenerative process via (a) mobilization of wound site fibroblasts by activation of the Wnt signaling pathway, partly mediated through Dickkopf-related protein-1; (b) persistent inhibition of the inflammatory response through decreased expression of monocyte chemoattractant protein-1 by fibroblasts. | [35] | |
Excisional wounds | Male Wistar rats | 2% curcumin, topical | Incomplete but normal healing at 21 days of treatment | [29] |
2%, 3%, and 5% THC, topical | For 2% THC, progressive but incomplete healing was observed at 21 days of treatment | |||
2%, 3%, and 5% glucosyl-THC, topical | For 2% glucosyl-THC, complete healing of wounds at 21 days of treatment | |||
Sprague-Dawley male rats | Curcumin loaded oleic acid based polymeric (COP) bandage, topical | Increased wound reduction and enhanced cell proliferation in COP bandage-treated groups. Comparative acceleration in wound healing. Western blotting and semi quantitative PCR analysis clearly indicate that COP bandage can efficiently quench free radicals. | [32] | |
Streptozotocin-induced diabetic Swiss albino mice | Curcumin conjugated to hyaluronic acid (HA) (HA-Cur), topical | HA-Cur treated group showed well-formed granulation tissue rich in fibroblast, collagen and re-epithelialization was almost complete. | [34] | |
Whole-body γ irradiated Swiss albino mice | Curcumin suspended in 0.5% carboxy methylcellulose (CMC), 100 mg/kg orally before irradiation | Pre-treatment with curcumin significantly enhanced the rate of wound contraction, decreased mean wound healing time, increased synthesis of collagen, hexosamine, DNA, and nitric oxide and improved fibroblast and vascular densities. | [36] | |
Streptozotocin-induced diabetic male Wistar rats | 400 μL of curcumin (0.3%) in PF-127 hydrogel (25%), topical | Curcumin increased the wound contraction, levels of anti-inflammatory cytokine (IL-10), antioxidant enzymes (SOD, CAT and GPx) and decreased expressions of inflammatory cytokines/enzymes (TNF-α, IL-1β and MMP-9). Histopathologically, the curcumin-treated wounds showed better granulation tissue dominated by marked fibroblast proliferation and collagen deposition; wounds were covered by thick regenerated epithelial layer. | [37] |
Wound Type | Animal Type | Intervention, Dose & Route | Findings | Study |
---|---|---|---|---|
Excisional wounds | STZ-induced diabetic rats | α-tocopherol or PVE (200 mg/kg, oral) | Wound area was smaller at day 10; total protein content, collagen content SOD, and GPx activities were increased; MDA level was reduced; epidermis was well-formed and differentiated; re-epithelialization was completed; collagen was well-aligned. | [52] |
STZ-induced diabetic rats | Tocopherol (0.1 g, topical) | Wound closure rate was increased; total protein content and collagen fibers were increased; epithelialization was completed; epithelium was well-formed; interdigitation between epithelium and dermis layers was increased. | [51] | |
Alloxan-induced diabetic mice | γ-tocopherol (35 mg/kg, oral) | Wound closure rate was accelerated; levels of 4-HNE, NF-κB, TNF-α, & IL-1β were reduced; CAT level was increased. | [53] | |
Excisional wounds inoculated with MRSA | BALB/c mice | Vitamin E (60 mg/kg, oral) + tigecycline (2 mg/kg, i.p.) or daptomycin (7 mg/kg, i.p.) | Bacterial load was reduced; natural killer cell cytotoxicity and leukocyte populations were increased. | [67] |
Annatto tocotrienol (50 or 100 mg/kg, oral) + daptomycin (7 mg/kg, i.p.) | Bacterial load was reduced; natural killer cell cytotoxicity and wound repair markers were increased. | [66] | ||
Incisional wounds | Sprague-Dawley rats | Copper-doped borate bioactive glass/poly(lactic-co-glycolic acid) dressing loaded with vitamin E (3%, topical) | Wound closure rate was faster; number and density of new vessels were increased; new endothelium formed was longer; collagen deposition was thicker. | [57] |
Wistar rats | Medium chain triglycerides + linoleic acid + vitamin A, vitamin E + soy lecithin (0.1435 g, topical) | No acceleration in the process of tissue repair | [59] | |
STZ-induced diabetic rats | α-tocopherol (200 mg/kg, oral) | Rate of wound closure was accelerated; SOD, GPx, and CAT activities were increased; MDA level was reduced | [54] | |
Diabetic female C57BL/KsJ db+/db+ mice | Raxofelast, a synthetic analogue of vitamin E (15 mg/kg, i.p.) | Impaired wound healing was improved; breaking strength and collagen content of wound were higher; MDA level and MPO activity were decreased; re-epithelialization was moderate to complete; granulation tissue was well-organized; newly formed capillary vessels were observed; degree of infiltrated inflammatory cells was minimal. | [58] | |
Diabetic C57BL/KsJm/Leptdb (db/db) mice | Mono-epoxy-tocotrienol-α (MeT3α) (1 μmol) | Closure of wound area was enhanced. | [55] | |
Skin irradiated with argon and copper-vapor laser | Yorkshire pig | Vitamin E (5 mg/kg, i.m.; 2 mg/cm2, topical) | Healing time for laser injury was reduced. | [56] |
Wound Type | Animal Type | Intervention, Dose & Route | Findings | Study |
---|---|---|---|---|
Excisional wounds | Sprague-Dawley rats | Gelam honey (topical) | Wound healed earlier; wounds exhibited less scab; formation of thin scar. | [71] |
Honey (topical) | Wound healed in 21 days; collagen deposition and neovascularization was increased | [72] | ||
Pectin-honey hydrogel or Manuka honey (topical) | Wound area reduction rate was faster; entire surface of lesion was covered with new epithelium; dermis was well-developed; mature fibrous tissue proliferation was observed. | [93] | ||
Teucrium polium honey (topical) | Healed wound area percentage was increased; re-epithelialization, granulation tissue formation, collagen arrangement, fibrinoleukocytic exudates severity, vasculature hyperemia or congestion, dermis organization and epidermal appendage reappearance were improved | [94] | ||
Swiss Wistar rats | Acacia honey (5% or 10%, topical) | Period of epithelialization was reduced; wound contraction was increased. | [95] | |
Albino N-Mary Rats | Natural honey (10 mL) + zinc sulphate (36.3 mg) (topical) | Tensile strength was increased; collagen fibers, re-epithelialization and re-vascularization were increased. | [96] | |
Oryctolagus cuniculus rabbits | Natural honey (topical) | Tensile strength of wounds, wound contraction, neovascularization, fibroplasias, epithelialization, and formation of collagen were increased | [97] | |
New Zealand White rabbits | Honey (chestnut, blossom, or rhododendron) (topical) | Formation of granulation tissue, epithelialization, angiogenesis, and fibroplasia levels were increased on day 7. | [98] | |
BALB/cCrSlc mice | Indonesia pure honey (0.1 mL, topical) or Manuka honey (0.1 mL, topical) | Wound area was smaller; myofibroblasts and new blood capillaries were observed on day 3 | [71] | |
Japanese honey (Acacia, Buckwheat flour, or Chinese milk vetch) (0.1 mL, topical) | Wound size was reduced in inflammatory phase, increased in proliferative phase and then decreased in proliferative phase; some wounds were not completely covered with new epithelium. | [74] | ||
Japanese honey (Manuka, Acacia, Chinese milk vetch) (0.1 mL) + hydrocolloid dressing (topical) | Wound area was larger; numerous macrophages were observed; no significant difference in TNF-α and TGF-β levels; re-epithelialization and collagen deposition were delayed. | [75] | ||
Excisional wounds inoculated with MRSA | Wistar rats | Melipona scutellaris honey (0.1 mL/cm2, topical) | Bacterial count was decreased; levels of TNF-α, IL-1β, and IL-6 were increased; density of healing parameters (collagen, leukocytes and fibroblasts) were higher. | [99] |
Incisional wounds | Standardbred horses | Manuka honey (2 mL, topical) | Wound area was smaller; wounds healed faster. | [100] |
Sprague-Dawley rats | Teucrium polium honey (topical) | Healed wound area percentage was increased; re-epithelialization, granulation tissue formation, collagen arrangement, fibrinoleukocytic exudates severity, vasculature hyperemia or congestion, dermis organization and epidermal appendage reappearance were improved | [94] | |
Swiss Wistar rats | Acacia honey (5% or 10%, topical) | Breaking strength was increased. | [95] | |
Wistar rats | Honey (topical) | Wound area was decreased; there were more collagen fibers and fibroblasts in honey-treated group. | [101] | |
Honey + propolis (topical) | Wound area was decreased; number of vessels, collagen, fibroblast and cellular activity were increased. | [102] | ||
Burn wounds | Wistar rats | Honey, milk, and Aloe vera ointment (5%, topical) | Wound area was decreased; thickness of the epidermis, fibroblast, and blood vessel counts were increased; scar tissue was softer. | [103] |
Swiss Wistar rats | Acacia honey (5% or 10%, topical) | Period of epithelialization was reduced; wound contraction was increased. | [95] | |
Guinea pigs | Ulmo (Eucryphia cordifolia) honey (topical) | Eschar was shed earlier and diameter of wound was smaller at day 6–7; diameter of wound decreased to 50% at day 10; no epidermal regeneration was observed; an initial proliferative stage was observed with abundant cellularity, active fibroblasts and neoformation of blood vessels in the superficial dermis. | [104] | |
Ulmo (Eucryphia cordifolia) honey + ascorbic acid (topical) | Eschar was shed earlier and diameter of wound was smaller at day 6; diameter of wound decreased to 50% at day 10; epidermis was generated; an advanced proliferative stage was observed with numerous blood vessels and small capillaries in the superficial dermis, the scar tissue zone presented a fibroblastic reaction, proliferation of collagen fibers, dense connective tissue, and thin collagen fibers. | |||
Burn wounds inoculated with P. aeruginosa, K. pneumonia, or A. baumannii | Sprague-Dawley rats | Tualang honey (0.1 mL/cm2, topical) | Wound size and bacterial count were reduced in P. aeruginosa-inoculated wounds; wounds healed completely on day 21 in P. aeruginosa- and A. baumannii-inoculated groups; no statistically significant anti-bacterial effects in K. pneumonia-infected wounds. | [73,105] |
Wound Type | Animal Type | Intervention: Species, Route | Findings | Study |
---|---|---|---|---|
Excisional wounds | Female Sprague Dawley rats | Total sulphated glycosaminoglycan from S. hermanni and S. Vastus, topical | The contraction rate of wounds treated with total glycosaminoglycan from S. hermanni and S. Vastus showed significant (p < 0.05) improvement compared to control group | [124] |
Either gender of Albino Wistar rats | S. horrens processed oil extract twice daily for consecutive 21 days, topical | At day 4, S. horrens treated group exhibited significantly smaller wounds compared to the negative control (p < 0.001) On days 8, 12, 16 and 21; S. horrens treated group and controls showed no significant change in the wound contraction. | [125] | |
Male Sprague Dawley rats | S. chloronotus at 0.1%, 0.5%, and 1.0% w/w mixed with emulsifying ointment once a day for 10 days, topical | S. chloronotus treated group demonstrated a reduction in wound more rapidly compared to other groups starting on day 6. On the 6th post-wound day, S. chloronotus 0.5% demonstrated a significant wound reduction compared to all other groups (p < 0.05). | [126] | |
Burn wounds | Male Sprague-Dawley rats | S. hermanii Hydrogel dressing followed by OpSite® film dressing as secondary dressing, Topical | At days 7, 14; No significant differences were observed in the measurement of wound contraction between all experimental groups. At days 21, 28; gamat hydrogel significantly increased wound contraction rates. The mRNA levels for pro-inflammatory cytokines (IL-1a, IL-1b, and IL-6) in wounds treated with gamat hydrogel were maintained at low levels throughout the healing process as compared to other groups. Histologically, advanced healing was observed; early re-epithelialization with proliferating and migrating keratinocytes projected toward the center of the wound. | [127] |
Heat-burn wound inoculated with MRSA | Male Sprague-Dawley rats | 30 μg/mL S. badionotus methanol extract applied topically twice daily. | The wound reduction measurement of S. badionotus showed no significant different with vancomycin. | [133] |
Traumatic ulcer induced with heated burnisher | Male Wistar rats. | 20%, 40% and 80% of S. hermanii prepared as gel with polyethylene glycol (PEG) 400 and 4000 solvent, applied one time to ulcer (0.1 mg) | 40% S. hermanii treated group showed the biggest number of lymphocytes, while the 80% S. hermanii extract showed decreased number of lymphocytes. | [134] |
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Ibrahim, N.‘I.; Wong, S.K.; Mohamed, I.N.; Mohamed, N.; Chin, K.-Y.; Ima-Nirwana, S.; Shuid, A.N. Wound Healing Properties of Selected Natural Products. Int. J. Environ. Res. Public Health 2018, 15, 2360. https://doi.org/10.3390/ijerph15112360
Ibrahim N‘I, Wong SK, Mohamed IN, Mohamed N, Chin K-Y, Ima-Nirwana S, Shuid AN. Wound Healing Properties of Selected Natural Products. International Journal of Environmental Research and Public Health. 2018; 15(11):2360. https://doi.org/10.3390/ijerph15112360
Chicago/Turabian StyleIbrahim, Nurul ‘Izzah, Sok Kuan Wong, Isa Naina Mohamed, Norazlina Mohamed, Kok-Yong Chin, Soelaiman Ima-Nirwana, and Ahmad Nazrun Shuid. 2018. "Wound Healing Properties of Selected Natural Products" International Journal of Environmental Research and Public Health 15, no. 11: 2360. https://doi.org/10.3390/ijerph15112360