What Nutrient Repairs Injured Cells
Int J Mol Sci. 2022 Mar; twenty(5): 1119.
Nutrition and Wound Healing: An Overview Focusing on the Beneficial Effects of Curcumin
Giuseppe Evola
2Full general and Emergency Surgery Department, Garibaldi Hospital, Piazza Santa Maria di Gesù, 95100 Catania, Italian republic; ti.liamtoh@alove_eppesuig
Guido Basile
3Department of Full general Surgery and Medical-Surgical Specialties, University of Catania, Via Plebiscito 628, 95124 Catania, Italy; ti.tcinu@elisabg
Received 2022 Jan 25; Accepted 2022 Mar 1.
Abstract
Wound healing implicates several biological and molecular events, such as coagulation, inflammation, migration-proliferation, and remodeling. Hither, nosotros provide an overview of the effects of malnutrition and specific nutrients on this process, focusing on the beneficial furnishings of curcumin. We take summarized that protein loss may negatively affect the whole allowed process, while adequate intake of carbohydrates is necessary for fibroblast migration during the proliferative phase. Beyond micronutrients, arginine and glutamine, vitamin A, B, C, and D, zinc, and iron are essential for inflammatory process and synthesis of collagen. Notably, anti-inflammatory and antioxidant backdrop of curcumin might reduce the expression of tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1) and restore the imbalance between reactive oxygen species (ROS) product and antioxidant action. Since curcumin induces apoptosis of inflammatory cells during the early phase of wound healing, information technology could also accelerate the healing process by shortening the inflammatory phase. Moreover, curcumin might facilitate collagen synthesis, fibroblasts migration, and differentiation. Although curcumin could exist considered as a wound healing agent, specially if topically administered, further enquiry in wound patients is recommended to accomplish appropriate nutritional approaches for wound direction.
Keywords: wound, wound healing, nutrition, diet, micronutrients, macronutrients, curcumin, amino-acids, vitamins, minerals
1. Introduction
Wound healing implicates a well-orchestrated complex of biological and molecular events that involve prison cell migration, jail cell proliferation, and extracellular matrix deposition. Although these processes are similar to those driving embryogenesis, tissue and organ regeneration, and fifty-fifty pathological conditions [one,2], certain differences exist betwixt adult wounds and these other systems. In acute wounds—cutaneous injuries that do not accept an underpinning pathophysiological defect—the main evolutionary force may have been to attain repair chop-chop and with the smallest corporeality of free energy [2]. In contrast, evolutionary adaptations have probably non occurred in chronic wounds with pre-existing pathophysiological abnormalities, resulting in impaired healing [3]. Wound care places an enormous drain on healthcare resources worldwide. For example, in the U.s., it has been estimated that three% individuals over 65 years will have a wound at any i time [four], with an estimated price to the healthcare system of approximately U.s.a. $25 billion each yr [5]. In low-income countries, an even college incidence, due to traumatic injuries and ulcers, is expected. Recently, the World Wellness Arrangement (WHO) has recognized the unmet need for an interdisciplinary approach facing this global challenge, which has been appropriately addressed by the Association for the Advancement of Wound Care (AAWC) Global Volunteers program [half dozen].
Despite strides in technological innovations of a broad range of treatments confronting wounds, non-healing wounds keep to challenge physicians. Hence, further efforts are needed to better our scientific understanding of the repair process and how that noesis can exist used to develop new approaches to handling. Malnutrition is a common adventure gene that might contribute to impaired wound healing [seven,8,9]. In contempo years, several lines of bear witness have pointed out biochemical and molecular furnishings of several nutrients in the wound healing process, supporting the notion that a complementary nutritional approach might be useful in wound handling, specially for chronic not-healing wounds [10]. Hither, we provide an overview of biological and molecular events in wound healing and the effects of malnutrition and specific nutrients on this procedure (search strategy and choice criteria are shown in Figure one). In line with the current Special Issue "Curcumin in Wellness and Affliction", nosotros have also focused on beneficial furnishings and related molecular mechanisms of curcumin—a natural phenol from the rhizome of Curcuma longa—which might heighten healing processes via antioxidant and anti-inflammatory backdrop [11]. In fact, curcumin was commonly used in traditional medicine for the treatment of biliary and hepatic disorders, coughing, diabetic ulcers, rheumatism and sinusitis [11]. More than recently, curcumin has been investigated extensively as an anti-cancer [12], anti-aging [13], and wound healing amanuensis [11]. For instance, it has been demonstrated the beneficial result of curcumin on the progression of endometriosis, a common disorder affecting women during reproductive age which shares some molecular events with wound healing (i.east., adhesion and proliferation, cellular invasion and angiogenesis) [14]. To date, most of the electric current knowledge on wound healing derives from in vitro and in vivo studies, while epidemiological investigations are scarce. To solve the question of whether curcumin is a suitable wound healing amanuensis, we take summarized its biochemical and molecular effects during the different phases of wound healing, equally well every bit evidence from epidemiological studies.
Search strategy and pick criteria.
1.1. The Wound Healing Process and Impaired Healing
The blazon, size, and depth of wounds accept meaning repercussions on cellular and molecular events that occur subsequently cutaneous injury. As reviewed by Falanga [15], information technology is useful to divide the wound healing procedure into 4 overlapping steps of coagulation, inflammation, migration-proliferation, and remodeling (Figure 2). While acute wounds show a linear progression of these overlapping events, the progression in chronic wounds does not occur in synchrony, with some areas beingness in different phases at the same time [fifteen].
Phases and specific events of the wound healing process.
In the first phase afterward injury, the formation of a fibrin plug (i.e., an aggregate of platelets, fibrinogen, fibronectin, vitronectin, and thrombospondin) is necessary both for hemostasis and for covering and protecting the wound from bacteria [2,sixteen]. Beyond that, fibrin plug too provides an extracellular matrix for prison cell migration [2] and releases growth factors (e.1000., platelet-derived growth gene—PDGF—and transforming growth factor—TGF) involved in the recruitment of cells to the wound [1,ii]. In the inflammatory phase, endothelial expression of selectins slows down leukocytes in the bloodstream, and then as to enable them to motility through endothelial gaps by binding to integrins into the extracellular area [1]. Neutrophils and macrophages recruited to the wound remove strange particles and produce a wide range of growth factors and cytokines that promote fibroblast migration and proliferation [17]. Hypoxia—which occurs immediately after injury—is one of the chief triggers of keratinocyte migration, angiogenesis, fibroblast proliferation, and the releasing of growth factors and cytokines (i.e., PDGF, vascular endothelial growth factor, and TGF) [18]. Later on, fibroblasts and endothelial cells course the early granulation tissue that begins the processes of wound contraction, which in turn is an efficient driver of wound closure [2]. Extracellular matrix proteins are crucial in this phase because they provide substrates for cell migration and structures that restore the function and integrity of the tissue [18]. The formation of new blood vessels re-establishes tissue perfusion, allowing for the re-supply of oxygen and other nutrients [17]. Finally, once closure of wound has been achieved, remodeling of the resulting scar takes places over weeks or months, with a reduction of both cell content and blood flow, degradation of extracellular matrix, and further contraction and tensile strength [xv].
While venous or arterial insufficiency, diabetes, and local-pressure are the most common pathophysiological causes of wounds and ulcers, several local and systemic factors can impair wound healing. The first ones consist of the presence of strange bodies, tissue maceration, ischemia, and infection. The second ones include aging, malnutrition, diabetes, and renal diseases. In improver to these factors, a reduction in active growth factors may partially explicate why certain wounds neglect to heal. Chronic ulcers seem to take reduced levels of PDGF, TGF, and other growth factors than astute wounds [xix]. Plausible explanations are that growth factors might be trapped by the extracellular matrix [20] or that they might be excessively degraded by proteases [21]. Moreover, in chronic wounds, fibroblasts show a decreased potential of proliferation accompanied by an increased number of senescent cells that might impair responsiveness to growth hormones [22].
ane.2. Malnutrition, Macronutrients, and Chronic Wounds
According to the WHO, malnutrition refers to all forms of deficiency, excess, or imbalance in a person's intake of free energy and/or nutrients [23]. In old people—who are at the highest hazard of chronic wounds also due to coexisting diseases—malnutrition often consists of either protein-energy malnutrition or specific vitamin and mineral deficiencies [eight]. Several age-related weather condition increase the risk of developing nutritional deficiencies, such as clinical, physiological, and socio-economic difficulties that usually touch the elderly [8]. Particularly, in diabetic patients, college glucose levels could interfere with the process of nutrient absorption, causing the depletion of several nutrients (i.east., magnesium, zinc, B12, B6, folic acrid) [24]. While the response to an injury may increase the metabolic needs of the wound surface area, large amounts of protein can be continually lost through wound exudates [25]. Hence, protein and energy requirements of chronic wound patients may rise by 250% and 50%, respectively [26]. Since cells involved in wound healing require proteins for their germination and action, protein loss may negatively touch on the whole immune process. Proteins are also necessary for immune response, which in turn, if impaired, may filibuster the progression from the inflammatory to the proliferative stage. In the proliferative and remodeling phases, protein-energy deficiency may besides decrease fibroblast action, delaying angiogenesis and reducing collagen germination [8]. Moreover, protein-calorie deficiency is also associated with weight loss and decreased lean body mass [27]. Hence, implications of weight loss and decreased lean torso mass should exist recognized when considering the consequence of protein-calorie deficiency on the healing process. In general, losing ≈10% lean mass is associated with impaired immunity and increased risk of infection. In case patients lose more 10% lean trunk mass, wound healing competes with body demands to restore lean mass: The metabolism gives priority to healing in patients who lose upwardly to 20%, while information technology delays healing to restore lean body mass in those who lose more than than 30% [25,28].
Beyond proteins, both carbohydrates and fats accost increased energy needs to support inflammatory response, cellular activeness, angiogenesis, and collagen deposition in the proliferative phase of healing process [26]. Specially, adequate intake of carbohydrates is necessary for fibroblast production and motility, and leukocyte activity [29]. Carbohydrates also stimulate secretion of hormones and growth factors, including insulin that is helpful in the anabolic processes of the proliferative phase. In contrast, hyperglycemia and its complications might reduce granulocyte role and promote wound germination [7]. Fats take structural functions in the lipid bilayer of cell membranes during tissue growth. They are also precursors of prostaglandins—which in turn are mediators of cellular inflammation and metabolism—and participate in several signaling pathways [xxx]. To engagement, the effect of supplementation of essential fatty acids on wound healing is controversial. While omega-3 supplementation might decrease wound tensile strength with a harmful effect on healing [31], its combination with omega-6 decreases the progression of pressure ulcers [32]. In line with this show, the co-supplementation of omega-three and omega-vi might atomic number 82 to benefits, especially during the inflammatory phase [33].
1.three. Micronutrients and Wound Healing
i.iii.ane. Amino-Acids
Micronutrients involved in the wound healing process have been extensively reviewed [vii,8,9,33]. Amongst amino-acids, those that play an important function in wound healing, are arginine and glutamine. The first is a forerunner of nitric oxide and proline, which in plough are essential for the inflammatory procedure [34] and synthesis of collagen [35,36]. Arginine also stimulates the production and secretion of growth hormone, besides as the activation of T cells [37,38]. In wound patients with acceptable poly peptide intake, the recommended dose of arginine supplementation is iv.5 g/24-hour interval, while information technology is useless in the context of protein deficiency [39]. Glutamine plays several roles via its metabolic, enzymatic, antioxidant, and immune backdrop. In wounds, it protects confronting the risk of infectious and inflammatory complications by up-regulating the expression of heat stupor proteins [40]. Glutamine is also a precursor of glutathione—an antioxidant and an essential cofactor of several enzymatic reactions—which is important for stabilizing cell membranes and for transporting amino acids across them [41]. In addition, glutamine seems involved in the inflammatory phase of wound healing by regulating leukocyte apoptosis, superoxide production, antigen processing, and phagocytosis [40,42]. As for arginine, benefits of glutamine supplementation are still controversial [43] and confounded by the combinations of supplements [44].
1.3.two. Vitamins
Vitamins are undoubtedly the nearly investigated micronutrients in the wound healing process. Vitamin A deficiency impairs B cell and T cell office and antibody production during the inflammatory phase. It besides decreases epithelialization, collagen synthesis, and granulation tissue evolution in the proliferative and remodeling phases [45]. In addition, vitamin A seems to work as a hormone that modulates the activeness of epithelial and endothelial cells, melanocytes, and fibroblasts by bounden to retinoic acid receptors [46]. In general, vitamin A is topically administered for the care of dermatologic conditions due to its stimulating backdrop of fibroplasia and epithelialization [33]. In wound patients, it has been recommended to take a brusque-term supplementation of ten,000–25,000 IU/day to avert toxicity [33]. Interestingly, vitamin A supplementation counteracts the delay in wound healing caused by corticosteroids for the handling of inflammatory diseases [47] past down-regulating TGF-β and insulin-like growth factor-1 (IGF-1) [48]. B vitamins, which consist of thiamine, riboflavin, pyridoxine, folic acid, pantothenate, and cobalamins, are essential cofactors in enzyme reactions involved in leukocyte formation and in anabolic processes of wound healing. Among these, thiamine, riboflavin, pyridoxine and cobalamins are as well required for the synthesis of collagen [25]. Hence, vitamin B deficiencies indirectly affect the wound healing process by impairing antibody product and white blood cell function, which in plow increase the risk of infectious complications [49]. Vitamin C seems to be involved in wound healing with several roles in cell migration and transformation, collagen synthesis, antioxidant response, and angiogenesis.
In the inflammatory phase, it participates in the recruitment of cells to the wound and their transformation into macrophages [29]. During collagen synthesis, vitamin C forms extra-bounds between collagen fibers that increase stability and strength of collagen matrix [8]. Vitamin C is essential to counteract the product of free radicals in damaged cells, while its deficiency might increase the fragility of new vessels [50]. The electric current recommendation of vitamin C supplementation ranges from 500 mg/twenty-four hours in non-complicated wounds to two 1000/day in astringent wounds [33]. However, vitamin C supplementation seems to have a beneficial effect only in combination with zinc and arginine, and in force per unit area ulcer patients [51]. Vitamin D and its receptor (i.e., VDR)—which is ubiquitously expressed in several tissues—modulate structural integrity and send across epithelial barriers [52]. In line with its roles, recent evidence of vitamin D deficiency amongst venous and pressure ulcer patients has suggested the potential interest of vitamin D in the wound healing process [53,54]. Notwithstanding, farther research is recommended to understand how vitamin D supplementation might be used in wound care. Although nigh vitamins show beneficial effects in wound healing, vitamin E might negatively bear on collagen synthesis, antioxidant response, and the inflammatory stage [55]. Moreover, vitamin E appears to counteract the benefits of vitamin A supplementation in wound management [56].
1.3.3. Minerals
Several minerals are involved in the wound healing procedure due to their roles as enzyme structural factors, metalloenzymes, and antioxidants. Among these, zinc is essential for DNA replication in cells with high cell segmentation rates, such as inflammatory and epithelial cells, and fibroblasts. In the inflammatory phase, zinc promotes immune response and counteracts susceptibility to infectious complications by activating lymphocytes and producing antibodies [xxx]. In the proliferative and remodeling phases, it is essential for collagen production, fibroblast proliferation, and epithelialization by stimulating the activity of involved enzymes [8]. Although zinc supplementation of 40–220 mg/day for 10–14 days [57] might exist useful in zinc-deficient patients, its benefits in not-deficient patients are currently under debate [9]. Interestingly, topical assistants of zinc to surgical wounds significantly improves the healing process [58]. In contrast, conditions that affect zinc metabolism and potential drug-nutrient interactions should exist considered for the management of wound patients with zinc supplementation [58]. Less show exists on the beneficial furnishings of atomic number 26 supplementation for promoting wound healing. As iron transports oxygen to the tissues, it is essential for tissue perfusion and collagen synthesis. Hence, iron deficiency results in tissue ischemia, dumb collagen product, and decreased wound strength in the proliferative stage [30].
i.4. Curcumin and Wound Healing
In 1910, Milobedzka and colleagues described for the first time the structure of curcumin (Effigy 3), one of the three curcuminoids extracted from the powdered rhizome of turmeric institute (Curcuma longa) [59]. More recently, it has been demonstrated that curcumin might attune physiological and molecular events involved in the inflammatory and proliferative phases of the wound healing procedure [lx].
Structure and effects of curcumin on wound healing.
1.4.1. Effects on the Inflammatory Stage
With respect to the inflammatory phase, several studies have revealed the protective effect of curcumin that reduces the expression of pro-inflammatory cytokines, such every bit tumor necrosis cistron blastoff (TNF-α) and interleukin-ane (IL-one) [61]. Accordingly, curcumin recruits M2-like macrophages into white adipose tissues, thereby increasing the production of anti-inflammatory cytokines that are essential for the inflammatory response [62]. In improver, curcumin also inhibits nuclear gene κB (NF-κB) by suppressing the activity of kinases (i.e., AKT, PI3K, IKK) involved in several pathways. In general, NF-κB is physiologically inactivated by binding to its inhibitor IκB. During inflammation, the up-regulation of inflammatory mediators (i.due east., cytokines and chemokines) activates NF-κB, which in plough translocates to the nucleus [63]. In wounded sites, curcumin might reduce inflammation acquired by the activation of the NF-κB pathway [64]. The anti-inflammatory effects of curcumin are as well involved in other signaling pathways, such equally peroxisome proliferator-activated receptor-gamma (PPAR-γ) and myeloid differentiation poly peptide two-TLR 4 co-receptor (TLR4-MD2) [65,66,67,68]. Li and colleagues have reported that curcumin suppresses proliferation of vascular smooth muscle cells by increasing PPAR-γ activity to mitigate angiotensin II-induced inflammatory responses [67]. Additionally, it has been shown that curcumin reduces inflammation through competition with LPS for binding on MD2, thereby inhibiting the TLR4-MD2 signaling complex [68].
Since NF-κB has likewise several anti-oxidant targets, in 2004, Frey and Malik proposed a human relationship between inflammation and oxidation during the wound healing process [69]. In wounds, ROS germination triggers the production and activeness of various immune cells (i.eastward., T lymphocyte subsets, macrophages, dendritic cells, B lymphocytes, and natural killer cells). Moreover, prolonged loftier ROS concentrations are dangerous for jail cell structures leading to oxidative stress [seventy,71]. Particularly, hydrogen peroxide (HiiO2) and superoxide (Otwo −) can be considered every bit potential markers for the corporeality of oxidative stress [72]. Although anti-oxidant enzymes (i.e., superoxide dismutase, glutathione peroxidase, and catalase) protect cells against toxic ROS levels [73], the imbalance between ROS concentrations and antioxidant activity could determine chronic diseases. Beyond its anti-inflammatory properties, curcumin too acts as an antioxidant by scavenging ROS, by restoring aberrant changes induced past external factors, and by suppressing transcription factors related to oxidation [74,75]. In vitro and in vivo studies have demonstrated the antioxidant activities of curcumin conferred by its electron-altruistic groups (i.e., the phenolic hydroxyl group) [76]. Moreover, it contributes to the production and activity of antioxidant enzymes [77,78] and their constituents, such equally glutathione (GSH) [79]. In line with these findings, Phan and colleagues have revealed the protective office of curcumin against hydrogen peroxide in keratinocytes and fibroblasts [80].
1.4.2. Effects on the Proliferative and Remodeling Phases
As discussed below, curcumin besides plays a critical part during the proliferative phase. Interestingly, Gopinath and colleagues have observed that curcumin ameliorates the higher up-mentioned process, resulting in an increase of hydroxyproline and collagen synthesis [74]. This is consistent with previous studies demonstrating that curcumin decreases the amount of membrane matrix metallo-proteinases (MMPs), which are usually higher in endometriotic mice and human ovarian endometriotic stromal cells. These pathological atmospheric condition, in fact, share some molecular events with wound healing, including adhesion and proliferation, cellular invasion, and angiogenesis. Especially, curcumin could be involved in the process of endometriosis past decreasing the growth and number of endometriotic stromal cells [81]. With respect to wounds, Panchatcharam and colleagues have demonstrated that collagen fibers could mature before when wound rats are topically treated with curcumin [lxx]. Although curcumin does non seem to be involved in the migration of fibroblasts to the wound area in vitro [17], an in vivo study has suggested that curcumin mediates the infiltration of fibroblasts into wound sites, which in turn naturally differentiates into myofibroblasts during the formation of granulation tissue [82]. This controversy might be due to difficulties in creating an in vitro model of fibroblast migration in wounds. Treatment with curcumin likewise promotes the differentiation of fibroblasts into myofibroblasts [83,84,85,86] which marks the kickoff of wound contraction [87]. A previous report has likewise demonstrated that curcumin reduces the epithelialization menstruation of treated wounds if compared with the control group [70]. Finally, once closure of the wound has been achieved, apoptotic processes discard inflammatory cells from wound sites [88,89,90]. Since curcumin induces apoptosis during the early on phase of wound healing, it could also accelerate the healing procedure past shortening the inflammatory stage [85].
ii. Word
Our review summarizes current bear witness about the master biochemical and molecular effects of nutrition, in terms of quality and quantity, on the wound healing process. In line with the Special Consequence "Curcumin in Health and Disease", we have focused on the beneficial effects of curcumin, which exerts its anti-inflammatory and antioxidant backdrop during the different phases of the wound healing process [11]. Several lines of evidence from in vitro and in vivo studies take reported that curcumin might modulate physiological and molecular events during the inflammatory stage [60,61,65,66,67,68,85]. Moreover, information technology as well exerts antioxidant effects by restoring the imbalance between ROS production and antioxidant activity [74,75,76,77,78,79,fourscore]. In the proliferative phase, curcumin might facilitate collagen synthesis [70,74], fibroblasts migration [82], and differentiation [83,84,85,86]. In addition, curcumin appears to be benign for epithelialization [70] and for apoptotic processes that discard inflammatory cells from the wound site [88,89,90]. An in vivo study has suggested that curcumin mediates the infiltration of fibroblasts into wound sites, which in turn naturally differentiates into myofibroblasts during the formation of granulation tissue [82]. By contrast, curcumin does non seem to be involved in the migration of fibroblasts to the wound area in vitro [17].
This controversy might be due to difficulties in creating an in vitro model of fibroblast migration in wounds. In fact, fibroblast migration depends on several factors that cannot be entirely mimicked with in vitro models, such as cell-environment interactions and homeostatic mechanisms [17]. Recently, in wounds of diabetic rats, it has been demonstrated that topical curcumin handling enhances angiogenesis, thereby ameliorating the healing process [91]. In line with these findings, curcumin could exist considered an interesting phytochemical candidate for the treatment of non-healing wounds. Interestingly, its pleiotropic effect on several signaling pathways—past modulating cellular regulatory systems, such every bit NF-κB, AKT, growth factors, and Nrf2 transcription cistron [92,93,94,95]—might exist explained past its well-established part in epigenetic mechanisms, such every bit Deoxyribonucleic acid methylation and histone modification [96]. An understanding of epigenetic regulation in the wound healing process is at present becoming an bonny field of research [97], and more efforts should be made to uncover mechanisms underpinning benign furnishings of curcumin and other polyphenols [96,98]. As mentioned above, however, most of these findings come from in vitro or in vivo investigations, while evidence from epidemiological studies is scarce. Given its hydrophobicity and all-encompassing first-laissez passer metabolism [99,100], topical administration of curcumin has a greater effect on wound healing than oral administration [64,88,89]. Despite strides which have been made in the formulation of curcumin for topical application at the wound site [74,83,84,85,101], further research is recommended to amend curcumin delivery and to evaluate its effects in wound patients.
Across assessing the potential of curcumin every bit a wound healing agent, nosotros have too indicated that nutritional assessment in patients at risk of chronic wounds could be the first stride towards the prevention of non-healing wounds. In fact, these patients often exhibit protein-energy malnutrition or specific vitamin and mineral deficiencies [8]. The wound healing process, for its part, increases the needs of calories and proteins of the wound area, thereby increasing the requirements from chronic wound patients [26]. Given that poly peptide-calorie deficiencies are further associated with weight loss and decreased lean trunk mass [27], their implications for wound patients should be also recognized. To meet the increased need of energy, especially during the proliferative phase, wounds also metabolize carbohydrates and fats [26], which in turn are necessary for fibroblast and leukocyte activities, secretion of hormones and growth factors, and structural functions [29,xxx]. Despite this bear witness, the upshot of macronutrient supplementation is currently controversial, raising the need for farther inquiry. For instance, it has been demonstrated that omega-6 supplementation decreases the progression of pressure ulcers [32], and its combination with omega-3 has beneficial effects on the inflammatory stage [33]. However, omega-3 supplementation alone has harmful effects on healing [31].
Across macronutrients, several micronutrients play a crucial role in the wound healing process, as extensively reviewed [7,8,9,33]. Arginine and glutamine exhibit several metabolic, enzymatic, antioxidant, and anti-inflammatory backdrop that are involved in the inflammatory phase [34,37,38,40,42] and in collagen synthesis [35,36]. However, the beneficial effect of the supplementation of glutamine and arginine, lonely or in combination, is nonetheless controversial [43,44], probably due to differences in study design, patient characteristics, and type of supplementation. Nearly of the evidence comes from research on vitamins, with several lines of evidence supporting the benefits of vitamin A [33,47,48], vitamin B [49], vitamin C [viii,29,50] and vitamin D [53,54] supplementation. Notwithstanding, to what extent they support wound healing procedure remains unclear until at present. For instance, vitamin C seems to human activity only in combination with zinc and arginine [51], while vitamin E appears to counteract the benefits of vitamin A [56]. Amidst minerals, zinc is essential for the inflammatory, proliferative, and remodeling phases by promoting immune response, collagen production, fibroblast proliferation, and epithelialization [8]. Appropriately, topical zinc administration to surgical wounds significantly facilitates wound healing process [58]. These findings cumulatively suggest that nutritional approaches might be useful in the treatment of wounds, especially of chronic non-healing wounds [10]. Even so, benefits in not-deficient patients are currently under contend [9], and further research should have into business relationship atmospheric condition that affect nutrient metabolism, such as diabetes and potential food–nutrient interactions [58].
three. Conclusions
In determination, nosotros back up the notion that curcumin could be considered as a wound healing agent, especially if topically administered. Still, near of the current knowledge is derived from in vitro and in vivo investigations, while studies in wound patients remain scarce or controversial. Moreover, since nutrition and nutrients in general might affect the wound healing process, nutritional cess of patients at risk of non-healing wounds could be the outset pace towards prevention and treatment. However, further enquiry is recommended to develop advisable nutritional approaches for wound management.
Abbreviations
| AAWC | Advancement of Wound Intendance |
| GSH | Glutathione |
| H2Oii | Hydrogen Peroxide |
| IGF-1 | Insulin-Like Growth Factor-1 |
| IL-1 | Interleukin-one |
| NF-κB | Nuclear Factor κB |
| Oii − | Hydrogen Superoxide |
| PDGF | Platelet-Derived Growth Factor |
| PPAR-γ | Peroxisome Proliferator-Activated Receptor-Gamma |
| ROS | Reactive Oxygen Species |
| TGF | Transforming Growth Gene |
| TLR4-MD2 | Myeloid Differentiation Protein 2-TLR four Co-Receptor |
| TNF-α | Tumor Necrosis Factor Blastoff |
| VDR | Vitamin D Receptor |
| WHO | Earth Health Organization |
Author Contributions
Conceptualization, A.Chiliad., Thousand.B., A.A. and Grand.B.; methodology, A.M. and Chiliad.B.; writing—original draft preparation, A.M., One thousand.F., R.M.S.50., 1000.Eastward., and A.A.; writing—review and editing, all the authors.
Funding
This inquiry was partially funded past the Department of Medical and Surgical Sciences and Advanced Technologies "GF Ingrassia", Academy of Catania, Catania, Italy.
Conflicts of Interest
The authors declare no disharmonize of interest.
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What Nutrient Repairs Injured Cells,
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