Wound Healing Internal Ground Beef Inflammation
Int J Mol Sci. 2019 Mar; 20(5): 1119.
Nutrition and Wound Healing: An Overview Focusing on the Beneficial Effects of Curcumin
Giuseppe Evola
twoFull general and Emergency Surgery Department, Garibaldi Hospital, Piazza Santa Maria di Gesù, 95100 Catania, Italian republic; ti.liamtoh@alove_eppesuig
Guido Basile
3Department of General Surgery and Medical-Surgical Specialties, University of Catania, Via Plebiscito 628, 95124 Catania, Italy; ti.tcinu@elisabg
Received 2019 Jan 25; Accepted 2019 Mar 1.
Abstruse
Wound healing implicates several biological and molecular events, such as coagulation, inflammation, migration-proliferation, and remodeling. Here, we provide an overview of the furnishings of malnutrition and specific nutrients on this procedure, focusing on the beneficial effects of curcumin. We have summarized that protein loss may negatively affect the whole immune 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 fe are essential for inflammatory process and synthesis of collagen. Notably, anti-inflammatory and antioxidant properties of curcumin might reduce the expression of tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-ane) and restore the imbalance between reactive oxygen species (ROS) production and antioxidant activity. Since curcumin induces apoptosis of inflammatory cells during the early phase of wound healing, information technology could besides accelerate the healing procedure by shortening the inflammatory phase. Moreover, curcumin might facilitate collagen synthesis, fibroblasts migration, and differentiation. Although curcumin could be considered every bit a wound healing agent, especially if topically administered, farther inquiry in wound patients is recommended to accomplish appropriate nutritional approaches for wound management.
Keywords: wound, wound healing, diet, nutrition, micronutrients, macronutrients, curcumin, amino-acids, vitamins, minerals
one. Introduction
Wound healing implicates a well-orchestrated complex of biological and molecular events that involve jail cell migration, prison cell proliferation, and extracellular matrix deposition. Although these processes are similar to those driving embryogenesis, tissue and organ regeneration, and even pathological weather condition [1,2], sure differences exist between adult wounds and these other systems. In acute wounds—cutaneous injuries that do not have an underpinning pathophysiological defect—the master evolutionary forcefulness may have been to achieve repair quickly and with the smallest corporeality of energy [2]. In dissimilarity, evolutionary adaptations have probably not occurred in chronic wounds with pre-existing pathophysiological abnormalities, resulting in impaired healing [3]. Wound care places an enormous drain on healthcare resource worldwide. For instance, in the United States, it has been estimated that 3% individuals over 65 years will take a wound at any i time [4], with an estimated cost to the healthcare system of approximately US $25 billion each year [5]. In depression-income countries, an even college incidence, due to traumatic injuries and ulcers, is expected. Recently, the World Health Organization (WHO) has recognized the unmet need for an interdisciplinary approach facing this global challenge, which has been appropriately addressed by the Association for the Advocacy of Wound Care (AAWC) Global Volunteers program [vi].
Despite strides in technological innovations of a wide range of treatments against wounds, not-healing wounds go along to challenge physicians. Hence, further efforts are needed to improve our scientific understanding of the repair process and how that cognition can be used to develop new approaches to handling. Malnutrition is a common risk gene that might contribute to impaired wound healing [7,eight,9]. In recent years, several lines of show have pointed out biochemical and molecular effects of several nutrients in the wound healing process, supporting the notion that a complementary nutritional approach might be useful in wound treatment, particularly for chronic non-healing wounds [ten]. Here, we provide an overview of biological and molecular events in wound healing and the effects of malnutrition and specific nutrients on this process (search strategy and selection criteria are shown in Effigy 1). In line with the electric current Special Issue "Curcumin in Health and Disease", we take also focused on benign furnishings and related molecular mechanisms of curcumin—a natural phenol from the rhizome of Curcuma longa—which might raise healing processes via antioxidant and anti-inflammatory backdrop [eleven]. In fact, curcumin was unremarkably used in traditional medicine for the treatment of biliary and hepatic disorders, cough, diabetic ulcers, rheumatism and sinusitis [eleven]. More recently, curcumin has been investigated extensively as an anti-cancer [12], anti-aging [thirteen], and wound healing agent [11]. For case, information technology has been demonstrated the beneficial effect of curcumin on the progression of endometriosis, a common disorder affecting women during reproductive age which shares some molecular events with wound healing (i.eastward., adhesion and proliferation, cellular invasion and angiogenesis) [14]. To date, most of the current cognition 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 agent, we take summarized its biochemical and molecular effects during the different phases of wound healing, likewise as testify from epidemiological studies.
Search strategy and selection criteria.
one.1. The Wound Healing Process and Impaired Healing
The blazon, size, and depth of wounds have significant repercussions on cellular and molecular events that occur after cutaneous injury. As reviewed past Falanga [fifteen], it is useful to separate the wound healing process into four overlapping steps of coagulation, inflammation, migration-proliferation, and remodeling (Figure ii). While acute wounds show a linear progression of these overlapping events, the progression in chronic wounds does not occur in synchrony, with some areas being in unlike phases at the same time [xv].
Phases and specific events of the wound healing procedure.
In the first phase afterward injury, the germination of a fibrin plug (i.east., 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 also provides an extracellular matrix for prison cell migration [two] and releases growth factors (e.g., platelet-derived growth gene—PDGF—and transforming growth factor—TGF) involved in the recruitment of cells to the wound [one,2]. In the inflammatory phase, endothelial expression of selectins slows down leukocytes in the bloodstream, so every bit to enable them to motility through endothelial gaps by binding to integrins into the extracellular surface area [1]. Neutrophils and macrophages recruited to the wound remove foreign particles and produce a wide range of growth factors and cytokines that promote fibroblast migration and proliferation [17]. Hypoxia—which occurs immediately afterwards injury—is i of the primary triggers of keratinocyte migration, angiogenesis, fibroblast proliferation, and the releasing of growth factors and cytokines (i.eastward., PDGF, vascular endothelial growth factor, and TGF) [18]. Later, fibroblasts and endothelial cells form the early granulation tissue that begins the processes of wound contraction, which in turn is an efficient driver of wound closure [ii]. Extracellular matrix proteins are crucial in this phase considering they provide substrates for prison cell migration and structures that restore the office and integrity of the tissue [18]. The germination 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 accomplished, remodeling of the resulting scar takes places over weeks or months, with a reduction of both prison cell content and claret menses, degradation of extracellular matrix, and further contraction and tensile force [15].
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 start ones consist of the presence of foreign bodies, tissue maceration, ischemia, and infection. The 2nd ones include aging, malnutrition, diabetes, and renal diseases. In addition to these factors, a reduction in active growth factors may partially explain why certain wounds fail to heal. Chronic ulcers seem to take reduced levels of PDGF, TGF, and other growth factors than astute wounds [19]. 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].
1.2. Malnutrition, Macronutrients, and Chronic Wounds
Co-ordinate 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 quondam people—who are at the highest risk of chronic wounds also due to coexisting diseases—malnutrition oftentimes consists of either poly peptide-energy malnutrition or specific vitamin and mineral deficiencies [8]. Several historic period-related weather condition increase the run a risk of developing nutritional deficiencies, such as clinical, physiological, and socio-economic difficulties that usually affect the elderly [8]. Particularly, in diabetic patients, higher glucose levels could interfere with the process of nutrient absorption, causing the depletion of several nutrients (i.e., magnesium, zinc, B12, B6, folic acid) [24]. While the response to an injury may increment the metabolic needs of the wound area, big amounts of protein tin can exist continually lost through wound exudates [25]. Hence, poly peptide and energy requirements of chronic wound patients may ascent by 250% and 50%, respectively [26]. Since cells involved in wound healing require proteins for their germination and activity, protein loss may negatively affect the whole allowed process. Proteins are also necessary for allowed response, which in turn, if impaired, may delay the progression from the inflammatory to the proliferative stage. In the proliferative and remodeling phases, protein-energy deficiency may also decrease fibroblast activity, 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 effect of poly peptide-calorie deficiency on the healing process. In full general, losing ≈10% lean mass is associated with dumb immunity and increased take a chance of infection. In case patients lose more than 10% lean body mass, wound healing competes with body demands to restore lean mass: The metabolism gives priority to healing in patients who lose up to 20%, while it delays healing to restore lean body mass in those who lose more than xxx% [25,28].
Across proteins, both carbohydrates and fats address increased free energy needs to support inflammatory response, cellular activity, angiogenesis, and collagen degradation in the proliferative phase of healing process [26]. Particularly, adequate intake of carbohydrates is necessary for fibroblast production and movement, 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 function and promote wound formation [7]. Fats have structural functions in the lipid bilayer of cell membranes during tissue growth. They are likewise precursors of prostaglandins—which in plow are mediators of cellular inflammation and metabolism—and participate in several signaling pathways [30]. To date, the effect of supplementation of essential fatty acids on wound healing is controversial. While omega-three supplementation might decrease wound tensile strength with a harmful result on healing [31], its combination with omega-half dozen decreases the progression of force per unit area ulcers [32]. In line with this show, the co-supplementation of omega-3 and omega-6 might lead to benefits, particularly during the inflammatory phase [33].
1.three. Micronutrients and Wound Healing
1.3.1. Amino-Acids
Micronutrients involved in the wound healing process accept been extensively reviewed [7,viii,9,33]. Among amino-acids, those that play an important office in wound healing, are arginine and glutamine. The commencement is a forerunner of nitric oxide and proline, which in turn are essential for the inflammatory procedure [34] and synthesis of collagen [35,36]. Arginine too stimulates the production and secretion of growth hormone, besides as the activation of T cells [37,38]. In wound patients with adequate protein intake, the recommended dose of arginine supplementation is 4.5 yard/solar day, while it is useless in the context of protein deficiency [39]. Glutamine plays several roles via its metabolic, enzymatic, antioxidant, and immune properties. In wounds, it protects confronting the risk of infectious and inflammatory complications past up-regulating the expression of heat stupor proteins [xl]. Glutamine is also a precursor of glutathione—an antioxidant and an essential cofactor of several enzymatic reactions—which is important for stabilizing prison 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]. Equally for arginine, benefits of glutamine supplementation are still controversial [43] and confounded by the combinations of supplements [44].
1.3.2. Vitamins
Vitamins are undoubtedly the most investigated micronutrients in the wound healing process. Vitamin A deficiency impairs B cell and T jail cell role and antibody production during the inflammatory phase. It also decreases epithelialization, collagen synthesis, and granulation tissue evolution in the proliferative and remodeling phases [45]. In addition, vitamin A seems to piece of work equally a hormone that modulates the activity of epithelial and endothelial cells, melanocytes, and fibroblasts by binding to retinoic acid receptors [46]. In general, vitamin A is topically administered for the intendance of dermatologic conditions due to its stimulating properties of fibroplasia and epithelialization [33]. In wound patients, it has been recommended to have a brusk-term supplementation of 10,000–25,000 IU/day to avoid toxicity [33]. Interestingly, vitamin A supplementation counteracts the filibuster in wound healing caused by corticosteroids for the treatment of inflammatory diseases [47] by down-regulating TGF-β and insulin-like growth gene-ane (IGF-one) [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. Amidst these, thiamine, riboflavin, pyridoxine and cobalamins are also required for the synthesis of collagen [25]. Hence, vitamin B deficiencies indirectly affect the wound healing process by impairing antibiotic production and white blood jail cell function, which in plough increment 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 actress-bounds betwixt collagen fibers that increment stability and forcefulness of collagen matrix [8]. Vitamin C is essential to counteract the production of free radicals in damaged cells, while its deficiency might increase the fragility of new vessels [fifty]. The electric current recommendation of vitamin C supplementation ranges from 500 mg/24-hour interval in non-complicated wounds to 2 g/day in severe wounds [33]. However, vitamin C supplementation seems to have a benign result 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 transport across epithelial barriers [52]. In line with its roles, recent evidence of vitamin D deficiency among venous and force per unit area ulcer patients has suggested the potential involvement of vitamin D in the wound healing process [53,54]. However, further research is recommended to understand how vitamin D supplementation might be used in wound care. Although nigh vitamins testify beneficial furnishings in wound healing, vitamin E might negatively affect collagen synthesis, antioxidant response, and the inflammatory phase [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 process due to their roles as enzyme structural factors, metalloenzymes, and antioxidants. Amongst these, zinc is essential for Dna replication in cells with high cell sectionalization rates, such as inflammatory and epithelial cells, and fibroblasts. In the inflammatory phase, zinc promotes allowed response and counteracts susceptibility to infectious complications by activating lymphocytes and producing antibodies [thirty]. In the proliferative and remodeling phases, information technology 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–xiv days [57] might be useful in zinc-deficient patients, its benefits in non-deficient patients are currently nether debate [nine]. Interestingly, topical assistants of zinc to surgical wounds significantly improves the healing process [58]. In dissimilarity, atmospheric condition that touch on zinc metabolism and potential drug-nutrient interactions should be considered for the management of wound patients with zinc supplementation [58]. Less evidence exists on the beneficial effects of iron supplementation for promoting wound healing. Equally iron transports oxygen to the tissues, it is essential for tissue perfusion and collagen synthesis. Hence, iron deficiency results in tissue ischemia, impaired collagen production, and decreased wound strength in the proliferative stage [xxx].
1.4. Curcumin and Wound Healing
In 1910, Milobedzka and colleagues described for the first time the structure of curcumin (Figure 3), i of the three curcuminoids extracted from the powdered rhizome of turmeric plant (Curcuma longa) [59]. More recently, it has been demonstrated that curcumin might modulate physiological and molecular events involved in the inflammatory and proliferative phases of the wound healing process [60].
Structure and effects of curcumin on wound healing.
1.4.i. Furnishings on the Inflammatory Phase
With respect to the inflammatory phase, several studies have revealed the protective outcome of curcumin that reduces the expression of pro-inflammatory cytokines, such as tumor necrosis gene alpha (TNF-α) and interleukin-one (IL-1) [61]. Accordingly, curcumin recruits M2-similar macrophages into white adipose tissues, thereby increasing the production of anti-inflammatory cytokines that are essential for the inflammatory response [62]. In add-on, curcumin likewise inhibits nuclear factor κB (NF-κB) by suppressing the activity of kinases (i.due east., 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.e., cytokines and chemokines) activates NF-κB, which in turn 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 also involved in other signaling pathways, such as 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, information technology 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 also several anti-oxidant targets, in 2004, Frey and Malik proposed a relationship between inflammation and oxidation during the wound healing procedure [69]. In wounds, ROS formation triggers the production and activity of diverse immune cells (i.e., T lymphocyte subsets, macrophages, dendritic cells, B lymphocytes, and natural killer cells). Moreover, prolonged high ROS concentrations are unsafe for prison cell structures leading to oxidative stress [70,71]. Peculiarly, hydrogen peroxide (HiiO2) and superoxide (O2 −) can be considered equally potential markers for the amount of oxidative stress [72]. Although anti-oxidant enzymes (i.eastward., superoxide dismutase, glutathione peroxidase, and catalase) protect cells against toxic ROS levels [73], the imbalance betwixt ROS concentrations and antioxidant action could determine chronic diseases. Across its anti-inflammatory properties, curcumin also acts as an antioxidant by scavenging ROS, by restoring abnormal changes induced by external factors, and by suppressing transcription factors related to oxidation [74,75]. In vitro and in vivo studies accept demonstrated the antioxidant activities of curcumin conferred by its electron-donating groups (i.eastward., the phenolic hydroxyl group) [76]. Moreover, it contributes to the production and action of antioxidant enzymes [77,78] and their constituents, such every bit glutathione (GSH) [79]. In line with these findings, Phan and colleagues have revealed the protective role of curcumin against hydrogen peroxide in keratinocytes and fibroblasts [80].
ane.4.ii. Effects on the Proliferative and Remodeling Phases
As discussed below, curcumin besides plays a critical role during the proliferative phase. Interestingly, Gopinath and colleagues have observed that curcumin ameliorates the above-mentioned procedure, 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 conditions, in fact, share some molecular events with wound healing, including adhesion and proliferation, cellular invasion, and angiogenesis. Particularly, curcumin could be involved in the process of endometriosis by decreasing the growth and number of endometriotic stromal cells [81]. With respect to wounds, Panchatcharam and colleagues take demonstrated that collagen fibers could mature earlier when wound rats are topically treated with curcumin [70]. Although curcumin does not seem to be involved in the migration of fibroblasts to the wound area in vitro [17], an in vivo report has suggested that curcumin mediates the infiltration of fibroblasts into wound sites, which in plough naturally differentiates into myofibroblasts during the formation of granulation tissue [82]. This controversy might exist due to difficulties in creating an in vitro model of fibroblast migration in wounds. Treatment with curcumin as well promotes the differentiation of fibroblasts into myofibroblasts [83,84,85,86] which marks the beginning of wound wrinkle [87]. A previous study has too demonstrated that curcumin reduces the epithelialization catamenia 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,xc]. Since curcumin induces apoptosis during the early phase of wound healing, it could likewise advance the healing process by shortening the inflammatory phase [85].
2. Discussion
Our review summarizes current show nearly the master biochemical and molecular effects of nutrition, in terms of quality and quantity, on the wound healing procedure. In line with the Special Issue "Curcumin in Health and Illness", we have focused on the beneficial furnishings 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, it too exerts antioxidant effects past restoring the imbalance between ROS production and antioxidant activity [74,75,76,77,78,79,80]. 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 beneficial for epithelialization [lxx] 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 germination of granulation tissue [82]. Past contrast, curcumin does not 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-surround interactions and homeostatic mechanisms [17]. Recently, in wounds of diabetic rats, it has been demonstrated that topical curcumin treatment enhances angiogenesis, thereby ameliorating the healing process [91]. In line with these findings, curcumin could be considered an interesting phytochemical candidate for the handling of non-healing wounds. Interestingly, its pleiotropic outcome on several signaling pathways—past modulating cellular regulatory systems, such as NF-κB, AKT, growth factors, and Nrf2 transcription factor [92,93,94,95]—might exist explained past its well-established role in epigenetic mechanisms, such every bit DNA methylation and histone modification [96]. An agreement of epigenetic regulation in the wound healing process is now becoming an attractive field of research [97], and more efforts should be made to uncover mechanisms underpinning beneficial effects of curcumin and other polyphenols [96,98]. Equally mentioned above, notwithstanding, most of these findings come up from in vitro or in vivo investigations, while evidence from epidemiological studies is scarce. Given its hydrophobicity and all-encompassing first-pass metabolism [99,100], topical administration of curcumin has a greater event on wound healing than oral administration [64,88,89]. Despite strides which accept been fabricated in the formulation of curcumin for topical application at the wound site [74,83,84,85,101], further research is recommended to improve curcumin delivery and to evaluate its furnishings in wound patients.
Across assessing the potential of curcumin as a wound healing amanuensis, we accept too indicated that nutritional assessment in patients at risk of chronic wounds could be the get-go 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 procedure, for its function, increases the needs of calories and proteins of the wound area, thereby increasing the requirements from chronic wound patients [26]. Given that protein-calorie deficiencies are further associated with weight loss and decreased lean body mass [27], their implications for wound patients should be also recognized. To run across the increased demand of energy, especially during the proliferative stage, wounds likewise metabolize carbohydrates and fats [26], which in turn are necessary for fibroblast and leukocyte activities, secretion of hormones and growth factors, and structural functions [29,30]. Despite this evidence, the result of macronutrient supplementation is currently controversial, raising the demand for further inquiry. For instance, information technology has been demonstrated that omega-6 supplementation decreases the progression of force per unit area ulcers [32], and its combination with omega-three has beneficial effects on the inflammatory phase [33]. However, omega-3 supplementation alone has harmful effects on healing [31].
Beyond macronutrients, several micronutrients play a crucial office in the wound healing process, as extensively reviewed [7,8,9,33]. Arginine and glutamine exhibit several metabolic, enzymatic, antioxidant, and anti-inflammatory properties 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, lone or in combination, is still controversial [43,44], probably due to differences in report design, patient characteristics, and blazon of supplementation. Most of the bear witness comes from inquiry on vitamins, with several lines of evidence supporting the benefits of vitamin A [33,47,48], vitamin B [49], vitamin C [8,29,l] and vitamin D [53,54] supplementation. However, to what extent they support wound healing process remains unclear until at present. For case, vitamin C seems to human activity simply in combination with zinc and arginine [51], while vitamin E appears to counteract the benefits of vitamin A [56]. Among minerals, zinc is essential for the inflammatory, proliferative, and remodeling phases past promoting allowed response, collagen product, fibroblast proliferation, and epithelialization [8]. Accordingly, topical zinc administration to surgical wounds significantly facilitates wound healing process [58]. These findings cumulatively advise that nutritional approaches might be useful in the treatment of wounds, particularly of chronic non-healing wounds [10]. Yet, benefits in non-deficient patients are currently nether contend [9], and further research should have into account conditions that touch food metabolism, such as diabetes and potential nutrient–food interactions [58].
three. Conclusions
In conclusion, nosotros support the notion that curcumin could be considered as a wound healing agent, peculiarly if topically administered. However, near of the electric current noesis is derived from in vitro and in vivo investigations, while studies in wound patients remain scarce or controversial. Moreover, since nutrition and nutrients in full general might affect the wound healing process, nutritional assessment of patients at risk of not-healing wounds could be the first footstep towards prevention and handling. All the same, further enquiry is recommended to develop appropriate nutritional approaches for wound direction.
Abbreviations
| AAWC | Advancement of Wound Care |
| GSH | Glutathione |
| HtwoOii | Hydrogen Peroxide |
| IGF-1 | Insulin-Like Growth Factor-1 |
| IL-1 | Interleukin-1 |
| NF-κB | Nuclear Factor κB |
| O2 − | Hydrogen Superoxide |
| PDGF | Platelet-Derived Growth Factor |
| PPAR-γ | Peroxisome Proliferator-Activated Receptor-Gamma |
| ROS | Reactive Oxygen Species |
| TGF | Transforming Growth Factor |
| TLR4-MD2 | Myeloid Differentiation Protein 2-TLR 4 Co-Receptor |
| TNF-α | Tumor Necrosis Factor Alpha |
| VDR | Vitamin D Receptor |
| WHO | Earth Health Organization |
Author Contributions
Conceptualization, A.1000., M.B., A.A. and K.B.; methodology, A.M. and One thousand.B.; writing—original typhoon preparation, A.M., G.F., R.M.Southward.L., M.Eastward., and A.A.; writing—review and editing, all the authors.
Funding
This research was partially funded by the Department of Medical and Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, Catania, Italy.
Conflicts of Interest
The authors declare no conflict of involvement.
References
1. Martin P. Wound healing—Aiming for perfect skin regeneration. Science. 1997;276:75–81. doi: 10.1126/scientific discipline.276.5309.75. [PubMed] [CrossRef] [Google Scholar]
ii. Vocalist A.J., Clark R.A. Cutaneous wound healing. Northward. Engl. J. Med. 1999;341:738–746. doi: 10.1056/NEJM199909023411006. [PubMed] [CrossRef] [Google Scholar]
iii. Harding K.G., Morris H.L., Patel G.K. Science, medicine and the future: Healing chronic wounds. BMJ. 2002;324:160–163. doi: 10.1136/bmj.324.7330.160. [PMC gratuitous article] [PubMed] [CrossRef] [Google Scholar]
iv. Reiber G.Eastward. Diabetic foot care. Financial implications and practice guidelines. Diabetes Care. 1992;fifteen(Suppl. i):29–31. doi: 10.2337/diacare.fifteen.one.S29. [PubMed] [CrossRef] [Google Scholar]
5. Sen C.K., Gordillo One thousand.M., Roy South., Kirsner R., Lambert L., Hunt T.M., Gottrup F., Gurtner One thousand.C., Longaker M.T. Human peel wounds: A major and snowballing threat to public wellness and the economy. Wound Repair Regen. 2009;17:763–771. doi: 10.1111/j.1524-475X.2009.00543.ten. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
half-dozen. Serena T.Eastward. A Global Perspective on Wound Care. Adv. Wound Care (New Rochelle) 2014;3:548–552. doi: 10.1089/wound.2013.0460. [PMC complimentary article] [PubMed] [CrossRef] [Google Scholar]
7. Quain A.Thou., Khardori N.M. Nutrition in Wound Intendance Management: A Comprehensive Overview. Wounds. 2015;27:327–335. [PubMed] [Google Scholar]
viii. Harris C.L., Fraser C. Malnutrition in the institutionalized elderly: The furnishings on wound healing. Ostomy Wound Manag. 2004;50:54–63. [PubMed] [Google Scholar]
9. Thompson C., Fuhrman K.P. Nutrients and wound healing: Still searching for the magic bullet. Nutr. Clin. Pract. 2005;20:331–347. doi: 10.1177/0115426505020003331. [PubMed] [CrossRef] [Google Scholar]
10. Enoch S., Greyness J.E., Harding M.M. ABC of wound healing. Non-surgical and drug treatments. BMJ. 2006;332:900–903. doi: ten.1136/bmj.332.7546.900. [PMC gratis article] [PubMed] [CrossRef] [Google Scholar]
11. Akbik D., Ghadiri Thou., Chrzanowski W., Rohanizadeh R. Curcumin as a wound healing agent. Life Sci. 2014;116:one–7. doi: 10.1016/j.lfs.2014.08.016. [PubMed] [CrossRef] [Google Scholar]
12. Agrawal D.K., Mishra P.K. Curcumin and its analogues: Potential anticancer agents. Med. Res. Rev. 2010;30:818–860. doi: 10.1002/med.20188. [PubMed] [CrossRef] [Google Scholar]
13. Lima C.F., Pereira-Wilson C., Rattan S.I. Curcumin induces heme oxygenase-1 in normal human skin fibroblasts through redox signaling: Relevance for anti-aging intervention. Mol. Nutr. Food Res. 2011;55:430–442. doi: 10.1002/mnfr.201000221. [PubMed] [CrossRef] [Google Scholar]
fourteen. Arablou T., Kolahdouz-Mohammadi R. Curcumin and endometriosis: Review on potential roles and molecular mechanisms. Biomed. Pharmacother. 2018;97:91–97. doi: 10.1016/j.biopha.2017.10.119. [PubMed] [CrossRef] [Google Scholar]
15. Falanga V. Wound healing and its impairment in the diabetic pes. Lancet. 2005;366:1736–1743. doi: 10.1016/S0140-6736(05)67700-8. [PubMed] [CrossRef] [Google Scholar]
sixteen. Velnar T., Bailey T., Smrkolj 5. The wound healing process: An overview of the cellular and molecular mechanisms. J. Int. Med. Res. 2009;37:1528–1542. doi: 10.1177/147323000903700531. [PubMed] [CrossRef] [Google Scholar]
17. Topman G., Lin F.H., Gefen A. The natural medications for wound healing—Curcumin, Aloe-Vera and Ginger—Do non induce a significant outcome on the migration kinematics of cultured fibroblasts. J. Biomech. 2013;46:170–174. doi: 10.1016/j.jbiomech.2012.09.015. [PubMed] [CrossRef] [Google Scholar]
18. Falanga 5. The chronic wound: Impaired healing and solutions in the context of wound bed preparation. Blood Cells Mol. Dis. 2004;32:88–94. doi: 10.1016/j.bcmd.2003.09.020. [PubMed] [CrossRef] [Google Scholar]
19. Santoro M.M., Gaudino G. Cellular and molecular facets of keratinocyte reepithelization during wound healing. Exp. Cell Res. 2005;304:274–286. doi: 10.1016/j.yexcr.2004.10.033. [PubMed] [CrossRef] [Google Scholar]
20. Iyer V., Pumiglia K., DiPersio C.M. Alpha3beta1 integrin regulates MMP-9 mRNA stability in immortalized keratinocytes: A novel machinery of integrin-mediated MMP gene expression. J. Prison cell Sci. 2005;118:1185–1195. doi: 10.1242/jcs.01708. [PubMed] [CrossRef] [Google Scholar]
21. Choma D.P., Pumiglia K., DiPersio C.M. Integrin alpha3beta1 directs the stabilization of a polarized lamellipodium in epithelial cells through activation of Rac1. J. Prison cell Sci. 2004;117:3947–3959. doi: 10.1242/jcs.01251. [PubMed] [CrossRef] [Google Scholar]
22. Nahm Westward.K., Philpot B.D., Adams Yard.One thousand., Badiavas E.Five., Zhou L.H., Butmarc J., Bear M.F., Falanga V. Significance of Northward-methyl-D-aspartate (NMDA) receptor-mediated signaling in human keratinocytes. J. Jail cell. Physiol. 2004;200:309–317. doi: 10.1002/jcp.20010. [PubMed] [CrossRef] [Google Scholar]
24. Katsarou A., Gudbjörnsdottir S., Rawshani A., Dabelea D., Bonifacio E., Anderson B.J., Jacobsen L.M., Schatz D.A., Lernmark Å. Type 1 diabetes mellitus. Nat. Rev. Dis. Primers. 2017;3:17016. doi: x.1038/nrdp.2017.16. [PubMed] [CrossRef] [Google Scholar]
25. Russell L. The importance of patients' nutritional status in wound healing. Br. J. Nurs. 2001;10:S42–S49. doi: 10.12968/bjon.2001.10.Sup1.5336. [PubMed] [CrossRef] [Google Scholar]
26. Breslow R.A., Hallfrisch J., Guy D.M., Crawley B., Goldberg A.P. The importance of dietary protein in healing pressure ulcers. J. Am. Geriatr. Soc. 1993;41:357–362. doi: 10.1111/j.1532-5415.1993.tb06940.ten. [PubMed] [CrossRef] [Google Scholar]
27. Chen C.C., Schilling Fifty.Southward., Lyder C.H. A concept analysis of malnutrition in the elderly. J. Adv. Nurs. 2001;36:131–142. doi: 10.1046/j.1365-2648.2001.01950.x. [PubMed] [CrossRef] [Google Scholar]
28. Evans C. Malnutrition in the elderly: A multifactorial failure to thrive. Perm. J. 2005;nine:38–41. doi: 10.7812/TPP/05-056. [PMC free commodity] [PubMed] [CrossRef] [Google Scholar]
29. Casey Thou. Nutritional support in wound healing. Nurs. Stand. 2003;17:55–58. doi: 10.7748/ns.17.23.55.s57. [PubMed] [CrossRef] [Google Scholar]
thirty. Todorovic V. Food and wounds: Nutritional factors in wound formation and healing. Br. J. Community Nurs. 2002;7:43–54. doi: 10.12968/bjcn.2002.7.Sup2.12981. [PubMed] [CrossRef] [Google Scholar]
31. Albina J.E., Gladden P., Walsh W.R. Detrimental effects of an omega-3 fatty acid-enriched nutrition on wound healing. JPEN J. Parenter. Enter. Nutr. 1993;17:519–521. doi: ten.1177/0148607193017006519. [PubMed] [CrossRef] [Google Scholar]
32. Theilla M., Schwartz B., Cohen J., Shapiro H., Anbar R., Singer P. Impact of a nutritional formula enriched in fish oil and micronutrients on pressure level ulcers in disquisitional care patients. Am. J. Crit. Care. 2012;21:e102–e109. doi: 10.4037/ajcc2012187. [PubMed] [CrossRef] [Google Scholar]
33. Molnar J.A., Underdown M.J., Clark Westward.A. Nutrition and Chronic Wounds. Adv. Wound Care (New Rochelle) 2014;3:663–681. doi: 10.1089/wound.2014.0530. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
34. Debats I.B., Wolfs T.Chiliad., Gotoh T., Cleutjens J.P., Peutz-Kootstra C.J., van der Hulst R.R. Role of arginine in superficial wound healing in man. Nitric Oxide. 2009;21:175–183. doi: 10.1016/j.niox.2009.07.006. [PubMed] [CrossRef] [Google Scholar]
35. Schäffer Thousand.R., Tantry U., Thornton F.J., Barbul A. Inhibition of nitric oxide synthesis in wounds: Pharmacology and upshot on accumulation of collagen in wounds in mice. Eur. J. Surg. 1999;165:262–267. doi: 10.1080/110241599750007153. [PubMed] [CrossRef] [Google Scholar]
36. Kirk Due south.J., Hurson M., Regan M.C., Holt D.R., Wasserkrug H.L., Barbul A. Arginine stimulates wound healing and allowed function in elderly human beings. Surgery. 1993;114:155–159; discussion 160. [PubMed] [Google Scholar]
37. Wu G., Bazer F.W., Davis T.A., Kim South.W., Li P., Marc Rhoads J., Carey Satterfield K., Smith Southward.B., Spencer T.E., Yin Y. Arginine metabolism and nutrition in growth, health and illness. Amino Acids. 2009;37:153–168. doi: 10.1007/s00726-008-0210-y. [PMC gratis article] [PubMed] [CrossRef] [Google Scholar]
38. Barbul A. Proline precursors to sustain Mammalian collagen synthesis. J. Nutr. 2008;138:2021S–2024S. doi: 10.1093/jn/138.10.2021S. [PubMed] [CrossRef] [Google Scholar]
39. Leigh B., Desneves K., Rafferty J., Pearce L., Male monarch Due south., Woodward 1000.C., Brown D., Martin R., Crowe T.C. The effect of different doses of an arginine-containing supplement on the healing of pressure ulcers. J. Wound Care. 2012;21:150–156. doi: ten.12968/jowc.2012.21.three.150. [PubMed] [CrossRef] [Google Scholar]
forty. Wischmeyer P.E. Glutamine and heat shock protein expression. Nutrition. 2002;eighteen:225–228. doi: ten.1016/S0899-9007(01)00796-1. [PubMed] [CrossRef] [Google Scholar]
41. Newsholme P. Why is 50-glutamine metabolism important to cells of the immune system in health, postinjury, surgery or infection? J. Nutr. 2001;131:2515S–2522S; discussion 2523S–2514S. doi: 10.1093/jn/131.9.2515S. [PubMed] [CrossRef] [Google Scholar]
42. Ardawi M.S. Glutamine and glucose metabolism in man peripheral lymphocytes. Metabolism. 1988;37:99–103. doi: 10.1016/0026-0495(88)90036-4. [PubMed] [CrossRef] [Google Scholar]
43. Peng X., Yan H., Y'all Z., Wang P., Wang S. Clinical and poly peptide metabolic efficacy of glutamine granules-supplemented enteral diet in severely burned patients. Burns. 2005;31:342–346. doi: 10.1016/j.burns.2004.10.027. [PubMed] [CrossRef] [Google Scholar]
44. Blass S.C., Goost H., Tolba R.H., Stoffel-Wagner B., Kabir K., Burger C., Stehle P., Ellinger S. Fourth dimension to wound closure in trauma patients with disorders in wound healing is shortened by supplements containing antioxidant micronutrients and glutamine: A PRCT. Clin. Nutr. 2012;31:469–475. doi: 10.1016/j.clnu.2012.01.002. [PubMed] [CrossRef] [Google Scholar]
45. Stadelmann W.K., Digenis A.G., Tobin 1000.R. Impediments to wound healing. Am. J. Surg. 1998;176:39S–47S. doi: x.1016/S0002-9610(98)00184-6. [PubMed] [CrossRef] [Google Scholar]
46. Reichrath J., Lehmann B., Carlberg C., Varani J., Zouboulis C.C. Vitamins as hormones. Horm. Metab. Res. 2007;39:71–84. doi: x.1055/southward-2007-958715. [PubMed] [CrossRef] [Google Scholar]
47. Chase T.1000., Ehrlich H.P., Garcia J.A., Dunphy J.E. Effect of vitamin A on reversing the inhibitory effect of cortisone on healing of open up wounds in animals and human being. Ann. Surg. 1969;170:633–641. doi: 10.1097/00000658-196910000-00014. [PMC gratis article] [PubMed] [CrossRef] [Google Scholar]
48. Wicke C., Halliday B., Allen D., Roche N.Due south., Scheuenstuhl H., Spencer M.K., Roberts A.B., Hunt T.K. Effects of steroids and retinoids on wound healing. Arch. Surg. 2000;135:1265–1270. doi: 10.1001/archsurg.135.11.1265. [PubMed] [CrossRef] [Google Scholar]
49. Williams J.Z., Barbul A. Nutrition and wound healing. Crit. Care Nurs. Clin. N. Am. 2012;24:179–200. doi: x.1016/j.ccell.2012.03.001. [PubMed] [CrossRef] [Google Scholar]
50. Shepherd A.A. Nutrition for optimum wound healing. Nurs. Stand up. 2003;18:55–58. [PubMed] [Google Scholar]
51. Ellinger S., Stehle P. Efficacy of vitamin supplementation in situations with wound healing disorders: Results from clinical intervention studies. Curr. Opin. Clin. Nutr. Metab. Care. 2009;12:588–595. doi: ten.1097/MCO.0b013e328331a5b5. [PubMed] [CrossRef] [Google Scholar]
52. Zhang Y.G., Wu S., Sun J. Vitamin D, Vitamin D Receptor, and Tissue Barriers. Tissue Barriers. 2013;1:e23118. doi: ten.4161/tisb.23118. [PMC costless article] [PubMed] [CrossRef] [Google Scholar]
53. Burkievcz C.J., Skare T.L., Malafaia O., Nassif P.A., Ribas C.South., Santos L.R. Vitamin D deficiency in patients with chronic venous ulcers. Rev. Col. Bras. Cir. 2012;39:lx–63. doi: 10.1590/S0100-69912012000100012. [PubMed] [CrossRef] [Google Scholar]
54. Kalava U.R., Cha Southward.S., Takahashi P.Y. Association between vitamin D and pressure level ulcers in older convalescent adults: Results of a matched case-control study. Clin. Interv. Crumbling. 2011;half dozen:213–219. doi: 10.2147/CIA.S23109. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
55. Mazzotta M.Y. Nutrition and wound healing. J. Am. Podiatr. Med. Assoc. 1994;84:456–462. doi: 10.7547/87507315-84-9-456. [PubMed] [CrossRef] [Google Scholar]
56. Trujillo East.B. Effects of nutritional condition on wound healing. J. Vasc. Nurs. 1993;11:12–18. [PubMed] [Google Scholar]
57. Fosmire Grand.J. Zinc toxicity. Am. J. Clin. Nutr. 1990;51:225–227. doi: 10.1093/ajcn/51.2.225. [PubMed] [CrossRef] [Google Scholar]
58. Lansdown A.B., Mirastschijski U., Stubbs Northward., Scanlon E., Agren M.S. Zinc in wound healing: Theoretical, experimental, and clinical aspects. Wound Repair Regen. 2007;15:2–16. doi: 10.1111/j.1524-475X.2006.00179.x. [PubMed] [CrossRef] [Google Scholar]
59. Milobedzka J., Kostanecki Southward., Lampe V. Zur Kenntnis des Curcumins. Ber. Dtsch. Chem. Ges. 1910;43:2163–2170. doi: 10.1002/cber.191004302168. [CrossRef] [Google Scholar]
lx. Bielefeld Yard.A., Amini-Nik Southward., Alman B.A. Cutaneous wound healing: recruiting developmental pathways for regeneration. Prison cell. Mol. Life Sci. 2013;70:2059–2081. doi: x.1007/s00018-012-1152-9. [PMC costless article] [PubMed] [CrossRef] [Google Scholar]
61. Wu North.C., Wang J.J. Curcumin attenuates liver warm ischemia and reperfusion-induced combined restrictive and obstructive lung affliction past reducing matrix metalloprotease 9 activity. Transplant. Proc. 2014;46:1135–1138. doi: 10.1016/j.transproceed.2013.12.020. [PubMed] [CrossRef] [Google Scholar]
62. Song Z., Revelo X., Shao West., Tian Fifty., Zeng K., Lei H., Dominicus H.Southward., Woo M., Winer D., Jin T. Dietary Curcumin Intervention Targets Mouse White Adipose Tissue Inflammation and Brown Adipose Tissue UCP1 Expression. Obesity (Silver Spring) 2018;26:547–558. doi: 10.1002/oby.22110. [PubMed] [CrossRef] [Google Scholar]
63. Hunter C.J., De Plaen I.G. Inflammatory signaling in NEC: Role of NF-κB, cytokines and other inflammatory mediators. Pathophysiology. 2014;21:55–65. doi: 10.1016/j.pathophys.2013.11.010. [PMC complimentary article] [PubMed] [CrossRef] [Google Scholar]
64. Merrell J.G., McLaughlin S.W., Tie L., Laurencin C.T., Chen A.F., Nair 50.South. Curcumin-loaded poly(epsilon-caprolactone) nanofibres: Diabetic wound dressing with anti-oxidant and anti-inflammatory backdrop. Clin. Exp. Pharmacol. Physiol. 2009;36:1149–1156. doi: 10.1111/j.1440-1681.2009.05216.x. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
65. Wang J., Wang H., Zhu R., Liu Q., Fei J., Wang S. Anti-inflammatory activity of curcumin-loaded solid lipid nanoparticles in IL-1β transgenic mice subjected to the lipopolysaccharide-induced sepsis. Biomaterials. 2015;53:475–483. doi: ten.1016/j.biomaterials.2015.02.116. [PubMed] [CrossRef] [Google Scholar]
66. Antoine F., Girard D. Curcumin increases gelatinase activity in human neutrophils by a p38 mitogen-activated protein kinase (MAPK)-independent mechanism. J. Immunotoxicol. 2015;12:188–193. doi: x.3109/1547691X.2014.917749. [PubMed] [CrossRef] [Google Scholar]
67. Li H.Y., Yang M., Li Z., Meng Z. Curcumin inhibits angiotensin Two-induced inflammation and proliferation of rat vascular polish musculus cells by elevating PPAR-γ activity and reducing oxidative stress. Int. J. Mol. Med. 2017;39:1307–1316. doi: 10.3892/ijmm.2017.2924. [PubMed] [CrossRef] [Google Scholar]
68. Zhang Y., Liu Z., Wu J., Bai B., Chen H., Xiao Z., Chen Fifty., Zhao Y., Lum H., Wang Y., et al. New MD2 inhibitors derived from curcumin with improved anti-inflammatory activity. Eur. J. Med. Chem. 2018;148:291–305. doi: 10.1016/j.ejmech.2018.02.008. [PubMed] [CrossRef] [Google Scholar]
69. Frey R.Southward., Malik A.B. Oxidant signaling in lung cells. Am. J. Physiol. Lung Jail cell. Mol. Physiol. 2004;286:L1–L3. doi: 10.1152/ajplung.00337.2003. [PubMed] [CrossRef] [Google Scholar]
lxx. Panchatcharam G., Miriyala S., Gayathri V.S., Suguna 50. Curcumin improves wound healing by modulating collagen and decreasing reactive oxygen species. Mol. Cell. Biochem. 2006;290:87–96. doi: 10.1007/s11010-006-9170-2. [PubMed] [CrossRef] [Google Scholar]
71. Roy Due south., Khanna South., Nallu Chiliad., Hunt T.K., Sen C.Chiliad. Dermal wound healing is subject to redox control. Mol. Ther. 2006;13:211–220. doi: ten.1016/j.ymthe.2005.07.684. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
72. Imlay J.A. Pathways of oxidative damage. Annu. Rev. Microbiol. 2003;57:395–418. doi: 10.1146/annurev.micro.57.030502.090938. [PubMed] [CrossRef] [Google Scholar]
73. Matés J.1000., Segura J.A., Alonso F.J., Márquez J. Roles of dioxins and heavy metals in cancer and neurological diseases using ROS-mediated mechanisms. Free Radic. Biol. Med. 2010;49:1328–1341. doi: 10.1016/j.freeradbiomed.2010.07.028. [PubMed] [CrossRef] [Google Scholar]
74. Gopinath D., Ahmed Chiliad.R., Gomathi K., Chitra Thousand., Sehgal P.K., Jayakumar R. Dermal wound healing processes with curcumin incorporated collagen films. Biomaterials. 2004;25:1911–1917. doi: 10.1016/S0142-9612(03)00625-2. [PubMed] [CrossRef] [Google Scholar]
75. Tapia E., Sánchez-Lozada L.Grand., García-Niño West.R., García E., Cerecedo A., García-Approach F.E., Osorio H., Arellano A., Cristóbal-García Chiliad., Loredo M.L., et al. Curcumin prevents maleate-induced nephrotoxicity: Relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and action of respiratory complex I. Free Radic. Res. 2014;48:1342–1354. doi: ten.3109/10715762.2014.954109. [PubMed] [CrossRef] [Google Scholar]
76. Zheng Q.T., Yang Z.H., Yu L.Y., Ren Y.Y., Huang Q.10., Liu Q., Ma Ten.Y., Chen Z.K., Wang Z.B., Zheng Ten. Synthesis and antioxidant activity of curcumin analogs. J. Asian Nat. Prod. Res. 2017;19:489–503. doi: 10.1080/10286020.2016.1235562. [PubMed] [CrossRef] [Google Scholar]
77. Reddy A.C., Lokesh B.R. Effect of dietary turmeric (Curcuma longa) on iron-induced lipid peroxidation in the rat liver. Nutrient Chem. Toxicol. 1994;32:279–283. doi: 10.1016/0278-6915(94)90201-one. [PubMed] [CrossRef] [Google Scholar]
78. Subudhi U., Chainy G.B. Expression of hepatic antioxidant genes in l-thyroxine-induced hyperthyroid rats: Regulation by vitamin E and curcumin. Chem. Biol. Interact. 2010;183:304–316. doi: 10.1016/j.cbi.2009.11.004. [PubMed] [CrossRef] [Google Scholar]
79. Dai C., Tang Due south., Li D., Zhao K., Xiao X. Curcumin attenuates quinocetone-induced oxidative stress and genotoxicity in human hepatocyte L02 cells. Toxicol. Mech. Methods. 2015;25:340–346. doi: 10.3109/15376516.2015.1045659. [PubMed] [CrossRef] [Google Scholar]
80. Phan T.T., See P., Lee S.T., Chan South.Y. Protective effects of curcumin against oxidative damage on skin cells in vitro: Its implication for wound healing. J. Trauma. 2001;51:927–931. doi: 10.1097/00005373-200111000-00017. [PubMed] [CrossRef] [Google Scholar]
81. Zhang Y., Cao H., Yu Z., Peng H.Y., Zhang C.J. Curcumin inhibits endometriosis endometrial cells by reducing estradiol production. Iran. J. Reprod. Med. 2013;xi:415–422. [PMC free article] [PubMed] [Google Scholar]
82. Petroll Due west.1000., Cavanagh H.D., Barry P., Andrews P., Jester J.V. Quantitative assay of stress fiber orientation during corneal wound contraction. Pt 2 J. Prison cell Sci. 1993;104:353–363. [PubMed] [Google Scholar]
83. Durgaprasad South., Reetesh R., Hareesh Chiliad., Rajput R. Effect of topical curcumin preparation (BIOCURCUMAX) on burn wound healing in rats. J. Pharm. Biomed. Sci. (JPBMS) 2011;viii:1–3. [Google Scholar]
84. Dai M., Zheng X., Xu 10., Kong X., Li X., Guo G., Luo F., Zhao Ten., Wei Y.Q., Qian Z. Chitosan-alginate sponge: Training and application in curcumin delivery for dermal wound healing in rat. J. Biomed. Biotechnol. 2009;2009:595126. doi: 10.1155/2009/595126. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
85. Mohanty C., Das One thousand., Sahoo S.K. Sustained wound healing activity of curcumin loaded oleic acid based polymeric bandage in a rat model. Mol. Pharm. 2012;9:2801–2811. doi: x.1021/mp300075u. [PubMed] [CrossRef] [Google Scholar]
86. Jagetia G.C., Rajanikant K.G. Acceleration of wound repair past curcumin in the excision wound of mice exposed to different doses of fractionated γ radiations. Int. Wound J. 2012;9:76–92. doi: 10.1111/j.1742-481X.2011.00848.ten. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
87. Welch K.P., Odland G.F., Clark R.A. Temporal relationships of F-actin parcel formation, collagen and fibronectin matrix assembly, and fibronectin receptor expression to wound contraction. J. Cell Biol. 1990;110:133–145. doi: 10.1083/jcb.110.1.133. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
88. Sidhu Chiliad.S., Singh A.Thousand., Thaloor D., Banaudha K.M., Patnaik G.K., Srimal R.C., Maheshwari R.K. Enhancement of wound healing by curcumin in animals. Wound Repair Regen. 1998;six:167–177. doi: 10.1046/j.1524-475X.1998.60211.10. [PubMed] [CrossRef] [Google Scholar]
89. Sidhu G.S., Mani H., Gaddipati J.P., Singh A.K., Seth P., Banaudha K.K., Patnaik G.1000., Maheshwari R.Yard. Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice. Wound Repair Regen. 1999;7:362–374. doi: 10.1046/j.1524-475X.1999.00362.x. [PubMed] [CrossRef] [Google Scholar]
ninety. Brown D.50., Kao Due west.W., Greenhalgh D.G. Apoptosis down-regulates inflammation under the advancing epithelial wound border: Delayed patterns in diabetes and comeback with topical growth factors. Surgery. 1997;121:372–380. doi: x.1016/S0039-6060(97)90306-8. [PubMed] [CrossRef] [Google Scholar]
91. Kant V., Gopal A., Kumar D., Pathak N.N., Ram K., Jangir B.50., Tandan Due south.M. Curcumin-induced angiogenesis hastens wound healing in diabetic rats. J. Surg. Res. 2015;193:978–988. doi: ten.1016/j.jss.2014.10.019. [PubMed] [CrossRef] [Google Scholar]
92. Abe Y., Hashimoto S., Horie T. Curcumin inhibition of inflammatory cytokine production by man peripheral blood monocytes and alveolar macrophages. Pharmacol. Res. 1999;39:41–47. doi: 10.1006/phrs.1998.0404. [PubMed] [CrossRef] [Google Scholar]
93. Balogun E., Hoque Thousand., Gong P., Killeen E., Light-green C.J., Foresti R., Alam J., Motterlini R. Curcumin activates the haem oxygenase-1 cistron via regulation of Nrf2 and the antioxidant-responsive chemical element. Biochem. J. 2003;371:887–895. doi: ten.1042/bj20021619. [PMC free commodity] [PubMed] [CrossRef] [Google Scholar]
94. Huang 1000.T., Lysz T., Ferraro T., Abidi T.F., Laskin J.D., Conney A.H. Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Res. 1991;51:813–819. [PubMed] [Google Scholar]
95. Woo J.H., Kim Y.H., Choi Y.J., Kim D.Grand., Lee K.S., Bae J.H., Min D.S., Chang J.S., Jeong Y.J., Lee Y.H., et al. Molecular mechanisms of curcumin-induced cytotoxicity: Induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-40 and IAP, the release of cytochrome c and inhibition of Akt. Carcinogenesis. 2003;24:1199–1208. doi: ten.1093/carcin/bgg082. [PubMed] [CrossRef] [Google Scholar]
96. Maugeri A., Mazzone M.Thou., Giuliano F., Vinciguerra Grand., Basile Grand., Barchitta M., Agodi A. Curcumin Modulates Dna Methyltransferase Functions in a Cellular Model of Diabetic Retinopathy. Oxid. Med. Cell. Longev. 2018;2018:5407482. doi: 10.1155/2018/5407482. [PMC complimentary article] [PubMed] [CrossRef] [Google Scholar]
97. Lewis C.J., Mardaryev A.N., Sharov A.A., Fessing Thousand.Y., Botchkarev V.A. The Epigenetic Regulation of Wound Healing. Adv. Wound Care (New Rochelle) 2014;3:468–475. doi: 10.1089/wound.2014.0522. [PMC free commodity] [PubMed] [CrossRef] [Google Scholar]
98. Maugeri A., Barchitta M., Mazzone Thousand.One thousand., Giuliano F., Basile Grand., Agodi A. Resveratrol modulates SIRT1 and DNMT functions and restores LINE-one methylation levels in ARPE-19 cells under oxidative stress and inflammation. Int. J. Mol. Sci. 2018;19:2118. doi: 10.3390/ijms19072118. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
99. Ravindranath 5., Chandrasekhara N. Absorption and tissue distribution of curcumin in rats. Toxicology. 1980;16:259–265. doi: 10.1016/0300-483X(lxxx)90122-5. [PubMed] [CrossRef] [Google Scholar]
100. Asai A., Miyazawa T. Occurrence of orally administered curcuminoid equally glucuronide and glucuronide/sulfate conjugates in rat plasma. Life Sci. 2000;67:2785–2793. doi: 10.1016/S0024-3205(00)00868-seven. [PubMed] [CrossRef] [Google Scholar]
101. Hegge A.B., Andersen T., Melvik J.E., Bruzell Due east., Kristensen Southward., Tønnesen H.H. Conception and bacterial phototoxicity of curcumin loaded alginate foams for wound handling applications: Studies on curcumin and curcuminoides XLII. J. Pharm. Sci. 2011;100:174–185. doi: 10.1002/jps.22263. [PubMed] [CrossRef] [Google Scholar]
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