Healing mechanisms in burn wounds of herbal therapies.
Burn wound healing is a complex process including inflammation, epithelialization, granulation, neovascularization, and wound contraction. Modern therapies present a large number of options, while traditional therapies are promising effective choices. Plant-based products have been used in the treatment of wounds for centuries worldwide. Recently, the mechanisms behind many of these traditional therapies could be explained in detail. The most commonly found mechanisms behind the herbal source products supporting wound healing are mostly their antioxidant, anti-inflammatory, antimicrobial, cell proliferative, and angiogenic effects. However there is not much more studies demonstrated in patients except Aloe vera and Avena sp., herbal treatment still show a lot of promise in the future. It is important not to ignore possible toxic and allergic effects of plants and phytochemical agents, but the studies mostly resulted with antitoxic effects. Several herbs show efficient results with therapies of wounds also in burn wounds, which may be considered as an option for treatment. On the other hand, herbal treatment in burn wounds still needs to have more clinical and pharmaceutical studies to place in modern therapies safely.
- burn wound
- herbal therapy
- wound healing
Skin is the largest organ of the human body that protects the internal organs from the external environment and prevents body dehydration. It can be traumatized by burn injuries, chronic wounds, excision, tumors, and other dermatological conditions . Burns are one of the most commonly seen trauma incidents and burn wounds need a meticulous care for progress, which causes major medical and economic costs . Burns have extensive categories that may result from heat, cold, chemical, or radiation exposure causing acute cutaneous wounds . Burn wounds are classified into three subgroups according to the depth as first degree (superficial), second degree (partial thickness), and third degree (full thickness) . Process of the wound healing has complicated pathways that do not occur in a linear way and can progress forward or backward during the phases depending on various intrinsic and extrinsic factors . After the cutaneous injury, hemostasis is achieved with the activation of platelets resulting in clot formation, which essentially acts as a temporary wound closure mechanism . Burn wound healing is a complex process including inflammation due to the disruption of blood vessels and extravasation of blood constituents, reepithelialization, formation of granulation tissue handled by macrophages and fibroblasts that are responsible for the recovery of the extracellular matrix (ECM), neovascularization as well as migration and mitogenic stimulation of endothelial cells and wound contraction as a result of the interaction between cells, ECM, and cytokines . Neutrophils begin placing to the injury area within hours of the injury, by the effects of platelet-derived growth factors (PDGF), transforming growth factor-beta (TGF-B), and fibroblast growth factor (FGF), that are potent chemotactic agents for neutrophils .
Several biochemicals are involved in burn healing process including matrix metalloproteinases, superoxide dismutase, catalase, reduced glutathione, malondialdehyde, myeloperoxidase, vascular endothelial growth factor, hydroxyproline, hexosamine, ascorbic acid (vitamin C) and protein content in damaged and surrounding tissue, serum levels of aspartate transaminase, alanine transaminase, lactate dehydrogenase, blood urea nitrogen, creatinine as indicators of liver and kidney damage, and tumor necrosis factor (TNF) for the evaluation of generalized tissue damage . Moreover, wound repair process has also a chronic progression because of oxygen free radicals. Oxidative stress causes delay in healing and concludes with secondary tissue damage. It is assumed that antioxidant therapy may have a defense effect by decreasing free oxygen radicals and strengthening cellular antioxidant mechanisms, which supports the healing process of the wound . Consequently, compounds playing roles as free-radical neutralizers that include antimicrobial properties may have an important effect in enhancing wound healing. Several traditional herbal-based therapies have been shown to possess antioxidant activity and also enhance wound healing in in vitro studies .
Excessive tissue growing may result with aberrant patterns of wounds. Hypertrophic scars and keloids are deviant form results of wound healing that are also seen after burn wounds. Aberrant function of fibroblasts and exaggerate accumulation of ECM during wound healing with a dysregulated response to cutaneous injuries, result in an excessive deposition of collagen. Hypertrophic scars have a raised and firm surface with red or pink in color and usually limited to wound area, while keloids have raised firm and irregular surface usually dark red and pigmented in color that extends into the neighboring skin. Keloids are tougher lesions to treat because of not regressing, also difficult to manage surgically, that do not provoke scar contractures with time, contrary to hypertrophic scars [11, 12]. There are plant-based agents that may inhibit nuclear factor κB (NF-κB) and TGF-β1 signaling in keloid fibroblasts and also decrease ECM production .
Various wound care products are used for the management of scars, like autografts and allografts, creams and solutions, wound dressings and alternative tissue-engineered skin substitutes . In recent years, a variety of commercially available wound dressings were launched. However, they possess certain critical limitations such as addition of antimicrobial agents, which might include cytotoxic effects, especially on prolonged treatment period, causing to delay wound healing. Some of the marketed dressings lose their moisturizing effect, which makes them adhere to the surface of the wound and damage the newly formed epithelium . After burn damage, the treatment of skin needs the use of several drugs administered separately or combined, and it is a complex and painful process .
In traditional medicine, there are various phytochemicals that are used for wound healing supplying enhanced healing process via anti-inflammatory or antioxidant activity . However, several herbal-sourced phytochemicals have shown some efficacy in animal models on the treatment of burn wounds; only a few herb-derived phytochemicals have been studied in human trials such as
2. Herbal therapies
Extensive study results showed that herbs especially
Curcumin is a polyphenol compound, diferuloylmethane, responsible for the yellow pigmentation. Curcumin is a chemical compound present in the Asian spice named turmeric or
In hypertrophic scarring and keloids, there is an abundance of TGF-B1 expression, fibroblast proliferation, and excess collagen and ECM synthesis . In scleroderma, which is another fibrotic skin disease, curcumin has also been shown to inhibit TGF-B1 signaling . Curcumin is a potent inhibitor of NF-κB, inhibits TGF-B1 signaling in keloid fibroblasts, and also decreases ECM production . In vitro, it is showed that curcumin also suppresses the proliferation cascades of keloids and hypertrophic scar-acquired fibroblasts .
Honey is a nutritious thick carbohydrate-rich syrup, which was effectively known and used since ancient times in traditional medicine. Today, honey has a broad area being used due to its evidenced therapeutic effects. It is a well-known antibacterial, antiparasitic, pain reliever, and it has proven efficient against respiratory tract infections . Honey has been used as a topical treatment for chronic wounds and burns in traditional medicine by diverse parts around the globe . It has been used for burns in various ancient societies such as Greek and Roman physicians, and also for the treatment of burn wounds . It was shown in a study that Leptospermum honey was potently active against antibiotic-resistant clinical pathogens . Antibacterial features of honey are about its high osmolarity, low pH, and hydrogen peroxide production that accelerate the wound healing process . Since chronic wounds and burns are particularly vulnerable to infections, honey’s antibacterial effect attracts to be a therapy method . The phytochemical components, such as flavonoids and phenolic acids, act as antioxidants due to their free radical removing activities, which save cells from the damage due to free oxygen radicals and decrease the inflammatory response . Its immunomodulatory effects are useful for the management of chronic wounds. Honey is also shown to promote angiogenesis and fibroblast proliferation in human clinical trials . It is shown in rat models of partial-thickness burn injuries, honey usage shortened the period of epithelialization and increased wound contraction compared to vehicle controls . Honey carries protease enzymes that help debridement cleaning out of the wounds . Honey overcomes the hyperinflammatory microenvironment on chronic wounds via its anti-inflammatory effects by the inhibition of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), TNF-a, and IL-6 expression . Also honey contains various compounds including flavonoids, phenolic acids, catalase, peroxidase, carotenoids, and ascorbic acid, which possess antioxidant properties that can neutralize the abundance of free radicals found in chronic wounds [35, 36].
Using honey over burned area supplies an advantage of wetter environment. It saves the burned surface entirety; also, it is nonadherent and provides a bacterial barrier that prevents cross infection and prevents infecting bacteria . In a systematic review of randomized controlled trials of eight studies in humans comparing the efficacy of honey to silver sulfadiazine-impregnated gauze demonstrated that honey had a superior healing effect, yet burn characteristics were limited to superficial and partial thickness only . Honey debrides the wound, inhibits scar formation, and induces wound healing by stimulating tissue regeneration process so that it reduces the need for skin grafting. There are no adverse effects reported from using honey in burn healing . Honey also has been shown to be protective against hypertrophic scarring as a result of burn wounds. In a randomized controlled trial, the effects of honey were compared to silver sulfadiazine in 104 patients with superficial burns. Hypertrophic scarring and postburn contracture in the honey-treated group have significantly lower incidence in comparison to the silver sulfadiazine-treated group .
Oral and topical administration of
|Herbal therapies||Healing mechanisms in burn wounds|
|Anti-inflammatory [1, 15]|
Antikeloidal effect 
|Antiproliferative, antiangiogenic |
Antikeloidal effect 
|Honey||Antibacterial, antiparasitic, analgesic, antioxidant |
Immunomodulatory effect  Antikeloidal effect 
|Antioxidant [42, 43]|
|Antibacterial, antikeloidal effect |
|Antioxidant, anti-inflammatory [44, 45]|
|Antioxidant [3, 46]|
Anti-inflammatory, antibacterial [39, 46]
|Increasing reepithelialization and keratinization |