**3. Wound healing management**

mechanisms are regulation and sensation. All mentioned provide a crucial set of functions such as enable protection from mechanical impacts and pressure, restrict the influence of temperature changes, lower the potential impact of microorganisms, limit radiation effects and diminish the entrance of different chemicals. Other important skin functions include the regulation of body temperature (e.g. through sweat glands and hair), control over the peripheral circulation and fluid balance, and in the synthesis of vitamin D. Through its extensive nerve cell network, it enables detection and relaying of changes in the environment (e.g. heat/cold, touch and pain). Damage to these networks is called a neuropathy and impairs the sensation of the mentioned functions in the affected areas. The preservation of skin integrity is due to

A wound is trauma-induced defect of the human skin, involving a multitude of endogenous biochemical events and cellular reactions of the immune system [3]. Wounds can compromise patient's well-being, self-image, working capacity and independence. Effective wound management is therefore necessary not only for the individual patient, but has an important

Wound healing is an extremely complex and dynamic process, which includes replacing of devitalized and missing cellular structures and tissue layers. It reflects in a set of biochemical events that integrate into an organized cascade of processes to repair the damaged tissue [5]. Immediately after injury, damaged vessels leak fluid, to which the body responds with haemostasis. Platelets start to aggregate in the wound bed and secrete multiple growth factors that contribute to an effective clot formation to hinder further loss of fluids from the defected area [6]. Simultaneously with the launch of haemostatic mechanisms, the inflammatory phase is induced as well [7]. It is characterized by local vasodilatation, platelet aggregation and phagocytosis, which together with the release of several cytokines, contribute to local inflammation of the wound site. Multiple chemokines, released by platelets, stimulate the immune and other cells (e.g. keratinocytes) to release growth factors and cytokines to regulate various signalling cascades that govern the inflammation and healing in general [8]. Macrophages and other immune cells are stimulated and they migrate towards the wound to dispose cell debris and fight invading bacteria during the wound healing. Angiogenesis occurs at this phase and new blood vessels transport essential nutrients to the wound bed [6]. The next phase in wound healing is the proliferative phase, which is characterized by granulation, wound contraction and epithelialisation. During granulation, fibroblasts form a bed of collagen, followed by the production of new capillaries [7]. During wound contraction, myofibroblasts decrease the size of the wound by gripping the wound edges and pulling them into the wound interior mechanisms that resemble that of smooth muscle cells. After completion of respective processes, unneeded cells undergo apoptosis (controlled cell death) [9]. Epithelialisation is initiated by keratinocytes proliferating and migrating across the wound site [8]. Fibroblasts are activated and differentiated into myofibroblasts that (either indirectly by production of cytokines or directly) regulate other cells to grow and form new epithelial tissue over the wound site. The final wound healing phase is the remodelling

all mentioned functions crucial for maintaining a healthy body [2].

impact also on the community [4].

122 Herbal Medicine

**2. Mechanism of wound healing**

The complex course of the wound healing with the various physiological events that occur simultaneously, as well as consecutively, is vulnerable to possible external interferences (e.g. infections) on one side, as well enables modulation, and hence improvement of the healing performance, through active treatment solutions (e.g. multifunctional wound dressings) [12, 13]. Among the most desired activities are the ones providing anti-inflammatory, antimicrobial, analgesic and antioxidant activities, regardless of the exact underlying mechanism of action [14].

Shortly after the injury, it is during the acute inflammatory response that different cytokines are formed. These are crucial for orchestration of the specific tissue growth, its repair, and hence regeneration [15]. Nevertheless, if this inflammation step persists, it can negatively affect the wound process, namely it leads to vicious cycle of ongoing inflammation, preventing the wound to reach the remodelling phase. If this happens, delays in wound closure occur, which are often accompanied with the increased sensation of pain in the wounded area and its surroundings that can additionally hinder the healing process [16]. Based on these findings about the wound healing physiology, a lot of research has focused on the development of therapeutic approaches that would provide an anti-inflammatory and pain relieving activity to wound dressings [17].

Part of the inflammation phase of wound healing causes also a coordinated influx of neutrophils to the wound site. One of the actions of neutrophils is also the activation of the so-called 'respiratory burst', which leads to productions of free radicals [25]. These produce oxidative stress that results in lipid peroxidation, DNA damage, and enzyme inactivation (e.g. free-radical scavenger enzymes and others), even those whose main activity is to limit the effects of reactive oxygen species (ROS). Considering the above mentioned, it is clear that antioxidants may be of therapeutic use in several diseases that are connected with potential

Plant-Derived Medicines with Potential Use in Wound Treatment

http://dx.doi.org/10.5772/intechopen.72813

125

Apart from the above-mentioned wound healing aiding activities, others are also reported in literature, e.g. the astringent activity, stimulated epithelisation and effective hydration of the wound site [27]. The most important properties of plant-derived medicines that are beneficial for the wound healing process are depicted in **Figure 2** together with some examples of plants

For thousands of years, we looked to nature for various types of medicinal treatments and plant-based systems continue to play an essential role in the primary health care of many less-developed, as well as developing countries [46]. Many plants and various preparations thereof have been used traditionally in relation to wound treatment, especially due to their immense potential to affect the wound healing process [65]. Plant-derived extracts and/or isolates induce healing and tissue regeneration through multiple connected mechanisms, which often have a synergistic effect on the overall healing efficiency [47]. Many plant-derived medicines (commonly called as phytomedicines) are affordable and cause minimal unwanted side effects [48]. Nevertheless, increasing awareness of their potential activities, especially considering the possible combinations of various plant-derived molecules, which could induce toxic effects as well, points out the need for a systematic approach towards their evaluation before efficient introduction to wound care (or other fields of medicine) [49]. In recent years, extensive research has been carried out in the area of wound healing and management through

The following subchapters review the key details related to the potential use of medicinal

When we describe the beneficial effects of plant-derived molecules on human health, mostly it is the secondary plant metabolites, producing pharmacological and/or toxicological effects, that we are discussing [48]. Secondary metabolites are produced within the plants and are regarded as by-products of biochemical reactions in the plant cells. As such, these molecules are not part of any crucial daily functioning of the plant, hence are not important for the plants main biosynthetic and metabolic routes that yield products with major significance for the plant growth and/or development [50]. Although this means that these molecules are not key to the plants basic functions, this does not mean that they do not importantly

**4.1. Groups of plant-derived molecules with beneficial effects on wound healing**

pathologic actions of oxidants, including the wound healing [26].

that were already proven for the mentioned use.

plant-derived medicinal products [38].

plants in wound healing.

**4. Plants with potential use in wound healing**

An important complication related to wound treatment and healing is infection. Infections are known to significantly increase the treatment costs of wound care [18], which are also the reason that different strategies are being developed for their prevention [19]. Due to the impact of primary and secondary infections on the wound healing, which increase local inflammation, and hence lead to significant tissue destruction, prevention of their occurrence remains one of the main targets of wound dressing development [20]. An ideal medicine for the prevention of wound infection should therefore have antimicrobial activities, while also stimulating the body's natural immune system without damaging the surrounding healthy tissue [21].

Most wounds induce some level of pain sensation. Pain relates to patient's discomfort, release of stress hormones and often reduces the patients' overall quality of life. Hindered mobility and psychological issues connected with pain-induced stress lead to a less effective wound healing. According to McGuire et al. [22], chronic pain lowers the patients' capability of healing, thereby prolonging the overall recovery process [23]. Suitable and effective pain management can lead to an earlier release from the hospital, stress reduction and a general better reintegration into the community. All mentioned lead to facilitation of wound healing, while at the same time minimizing the risk for development of chronic pain, and finally in lowered treatment costs [24].

**Figure 2.** A diagram showing the most important beneficial properties that are desired in wound treatment (and some of the already known plants used in traditional medicine for this purpose). Anti-inflammatory: *Achillea* [28], *Aloe vera* [29], *Avena* [30], *Azadirachta indica* [31], *Calendula officinalis* [32], *Cedrus deodara* [33], *Chamomilla recutita* [34], *Commiphora myrrha* [35], *Curcuma longa* [36], *Echinacea* [37], *Euphorbia hirta* [38], *Hypericum perforatum* [39], *Rosmarinus officinalis* [40]. Antimicrobial: *Achillea* [28], *Angelica sinensis* [41], *Azadirachta indica* [31], *Calendula officinalis* [32], *Cedrus deodara* [33], *Chamomilla recutita* [34], *Commiphora myrrha* [35], *Curcuma longa* [36], *Echinacea* [42], *Hypericum perforatum* [43]. Analgesic: *Angelica sinensis* [41], *Commiphora myrrha* [44], *Curcuma longa* [36], *Euphorbia hirta* [38], *Hypericum perforatum* [43]. Antioxidant: *Chamomilla recutita* [34], *Ginkgo biloba* [45].

Part of the inflammation phase of wound healing causes also a coordinated influx of neutrophils to the wound site. One of the actions of neutrophils is also the activation of the so-called 'respiratory burst', which leads to productions of free radicals [25]. These produce oxidative stress that results in lipid peroxidation, DNA damage, and enzyme inactivation (e.g. free-radical scavenger enzymes and others), even those whose main activity is to limit the effects of reactive oxygen species (ROS). Considering the above mentioned, it is clear that antioxidants may be of therapeutic use in several diseases that are connected with potential pathologic actions of oxidants, including the wound healing [26].

Apart from the above-mentioned wound healing aiding activities, others are also reported in literature, e.g. the astringent activity, stimulated epithelisation and effective hydration of the wound site [27]. The most important properties of plant-derived medicines that are beneficial for the wound healing process are depicted in **Figure 2** together with some examples of plants that were already proven for the mentioned use.
