**1. Introduction**

A wound is disruption of barrier function of the skin which may result from a physical or chemical injury. Depending on time taken for healing process, it can be categorized as simple, acute wound and chronic wound. The human body has the potential to initiate wound healing process in order to replace the damaged cellular structures and tissue layers. This complex process is comprises of sequence of events starting from homeostasis, inflammation, proliferation/granulation leading to remodeling/maturation [1].

Acute wounds are characterized by minimal localized microbial infection and scab formation. Infiltration of immune cells leads to re-epithelialization, angiogenesis and fibroblast migration. If the immune system is unable to control the infection, microbial biofilm is formed leading to impaired wound healing. Chronic wounds are characterized by increased inflammatory process, lower oxygenation of the deep tissues due to fibrin cuffs formation, fibroblast senescence, impaired angiogenesis and re-epithelialization. Most chronic wounds are ulcers that are associated with ischemia, diabetes mellitus, venous stasis disease, or pressure [2, 3].

Wound care is a million-dollar global industry which determines the appropriate treatment to promote wound healing with minimal infections [4]. Several aspects of wound healing are encompassed in the management including, but not limiting to maintaining optimum moist environment at the wound site, infection control, treatments for deep seated tissue regeneration using stem cell therapy [4, 5]. Despite medical advancements in wound care, there is a mounting demand for alternative treatments from the clinical and economic perspective. It has been reported that chronic wounds affect 6.5 million people in the USA, and costs over US \$25 billion each year. Alarmingly, the burden of chronic wounds is expected to rise due to global increases in vascular diseases, diabetes, obesity, metabolic syndrome, and the general aging of the population [6]. In ancient times, tribal people used plants to cure wounds. Even now, plants are considered as huge source of novel bioactive agents. It has been found that at present there are more than 450 plant species being extensively used for their wound healing ability, yet the search for novel wound healing agents from natural resources with minimal scaring is never ending [7].

There are numerous medicaments available to augment skin wound healing, disinfectants like ethyl alcohol, iodine, ether, ointments containing antibiotics and steroid hormones. Iodine based preparations and silver releasing agents have been used as antimicrobial agents to treat infected wounds. They target bacteria at cell membrane, cytoplasmic organelle, and nucleic acid level, thus minimizing bacterial resistance [8]. They can be used either alone or in conjunction with systemic antibiotics. Advanced silver dressings, aim to deliver sustained doses of silver to the wound [9, 10]. In addition to the microbicidal effect of silver on common wound contaminants, silver may also be effective against resistant strains like methicillin resistant *Staphylococcus aureus* (MRSA). Zinc, an antioxidant, used in a paste bandage is useful in treating infected leg ulcers. Phenytoin, applied topically, promotes wound healing by inhibiting the enzyme collagenase. It is effective in some low grade pressure ulcers and trophic ulcers due to leprosy. The possibility of systemic absorption and toxicity has limited its use. Analgesics are in great demand for treatment of ulcers. They may comprise of simple analgesics like NSAIDs or strong analgesics like opiates in case of severe pain. Tricyclic antidepressants (such as amitriptyline) or antiepileptic drugs (such as gabapentin) are drugs of choice for ulcers associated with neuropathic pain [11]. These agents provide preliminary relief but interfere with the normal healing process. They injure not only invading foreign organisms but also normal body cells. They can lead to emergence of resistant bacterial infection and hypersensitivity reactions. From ancient times, various natural substances have been widely used for wound healing [12].

The polyphenols in plant extracts are capable of neutralizing free radicals by combining with active oxygen [13]. A stable phenoxyl radical is formed when a polyphenolic compound combines with free radicals formed during the metabolic process. Superoxide, hydroxyl, lipid peroxyl, nitric oxide radicals, and peroxynitrites are the most common free radicals with which polyphenolic compounds usually combine. In wounds there is a high oxidative stress due to the activation of platelets, neutrophils, macrophages, lymphocytes and fibroblasts. The concentration of reactive oxygen species varies at different time points of the healing

process [3]. This is further enhanced by infection from microbes. In such conditions, plant based polyphenol may assist in the healing process by modulating the concentrations of reactive oxygen species [14].

In case of burn wounds, coagulative necrosis is quite predominant resulting in scar formation after repair. Macrophages migrate to the injured area to kill invading organisms and produce cytokines that recruit other inflammatory cells that are responsible for cascade of inflammatory reactions. Angiogenesis at the injured area is vital in wound healing process. Moreover, growth factors and cytokines play crucial role in wound-healing process [15, 16]. Hypoxia induces cytokine and growth factor production from macrophages, keratinocytes, and fibroblasts. These include platelet-derived growth factor (PDGF), transforming growth factor (TGF-β), vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and endothelin-1. They in turn promote cell proliferation, migration, chemotaxis and angiogenesis in wound healing [17]. Although, hypoxia stimulates wound healing such as the release of growth factors and angiogenesis, still oxygen is needed to sustain the healing process [18].

Hence, burn wound healing is a multiple step process, involving inflammatory phases such as monocyte migration, cytokine production, growth factors and angiogenesis during re-epithelialization. Preliminary experiments, reveal that total ginseng saponins isolated from Red Ginseng roots accelerated burn wound healing in mice. There are significant number of indications on wound healing effects of ginsenosides with diverse associated mechanisms, one such report is on skin regeneration by the ginsenoside Rd (discussed later in the chapter) isolated from ginseng leaves. GinsenosideRb1 promotes burn wound healing process by enhancing angiogenesis [19].
