## 6 Therapeutic Actions of Madecassoside and Other Major Compounds in _C. asiatica_
### Skin Related Disease or Wound  
_C. asiatica_ has been used extensively in traditional medicines for treating skin related wounds and diseases, such as ulcerous skin abnormalities, lupus, scleroderma, leprosy [74]; a small number of studies have suggested that the beneficial effects are due to macdecassoside, the most abundant triterpene present in extracts of _C. asiatica_[75]. Many studies suggested that macdecassoside is beneficial in a variety of skin disorders, in which it may prevent skin aging and promote wound healing, as well as exerting anti-inflammatory and anti-posoriasis effects [76]. These effects of macdecassoside may be due to its ability to protect against lipid peroxidation, and intensify collagen synthesis and expression while stimulating angiogenesis [77]. The most widely studied effects of _C. asiatica_ extract and madecassoside have been in the context of burn wound healing. Burn wounds are categorized as tissue injury caused by external triggers, such as heat, chemicals, radiation and electricity [74]. Burn wounds could be classified into three degrees, predominantly based on the complexity of the wound incurred; these are superficial (first degree), partial thickness (second degree) and full thickness (third degree). Burn wound healing is complex, comprising an array of processes. It commences with inflammation that interrupts blood vessels and stimulates blood constituents to be released to the target area to stimulate re-epithelialization; followed by the formation of granulation tissue consisting of macrophages and fibroblasts that are responsible for extracellular matrix recovery; neo-vascularization towards the target area; in addition to mitogenic stimulation and migration of cells of endothelial origin. Finally, communication between extracellular matrix cells and cytokines results in wound contraction [74]. In rats, madecassoside and asiaticoside were reported to possess wound healing properties [74]. Madecassoside was shown to augment inflammatory cell infiltration, and to nurture re-epithelialization to achieve an almost complete wound closure with an improved healing pattern in the burned skin on mice [78]. Furthermore, in vitro studies have demonstrated the ability of madecassoside to promote type I and III collagen synthesis and to stimulate the proliferation of cultured human fibroblasts [78]; similar findings were also reported for asiaticoside [79]. Madecassoside was shown to augment endothelial cell growth in rat aortic rings in vitro, and to markedly increase angiogenesis in mouse burn wounds; it was hypothesized that madecassoside expedites burn wound healing through increased antioxidative activity, enriched collagen synthesis and angiogenesis [78]. In a separate study, madecassoside was shown to protect human umbilical vein endothelial cells (HUVECs) against hydrogen peroxide-induced lipid peroxidation and apoptosis via protecting the mitochondrion membranes, and inhibiting the activation of caspase-3 and p38 MAPK [80]. Similar studies have also been conducted to test the efficacy of asiaticoside in wound healing. Asiaticoside treatment increased migration rates and initial attachment of skin cells, while promoting normal human dermal fibroblast proliferation [81]. Asiaticoside also exhibited significant wound healing activity in normal as well as delayed healing models [82]. A study suggested that the enhancement of burn wound healing by asiaticoside could be due to the promotion of angiogenesis as a result of stimulation of the production of vascular endothelial growth factor (VEGF), caused by an increased expression of monocyte chemoattractant protein-1 (MCP-1) in keratinocytes, even at very low doses of asiaticoside (10 pg, 1 ng and 100 ng per mouse) [83]. Furthermore, the augmented healing produced by asiaticoside could be due to its capacity to enhance tissue antioxidant levels [84]; this study also suggested that asiaticoside would be helpful in wound repair only if applied during the active/initial phase of healing [84].