Abstract
Centella asiatica herbs have been prescribed as a traditional medicine for wound healing in China and Southeast Asia for a long time. They contain many kinds of triterpenoid compounds, mainly including glycosides (asiaticoside and madecassoside) and corresponding aglycones (asiatic acid and madecassic acid). To identify which is the major active constituent, a comprehensive and comparative study of these compounds was performed. In vitro, primary human skin fibroblasts, originating from healthy human foreskin samples, were treated with various concentrations of asiaticoside, madecassoside, asiatic acid, and madecassic acid, respectively. Cell proliferation, collagen synthesis, MMP-1/TIMP-1 balance, and TGF-β/Smad signaling pathway were investigated. In vivo, mice were orally administered with the four compounds mentioned above for two weeks after burn injury. The speed and quality of wound healing, as well as TGF-β 1 levels in skin tissues, were examined. Interestingly, in contrast to prevalent postulations, asiaticoside and madecassoside themselves, rather than their corresponding metabolites asiatic acid and madecassic acid, are recognized as the main active constituents of C. asiatica herbs responsible for burn wound healing. Furthermore, madecassoside is more effective than asiaticoside (P = 0.0446 for procollagen type III synthesis in vitro, P = 0.0057 for wound healing speed, and P = 0.0491 for wound healing pattern in vivo, correspondingly).
Highlights
Burn injury is a dermal or other organic tissue injury mainly caused by thermal or chemical insults, and includes scalds, contact, and flame burns [1]
Aisaticoside, madecassoside, asiatic acid, and madecassic acid were reported as major constituents of C. asiatica with pharmacological activities [23]
Previous independent studies have disclosed that C. asiatica extract, together with two glycosides, namely asiaticoside and madecassoside, could facilitate wound healing either induced by surgical or thermal injuries [13, 15, 24]
Summary
Burn injury is a dermal or other organic tissue injury mainly caused by thermal or chemical insults, and includes scalds, contact, and flame burns [1]. According to the report presented by World Health Organization (WHO) at the year 2002, it was estimated an annual casualty of 330,000 deaths was, directly or indirectly, related to burn injury [2]. After burn injury, skin responds to the affliction with a complex, well-orchestrated, wound healing process. As a self-limited process, normal wound healing ends up with a remodeling phase characterized by apoptosis of myofibroblasts and macrophages, secretion of matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinases (TIMPs) from fibroblasts, which recovers the texture and strength close to normal state [5]
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