To Investigate the Functions of Shikonin and Its Derivatives in Applied Age-Related Macular Degeneration and Wound Healining

Shikonin is a major component of “Zicao” (the dried root extract of Lithospermum euchroma, Boraginaceae) and is commonly used in China and Japan to treat cut or burn wound in old ages. In our grant, we have already performed several preliminary experiments using live animal and human fibroblast cell and we observed a number beneficial properties of shikonin on wound healing, possibly involving ERK1/2, PAI-1, MMP-1, Procollagen type I and TGF-β regulation. We have also had an obvious inhibition of 5-FU induced mucositis in hamster model. Other than anti-inflammation and anti-mucositis, countless literatures have shown that shiknon holds anti-angiogenesis and anti-cancer effects. Based on the discoveries above, we have proposed a three year grant, hoping to further expose the pharmlogical effects of shikonin. We divided the studies into three major components over three years; 1) How shikonin affects angiogenesis using a well-established rat vascular retina model to study the potential effects of shikonin on suppressing age-related macular degeneration; 2) How shikonin treatment reduces the occurences of mucositis in both vitro (IMR 90 cells) and vivo (5-FU induced mucositis in hamster); 3) To investigate how shikonin promotes wound healing in both vitro (CCD-966SK cells) and vivo (rat animal model). These studies will help us to better understand the multiple beneficial pharmacological effects, and further apply to possible clinical applications for shikonin.