| dc.description.abstract | Various previous studies have shown that shikonin, which is derived from medicinal plant Lithospermum erythrorhizon, can display diverse pharmacological beneficial effects or strong and specific bioactivities, e.g., in wound healing-, anti-inflammatory- and anti-tumor bioactivities. The aim of my present experimental study is to address whether and how shikonin may be involved in the regulation of vascular permeability in mouse skin tissues. Shikonin-treated skin samples originating from different organs, including ear, abdominal and leg skin of test mice, were collected at different time points tested, and protein expression levels of matrix metalloproteinases (MMP) and E-cadherin determined. Activity of vascular permeability was investigated by measuring the level of extravasation of Evans blue dye from blood vessels by Miles assay; also determined by the expression levels of MMP-2, MMP-9 and E-cadherin. MMP-2 and MMP-9 are two representative members of the MMPs family that play a critical role in regulation of vascular permeability. As revealed by Miles assay, shikonin exhibited high activity in extravasation of Evans blue dye from blood vessels to the adjacent dermal tissues, clearly indicating its leakage. Shikonin-treated skins samples showed higher protein expression levels for MMP-9 and MMP-2 when compared with vehicle control samples. To further evaluate whether shikonin can confer pro-inflammatory effect on skin tissue, the expression level of IL-1β and IL-6 were determined. High levels of IL-1β and IL-6 were found in shikonin-treated skins. Together, our data indicate that topical application of shikonin can effectively enhance vascular permeability in test skin, suggesting that shikonin may be clinically applicable as a potential adjuvant for use on improving the efficiency and specificity of drug delivery into adjacent tissues.
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