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The objectives of this study were to determine the effects of deoxyshikonin on lymphangiogenesis. Deoxyshikonin enhanced the ability of human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) to undergo time-dependent  in vitro  cord formation. Interestingly, an opposite result was observed in cells treated with shikonin. The increased cord formation ability following deoxyshikonin treatment correlated with increased VEGF-C mRNA expression to higher levels than seen for VEGF-A and VEGF-D mRNA expression. We also found that deoxyshikonin regulated cord formation of HMVEC-dLy by increasing the HIF-1  α   mRNA level, HIF-1  α   protein level, and the accumulation of HIF-1  α   in the nucleus. Knockdown of the HIF-1  α   gene by transfection with siHIF-1  α   decreased VEGF-C mRNA expression and cord formation ability in HMVEC-dLy. Deoxyshikonin treatment could not recover VEGF-C mRNA expression and cord formation ability in HIF-1  α   knockdown cells. This indicated that deoxyshikonin induction of VEGF-C mRNA expression and cord formation in HMVEC-dLy on Matrigel occurred mainly via HIF-1  α   regulation. We also found that deoxyshikonin promoted wound healing  in vitro  by the induction of HMVEC-dLy migration into the wound gap. This study describes a new effect of deoxyshikonin, namely, the promotion of cord formation by human endothelial cells via the regulation of HIF-1  α  . The findings suggest that deoxyshikonin may be a new drug candidate for wound healing and treatment of lymphatic diseases.

evidence-based complementary and alternative medicine

Enhancement of Lymphangiogenesis<i>In Vitro</i>via the Regulations of HIF-1<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi mathvariant="bold-italic">α</mml:mi></mml:mrow></mml:math>Expression and Nuclear Translocation by Deoxyshikonin

Enhancement of LymphangiogenesisIn Vitrovia the Regulations of HIF-1αExpression and Nuclear Translocation by Deoxyshikonin