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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 148297, 11 pages
Research Article

Enhancement of Lymphangiogenesis In Vitro via the Regulations of HIF-1 Expression and Nuclear Translocation by Deoxyshikonin

1Department of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan
2Department of Biopharmacy, Faculty of Pharmacy, Srinakharinwirot University, Nakhonnayok 26120, Thailand

Received 11 January 2013; Revised 19 March 2013; Accepted 21 March 2013

Academic Editor: Ken Yasukawa

Copyright © 2013 Orawin Prangsaengtong et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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-1α mRNA level, HIF-1α protein level, and the accumulation of HIF-1α in the nucleus. Knockdown of the HIF-1α gene by transfection with siHIF-1α 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-1α knockdown cells. This indicated that deoxyshikonin induction of VEGF-C mRNA expression and cord formation in HMVEC-dLy on Matrigel occurred mainly via HIF-1α 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-1α. The findings suggest that deoxyshikonin may be a new drug candidate for wound healing and treatment of lymphatic diseases.