Plasma cupping induces VEGF expression in skin cells through nitric oxide-mediated activation of hypoxia inducible factor 1

Despite a long history, the clinical efficacy of cupping therapy is still under debate. This is likely due to the lack of direct evidence for the biological actions of cupping, since the short exposure of cells to vacuum condition rarely has affects cellular activity. In this study, the medicinal properties of a recent medical technology, non-thermal plasma, were added to classical cupping and designated as ‘plasma cupping’ (PC). In our results, the plasma-generating efficacy was increased under a cupping-like semi-vacuum condition (410 Torr) rather than normal atmospheric pressure (760 Torr). Notably, while cupping rarely affects the angiogenic factor vascular-endothelial growth factor (VEGF)-A, the PC treatment on HaCaT human keratinocytes significantly induced the expression of VEGF-A. The increased expression of the VEGF-A gene after the PC treatment was expected to be a result of PC-mediated ERK protein activation. The PC-mediated activation of ERK was essential for the activity of hypoxia inducible factor (HIF) 1 alpha, which is responsible for the PC-mediated expression of VEGF-A. The PC mediated increase of NO in the media was thought as a main reason for the elevated HIF-1 protein activity. In addition to the angiogenesis-promoting action of PC, it also showed anti-inflammatory activity by reducing TNF-α-mediated IL-1β and IL-6 expression. Taken together, this study indicates the potential for PC that could enhance the clinical efficacy of cupping by adding the effects of non-thermal plasma to traditional cupping.