A preliminary experimental study of venoactive compounds on human lymphatic endothelial cells: cellular response and therapeutic potential.

PURPOSE: Lymphedema is a common complication following surgical procedures, particularly in breast cancer patients. However, no effective medical treatment has been clearly established. Venoactive compounds (venoactive drugs, VADs) are frequently used as an alternative option, despite limited supporting evidence. This study aimed to evaluate their potential therapeutic role in lymphedema.

METHODS

Human lymphatic endothelial cells (HLECs) were used to assess the effects of diosmin, calcium dobesilate, and Vitis vinifera extract. Cell viability was evaluated using the MTT assay to determine non-cytotoxic concentrations. Lymphangiogenesis was assessed using Transwell migration and Matrigel-based tube formation assays (Corning). Western blot analysis was performed to examine the activation of protein kinase B (AKT), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways.

RESULTS

Treatment with VADs showed an overall tendency to suppress cell migration compared to the control. On the other hand, there was no significant difference in the tube formation. Western blot analysis revealed that Vitis vinifera extract significantly inhibited the activation of AKT, ERK, and p38 MAPK pathways. Diosmin increased p38 activation without affecting AKT or ERK, while calcium dobesilate did not induce any significant changes in these signaling pathways.

CONCLUSION

VADs did not directly promote lymphangiogenesis in HLECs. Their therapeutic effects in lymphedema may instead be mediated by microvascular stabilization through anti-inflammatory, antioxidant, and permeability-reducing mechanisms. Further experimental and clinical studies are needed to validate these findings.