naphthoquinones and Varicose-Ulcer

Alkannin-based pharmaceutical formulations for improving wound healing have been on the market for several years. However, detailed molecular mechanisms of their action have yet to be elucidated. Here, we investigated the potential roles of AAN-II in improving the healing of pressure-induced venous ulcers using a rabbit model generated by combining deep vein thrombosis with a local skin defect/local skin defect. The extent of healing was evaluated using hematoxylin and eosin (HE) or vimentin staining. Rabbit skin fibroblasts were cultured for AAN-II treatment or TGFB1-sgRNA lentivirus transfection. ELISA was used to evaluate the levels of various cytokines, including IL-1β, IL-4, IL-6, TNF-α, VEGF, bFGF, TGF-β and PDGF. The protein levels of TGF-β sensors, including TGF-β, Smad7 and phosphor-Smad3, and total Smad3, were assayed via western blotting after TGF-β knockout or AAN-II treatment. The results show that, for this model, AAN-II facilitates ulcer healing by suppressing the development of inflammation and promoting fibroblast proliferation and secretion of proangiogenic factors. AAN-II enhances the activation of the TGF-β1-Smad3 signaling pathway during skin ulcer healing. In addition, the results demonstrate that AAN-II and TGF-β have synergistic effects on ulcer healing. Our findings indicate that AAN-II can promote healing of pressure-induced venous skin ulcers via activation of TGF-β-Smad3 signaling in fibroblast cells and provide evidence that could be used in the development of more effective treatments.

Topics: Animals; Boraginaceae; Disease Models, Animal; Female; Naphthoquinones; Pressure; Rabbits; Signal Transduction; Smad3 Protein; Transforming Growth Factor beta1; Varicose Ulcer; Wound Healing

From the roots of Alkanna tinctoria Tausch, the alkannin esters of the following acids were isolated and identified: beta,beta-dimethylacrylic acid, beta-acetoxy-isovaleric acid, isovaleric acid, and angelic acid. These esteric pigments showed excellent wound healing properties in a clinical study on 72 patients with ulcus cruris.

Topics: Anti-Bacterial Agents; Humans; Naphthoquinones; Plant Extracts; Plants, Medicinal; Salmonella; Varicose Ulcer; Wound Healing