Positive Health Online

Abstract

XU and COLLEAGUES, 1. The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institutet and Department of Endocrinology, Diabetes and Metabolism Karolinska Hospital, SE-171 76 Stockholm, Sweden; 2. Department of Oncology-Pathology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland; 4. The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institutet and Department of Endocrinology, Diabetes and Metabolism Karolinska Hospital, SE-171 76 Stockholm, Sweden. michael.tekle@ki.se conducted a study to investigate the effects of mono-epoxy-tocotrienol-α on in vitro and in vivo wound healing models as well as its effects on mitochondrial function.

Background

Diabetes mellitus is characterized by hyperglycaemia and capillary hypoxia that causes excessive production of free radicals and impaired antioxidant defence, resulting in oxidative stress and diabetes complications such as impaired wound healing. We have previously shown that modified forms of tocotrienols possess beneficial effects on the biosynthesis of the mevalonate pathway lipids including increase in mitochondrial CoQ.

Methodology

The aim of this study is to investigate the effects of mono-epoxy-tocotrienol-α on in vitro and in vivo wound healing models as well as its effects on mitochondrial function. Gene profiling analysis and gene expression studies on HepG2 cells and human dermal fibroblasts were performed by microarray and qPCR, respectively. In vitro wound healing using human fibroblasts was studied by scratch assay and in vitro angiogenesis using human dermal microvascular endothelial cells was studied by the tube formation assay. In vivo wound healing was performed in the diabetic db/db mouse model. For the study of mitochondrial functions and oxygen consumption rate Seahorse XF-24 was employed.

Results

In vitro, significant increase in wound closure and cell migration (p<0.05) both in normal and high glucose and in endothelial tube formation (angiogenesis) (p<0.005) were observed. Microarray profiling analysis showed a 20-fold increase of KIF26A gene expression and 11-fold decrease of lanosterol synthase expression. Expression analysis by qPCR showed significant increase of the growth factors VEGFA and PDGFB. The epoxidated compound induced a significantly higher basal and reserve mitochondrial capacity in both HDF and HepG2 cells. Additionally, in vivo wound healing in db/db mice, demonstrated a small but significant enhancement on wound healing upon local application of the compound compared to treatment with vehicle alone.

Conclusion

Mono-epoxy-tocotrienol-α seems to possess beneficial effects on wound healing by increasing the expression of genes involved in cell growth, motility and angiogenes as well as on mitochondrial function.

References

Xu C1, Bentinger M1, Savu O1, Moshfegh A2, Sunkari V1, Dallner G1, Swiezewska E3, Catrina SB1, Brismar K1, Tekle M4. Mono-epoxy-tocotrienol-α enhances wound healing in diabetic mice and stimulates in vitro angiogenesis and cell migration. J Diabetes Complications; 31(1):4-12. doi: 10.1016/j.jdiacomp.2016.10.010 . Epub Oct 18 2016. Jan 2017.