P Di Tomo1, S Di Silvestre1, V G P Cordone1, A Giardinelli1, B Faricelli2, C Pipino1, P Lanuti2, T Peng3, G Formoso2, D Yang3, A Arduini4, F Chiarelli5, A Pandolfi1, N Di Pietro6. 1. Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University, Chieti, Italy; Aging Research Center, Ce.S.I., "Gabriele d'Annunzio" University Foundation, Chieti, Italy. 2. Department of Medicine and Aging Sciences, "G. d'Annunzio" University, Chieti, Italy; Aging Research Center, Ce.S.I., "Gabriele d'Annunzio" University Foundation, Chieti, Italy. 3. Morningside Laboratory for Chemical Biology and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, PR China. 4. CoreQuest Sagl, Manno, Ticino, Switzerland. 5. Department of Medicine and Aging Sciences, "G. d'Annunzio" University, Chieti, Italy. 6. Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University, Chieti, Italy; Aging Research Center, Ce.S.I., "Gabriele d'Annunzio" University Foundation, Chieti, Italy. Electronic address: n.dipietro@unich.it.
Abstract
BACKGROUND AND AIMS: Diabetes mellitus is associated with inflammatory endothelial activation and increased vascular leukocyte adhesion molecule expression, both playing a prominent role in the development of vascular complications. Centella asiatica (CA) and Lipoic Acid (LA) have shown anti-inflammatory and anti-oxidant properties in a variety of experimental models; however, their action on human umbilical vein endothelial cells (HUVECs), chronically exposed to hyperglycemia and pro-inflammatory environment during pregnancy, is still unknown. METHODS AND RESULTS: In HUVECs from umbilical cords of gestational diabetic (GD) or healthy (C) women, both CA and LA affected tumor necrosis factor-α (TNF-α)-induced inflammation, being associated with a significant decrease in vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression (western blot) and exposure (flow cytometry), as well as monocyte-HUVECs interaction (adhesion assay). Notably, this was associated with a significant reduction of an index of nitro-oxidative stress, such as the intracellular peroxynitrite levels (fluorescence detection by cytometric analysis), Mitogen-Activated Protein kinase (p44/42 MAPK) expression/phosphorylation levels and Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB p65) cytoplasm-nucleus translocation (flow cytometry). Overall our results indicate that both CA and LA used separately, and even better when combined, are effective to reduce the inflammatory response in TNF-α-treated HUVECs. Notably, this was more significant in GD than in C-HUVECs and also evident at baseline. CONCLUSION: In conclusion, our in vitro study demonstrates that both CA and LA, or a combination thereof, are able to mitigate the potentially dangerous effects on the endothelium of chronic exposure to hyperglycemia in vivo.
BACKGROUND AND AIMS: Diabetes mellitus is associated with inflammatory endothelial activation and increased vascular leukocyte adhesion molecule expression, both playing a prominent role in the development of vascular complications. Centella asiatica (CA) and Lipoic Acid (LA) have shown anti-inflammatory and anti-oxidant properties in a variety of experimental models; however, their action on human umbilical vein endothelial cells (HUVECs), chronically exposed to hyperglycemia and pro-inflammatory environment during pregnancy, is still unknown. METHODS AND RESULTS: In HUVECs from umbilical cords of gestational diabetic (GD) or healthy (C) women, both CA and LA affected tumornecrosis factor-α (TNF-α)-induced inflammation, being associated with a significant decrease in vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression (western blot) and exposure (flow cytometry), as well as monocyte-HUVECs interaction (adhesion assay). Notably, this was associated with a significant reduction of an index of nitro-oxidative stress, such as the intracellular peroxynitrite levels (fluorescence detection by cytometric analysis), Mitogen-Activated Protein kinase (p44/42 MAPK) expression/phosphorylation levels and Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB p65) cytoplasm-nucleus translocation (flow cytometry). Overall our results indicate that both CA and LA used separately, and even better when combined, are effective to reduce the inflammatory response in TNF-α-treated HUVECs. Notably, this was more significant in GD than in C-HUVECs and also evident at baseline. CONCLUSION: In conclusion, our in vitro study demonstrates that both CA and LA, or a combination thereof, are able to mitigate the potentially dangerous effects on the endothelium of chronic exposure to hyperglycemia in vivo.
Authors: Mario Bonomini; Sara Di Silvestre; Pamela Di Tomo; Natalia Di Pietro; Domitilla Mandatori; Lorenzo Di Liberato; Vittorio Sirolli; Francesco Chiarelli; Cesare Indiveri; Assunta Pandolfi; Arduino Arduini Journal: Drug Des Devel Ther Date: 2016-11-28 Impact factor: 4.162