Cornus sanguinea Fruits: a Source of Antioxidant and Antisenescence Compounds Acting on Aged Human Dermal and Gingival Fibroblasts.

Five new compounds, a flavonol glycoside ( 1: ), a megastigmane ( 2: ), 2 cyclohexylethanoids ( 3, 4: ), and a phenylethanoid derivative ( 5: ), together with 15 known compounds ( 6: - 20: ) including flavonoid glycosides, cyclohexylethanoids, and phenolic compounds, have been isolated from Cornus sanguinea drupes. All the structures have been determined by 1D and 2D NMR spectroscopic analysis and mass spectrometry data. The antioxidant capability of the most representative isolated compounds was evaluated in the hydrogen peroxide (H2O2)-induced premature cellular senescence model of human dermal and gingival fibroblasts. Several derivatives counteracted the increase of reactive oxigen species (ROS) production in both cellular models. Among the most promising, compounds 8, 14: , and 20: were able to counteract cell senescence, decreasing the expression of p21 and p53. Furthermore, compound 14: decreased the expression of inflammatory cytokines (IL-6) in both cell models and counteracted the decrease of collagen expression induced by the H2O2 in dermal human fibroblasts. These data highlight the anti-aging properties of several isolated compounds from C. sanguinea drupes, supporting its possible use in the cure of skin or periodontitis lesions.

Antioxidant Activity of Compounds Isolated from Elaeagnus umbellata Promotes Human Gingival Fibroblast Well-Being.

Four new triterpenoid bidesmosidic saponins (1-4) and a sesquiterpenoid glucoside (5), together with nine known phenolic compounds (6-14), were isolated from the fruits of Elaeagnus umbellata. Their structures were elucidated using 1D and 2D NMR spectroscopy and mass spectrometry data. The antioxidant capability of the isolated compounds was evaluated in human gingival fibroblasts. Compound 6 decreased ROS production and promoted cell proliferation. It also counteracted the cell cycle blockade induced by a low concentration of H2O2 decreasing the expression of p21 and CDKN2A (p16INK4A). Compound 6 decreased the expression of inflammatory cytokines (IL-6 and IL-8) in response to inflammatory stimuli, supporting its possible use in periodontitis lesions.

Negative effects of a high tumour necrosis factor-α concentration on human gingival mesenchymal stem cell trophism: the use of natural compounds as modulatory agents.

BACKGROUND: Adult mesenchymal stem cells (MSCs) play a crucial role in the maintenance of tissue homeostasis and in regenerative processes. Among the different MSC types, the gingiva-derived mesenchymal stem cells (GMSCs) have arisen as a promising tool to promote the repair of damaged tissues secreting trophic mediators that affect different types of cells involved in regenerative processes. Tumour necrosis factor (TNF)-α is one of the key mediators of inflammation that could affect tissue regenerative processes and modify the MSC properties in in-vitro applications. To date, no data have been reported on the effects of TNF-α on GMSC trophic activities and how its modulation with anti-inflammatory agents from natural sources could modulate the GMSC properties. METHODS: GMSCs were isolated and characterized from healthy subjects. The effects of TNF-α were evaluated on GMSCs and on the well-being of endothelial cells. The secretion of cytokines was measured and related to the modification of GMSC-endothelial cell communication using a conditioned-medium method. The ability to modify the inflammatory response was evaluated in the presence of Ribes nigrum bud extract (RBE). RESULTS: TNF-α differently affected GMSC proliferation and the expression of inflammatory-related proteins (interleukin (IL)-6, IL-10, transforming growth factor (TGF)-ß, and cyclooxygenase (COX)-2) dependent on its concentration. A high TNF-α concentration decreased the GMSC viability and impaired the positive cross-talk between GMSCs and endothelial cells, probably by enhancing the amount of pro-inflammatory cytokines in the GMSC secretome. RBE restored the beneficial effects of GMSCs on endothelial viability and motility under inflammatory conditions. CONCLUSIONS: A high TNF-α concentration decreased the well-being of GMSCs, modifying their trophic activities and decreasing endothelial cell healing. These data highlight the importance of controlling TNF-α concentrations to maintain the trophic activity of GMSCs. Furthermore, the use of natural anti-inflammatory agents restored the regenerative properties of GMSCs on endothelial cells, opening the way to the use and development of natural extracts in wound healing, periodontal regeneration, and tissue-engineering applications that use MSCs.