Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Department of Pharmacy, University "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Int J Mol Sci. 2023 Feb 7;24(4):3276. doi: 10.3390/ijms24043276.
Recently, there has been an increasing interest in finding new approaches to manage oral wound healing. Although resveratrol (RSV) exhibited many biological properties, such as antioxidant and anti-inflammatory activities, its use as a drug is limited by unfavorable bioavailability. This study aimed to investigate a series of RSV derivatives (-) with better pharmacokinetic profiles. At first, their cytocompatibility at different concentrations was tested on gingival fibroblasts (HGFs). Among them, derivatives and significantly increased cell viability compared to the reference compound RSV. Thus, and were investigated for cytotoxicity, proliferation, and gene expression in HGFs, endothelial cells (HUVECs), and oral osteoblasts (HOBs), which are the main cells involved in oral wound healing. For HUVECs and HGFs, the morphology was also evaluated, while for HOBs ALP and mineralization were observed. The results showed that both and did not exert negative effects on cell viability, and at a lower concentration (5 µM) both even significantly enhanced the proliferative rate, compared to RSV. The morphology observations pointed out that the density of HUVECs and HGFs was promoted by and (5 µM) and mineralization was promoted in HOBs. Moreover, and (5 µM) induced a higher eNOS mRNA level in HUVECs, higher COL1 mRNA in HGFs, and higher OCN in HOBs, compared to RSV. The appreciable physicochemical properties and good enzymatic and chemical stability of and , along with their promising biological properties, provide the scientific basis for further studies leading to the development of RSV-based agents useful in oral tissue repair.
最近，人们越来越关注寻找新的方法来管理口腔伤口愈合。虽然白藜芦醇 (RSV) 表现出许多生物特性，如抗氧化和抗炎活性，但由于其生物利用度不理想，其作为药物的应用受到限制。本研究旨在研究一系列具有更好药代动力学特征的 RSV 衍生物 (-)。首先，在不同浓度下，它们在牙龈成纤维细胞 (HGFs) 上的细胞相容性进行了测试。其中，衍生物 和 与参比化合物 RSV 相比，显著提高了细胞活力。因此， 和 对 HGFs、内皮细胞 (HUVECs) 和口腔成骨细胞 (HOBs) 的细胞毒性、增殖和基因表达进行了研究，这些细胞是参与口腔伤口愈合的主要细胞。对于 HUVECs 和 HGFs，还评估了它们的形态，而对于 HOBs，则观察了 ALP 和矿化。结果表明， 和 对细胞活力均无不良影响，在较低浓度 (5 µM) 下，与 RSV 相比，两者甚至显著提高了增殖率。形态观察指出，5 µM 的 和 促进了 HUVECs 和 HGFs 的密度，促进了 HOBs 的矿化。此外，与 RSV 相比， 和 (5 µM) 在 HUVECs 中诱导更高的 eNOS mRNA 水平，在 HGFs 中诱导更高的 COL1 mRNA 水平，在 HOBs 中诱导更高的 OCN 水平。 和 具有可观的物理化学性质、良好的酶和化学稳定性以及有前途的生物学特性，为进一步研究提供了科学依据，以开发在口腔组织修复中有用的基于 RSV 的制剂。
