3--hydroxypterostilbene and 3-3--4-5--tetrahydroxystilbene

Inflammatory bowel disease has become a significant health concern across the globe, causing frequent and long-term harm to the digestive system. This study evaluated the effect of piceatannol (PIC) and 3'-hydroxypterostilbene (HPSB) on dextran sulfate sodium (DSS)-induced colitis in mice and investigated whether their effects are exerted through the amelioration of gut barrier dysfunction to reduce the severity of colitis. The findings showed that both PIC and HPSB attenuated inflammation by inhibiting the TNF-α/NF-κB/MLC pathway and reducing NLRP3 inflammasome activation. However, PIC was comparably effective in modulating tight junctions. The results may be attributed to the effect of PIC on reducing cell apoptosis-associated protein expression, including Bax/Bcl-2 and caspase-3 activation. Furthermore, microbiota analysis revealed that both PIC and HPSB increased representative probiotic species, including

Topics: Animals; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Inflammation; Inflammatory Bowel Diseases; Mice; Mice, Inbred C57BL

Stilbenes with well-known antioxidant and antiradical properties are beneficial in different pathologies including cardiovascular diseases. The present research was performed to investigate the potential protective effect of resveratrol (1) and piceatannol (2), against hypoxia-induced oxidative stress in the H9c2 cardiomyoblast cell line, and the underlying mechanisms. Compounds 1 and 2 significantly inhibited the release of peroxynitrite and thiobarbituric acid levels at na no- or submicromolar concentrations, and this effect was more evident in piceatannol-treated cells, that significantly increased MnSOD protein level in a concentration dependent manner. Furthermore, since piceatannol, which is far less abundant in natural sources, displayed a higher bioactivity than the parent compound, we hereby report on a very fast synthesis and detailed structure-based design of a focused stilbene library. Finally, taking into account that hypoxia-induced ROS accumulation also increases expression and activity of 5-lipoxygenase (5-LOX) with production of leukotrienes, we have disclosed structural key factors crucial for 5-LOX activity. Among the synthesized analogues ( 3-7), compound 7 was the most effective in improving cardiomyocytes viability and in 5-LOX inhibition. In conclusion, modeling and experimental studies provided the basis for further optimization of stilbene analogues as multi-target inhibitors of the inflammatory and oxidative pathway.

Topics: Animals; Arachidonate 5-Lipoxygenase; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Hypoxia; Lipoxygenase Inhibitors; Molecular Structure; Myocytes, Cardiac; Protective Agents; Rats; Stilbenes; Structure-Activity Relationship