Inhibitory Effects of Pinostilbene on Adipogenesis in 3T3-L1 Adipocytes: A Study of Possible Mechanisms

Resveratrol is a phytoalexin with multiple bioactive properties, including antioxidative, neuroprotective, cardioprotective, and anticancer effects. However, resveratrol exhibits structural instability in response to UV irradiation, alkaline pH, and oxygen exposure. Thus, resveratrol derivatives have attracted considerable research interest. In this study, we aimed to evaluate the anti-adipogenic effects of pinostilbene hydrate (PH), a methylated resveratrol derivative, in 3T3-L1 cells. We also evaluated the mechanisms underlying the effects of PH on adipogenesis in 3T3-L1 adipocytes. Oil Red O staining, lipid accumulation assay, and triglyceride (TG) content assay revealed that PH significantly inhibited lipid and TG accumulation without cytotoxicity. In addition, we determined that PH decreased the expression of adipogenesis-related transcription factors, such as PPARγ, C/EBPα, SREBP-1c, and FABP4, and the phosphorylation of MAPK and protein kinase B (AKT). Moreover, PH attenuated the expression of CREB and C/EBPβ, while increasing the phosphorylation of AMPK and ACC, and decreasing the expression of fatty acid synthase and FABP4. Based on these results, we suggest that PH suppresses adipogenesis in 3T3-L1 cells via the activation of the AMPK signaling pathway and the inhibition of the MAPK and AKT insulin-dependent signaling pathways.

Design and identification of two novel resveratrol derivatives as potential LSD1 inhibitors

Background: Overexpression of LSD1 is associated with the occurrence of many diseases, including cancers, which makes LSD1 a significant target for anticancer drug research. Methodology & Results: With the aid of 3D quantitative structure–activity relationship models established with 34 reported resveratrol derivative LSD1 inhibitors, derivatives 35–40 were designed. Absorption, distribution, metabolism and excretion calculations showed that they may have good bioavailability and drug likeness. Additionally, 35 and 37 presented good antitumor effects in an in vitro antiproliferative assay. Molecular docking and molecular dynamics simulation results indicated that 35 and 37 can establish extensive interactions with LSD1. Conclusion: The results of computational prediction and experimental validation suggest that 35 and 37 are effective antitumor inhibitors, which provides some ideas and directions for the development of new anticancer LSD1 inhibitors.

Resveratrol Derivative, Trans-3, 5, 4 ′ -Trimethoxystilbene Sensitizes Osteosarcoma Cells to Apoptosis via ROS-Induced Caspases Activation

Numerous studies have shown that resveratrol can induce apoptosis in cancer cells. Trans-3, 5, 4 ′ -trimethoxystilbene (TMS), a novel derivative of resveratrol, is a more potent anticancer compound than resveratrol and can induce apoptosis in cancer cells. Herein, we examined the mechanisms involved in TMS-mediated sensitization of human osteosarcoma (143B) cells to TNF-related apoptosis-inducing ligand- (TRAIL-) induced apoptosis. Our results showed that cotreatment with TSM and TRAIL activated caspases and increased PARP-1 cleavage in 143B cells. Decreasing cellular ROS levels using NAC reversed TSM- and TRAIL-induced apoptosis in 143B cells. NAC abolished the upregulated expression of PUMA and p53 induced by treatment with TRAIL and TSM. Silencing the expression of p53 or PUMA using RNA interference attenuated TSM-mediated sensitization of 143B cells to TRAIL-induced apoptosis. Knockdown of Bax also reversed TSM-induced sensitization of 143B cell to TRAIL-mediated apoptotic cell death. These results indicate that cotreatment with TRAIL and TSM evaluated intracellular ROS level, promoted DNA damage, and activated the Bax/PUMA/p53 pathway, leading to activation of both mitochondrial and caspase-mediated apoptosis in 143B cells. Orthotopic implantation of 143B cells in mice also demonstrated that cotreatment with TRAIL and TSM reversed resistance to apoptosis in cells without obvious adverse effects in normal cells.

Piceid Nanoparticles Stabilized by Anionic Phospholipids for Transdermal Delivery

Piceid, stilbenoid glucoside, is a representative resveratrol derivative. Because of a high tyrosinase inhibitory activity of piceid through resveratrol derivatives, transdermal delivery of piceid has been desired for taking advantage of the activity. Here we successfully prepared composite nanoparticles composed of anionic phospholipid of 1,2-dipalmitoyl- sn-glycero-3-phosphorylglycerol (DPPG) and piceid by mixing them in water and a subsequent heating/cooling process. When small-sized fluorescently labeled DPPG-piceid (DPPG-FLpiceid) nanoparticles were added to rat skin tissue, FLpiceid molecules were localized in stratum corneum.