Current pharmacological developments in 2,3,4',5-tetrahydroxystilbene 2-O-ß-D-glucoside (TSG).

2,3,4',5-tetrahydroxystilbene 2-O-ß-D-glucoside (TSG), a resveratrol analog with glucoside, is purified from a traditional Chinese herbal medicine polygonum multiflorum. It has been extensively studied in last decade and known to exert strong anti-inflammatory, anti-oxidative, anti-apoptotic, and free radical scavenging activities, and therefore has been listed as a potential agent for disease therapies. Recent studies extend well-beyond effects of TSG on the injury of neurons, cardiomyocytes and endothelial cells, and report important functions of TSG in a lot of pathophysiological conditions. For example, TSG has been shown to prevent the production of pro-inflammatory cytokines in microglia and macrophages in vitro, and ameliorate pro-inflammatory responses in animal models with neurodegeneration, atherosclerosis, and rat paw or ear oedema. TSG can prevent the proliferation of vascular smooth cells, gastrointestinal dysfunctions, platelet aggregation, osteoblastic injury, diabetic nephropathy and melanogenesis. TSG is also indicated to facilitate long-term potentiation and learning and memory in both normal and pathological conditions. These effects to some extent enrich the understanding about the role of TSG in disease prevention and therapy. However, to date, we still have no outlined knowledges about the pharmacological effects of TSG, though the role of TSG in aging and Alzheimer's disease has been reviewed in recent years. Here, we summarize the current pharmacological developments of TSG as well as its possible mechanisms in disease prevention and therapy, aiming to push the understanding about the protective role of TSG as well as its preclinical assessment of novel applications.

Tetrahydroxystilbene glucoside improves TNF-α-induced endothelial dysfunction: involvement of TGFß/Smad pathway and inhibition of vimentin expression.

Endothelial dysfunction plays an important role in the pathogenesis of atherogenesis. 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG), an active component of the rhizome extract from Polygonum multiflorum (PM), exhibits significant anti-atherosclerotic activity. Here, we used human umbilical vein endothelial cells (HUVECs) induced by tumor necrosis factor-α (TNF-α) in vitro to investigate the cytoprotective effects of TSG on TNF-α-induced endothelial injury and the related mechanisms. Pretreatment with 50 and 100 µM TSG markedly attenuated TNF-α-induced loss of cell viability and release of lactate dehydrogenase (LDH) and inhibited TNF-α-induced cell apoptosis. The inhibition of vimentin expression was involved in the cytoprotection afforded by TSG. Using inhibitors for PI3K and TGFß or siRNA for Akt and Smad2, we found that vimentin production in HUVECs is regulated by TGFß/Smad signaling, but not by PI3K-Akt-mTOR signaling. Meanwhile, TSG inhibited both the expression of TGFß1 and the phosphorylation of Smad2 and Smad3, and TSG suppressed the nuclear translocation of Smad4 induced by TNF-α. These results suggest that TSG protects HUVECs against TNF-α-induced cell damage by inhibiting vimentin expression via the interruption of the TGFß/Smad signaling pathway.

Proteomic analysis for anti-atherosclerotic effect of tetrahydroxystilbene glucoside in rats.

2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) extracted from Polygonum multiflorum (a traditional Chinese medicinal herb) has been proved to exhibit significant anti-atherosclerotic activity. In this study, we firstly used proteomic analyses to investigate the molecular events occurring in the atherosclerotic rats after TSG treatment. Aortic samples were collected from the atherosclerotic rat group and the TSG-treated group, and its proteome was analyzed by two-dimensional gel electrophoresis (2-DE). Proteins showing significant changes in expression were identified and analyzed by matrix-assisted desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). As a result, 21 protein spots were found with significant differential expression after the treatment with TSG. A total of 18 spots were identified by database searching, and 17 spots matched with known proteins. Among these proteins (11 proteins up-regulated and six proteins down-regulated), five proteins were mainly involved in inflammation, cholesterol transport, cell apoptosis and adhesion. TSG treatment enhanced the expression of HSP 70, lipocortin 1 and Apo A-I, and inhibited the expression of calreticulin, vimentin. Furthermore, we randomly selected four proteins and confirmed the results of proteomic analysis by RT-PCR and western blotting. In conclusion, TSG treatment suppresses atherosclerosis by altering the expression of different proteins. Calreticulin, vimentin, HSP 70, lipocortin 1, and Apo A-I, are key proteins that may be novel molecular targets responsible for atherogenesis suppression induced by TSG treatment.