tetrahydroxystilbene-2-O-beta-D-glucoside Research Articles

2, 3, 5, 4'-tetrahydroxystilbene-2-O-beta-D-glucoside protects against neuronal cell death and traumatic brain injury-induced pathophysiology.

Traumatic brain injury (TBI) is a global health issue that affects at least 10 million people per year. Neuronal cell death and brain injury after TBI, including apoptosis, inflammation, and excitotoxicity, have led to detrimental effects in TBI. 2, 3, 5, 4’-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), a water-soluble compound extracted from the Chinese herb Polygonum multiflorum, has been shown to exert various biological functions. However, the effects of THSG on TBI is still poorly understood. THSG reduced L-glutamate-induced DNA fragmentation and protected glial and neuronal cell death after L-glutamate stimulation. Our results also showed that TBI caused significant behavioral deficits in the performance of beam walking, mNSS, and Morris water maze tasks in a mouse model. Importantly, daily administration of THSG (60 mg/kg/day) after TBI for 21 days attenuated the injury severity score, promoted motor coordination, and improved cognitive performance post-TBI. Moreover, administration of THSG also dramatically decreased the brain lesion volume. THSG reduced TBI-induced neuronal apoptosis in the brain cortex 24 h after TBI. Furthermore, THSG increased the number of immature neurons in the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus. Our results demonstrate that THSG exerts neuroprotective effects on glutamate-induced excitotoxicity and glial and neuronal cell death. The present study also demonstrated that THSG effectively protects against TBI-associated motor and cognitive impairment, at least in part, by inhibiting TBI-induced apoptosis and promoting neurogenesis.

Reduction of breast tumor drug resistance by 2,3,5,4'-tetrahydroxystilbene for exhibition synergic chemotherapeutic effect.

Chemotherapy drugs have limited efficacy in breast cancer due to multidrug resistance generated by cancer cells against anticancer drugs. In this study, we developed a novel derivative, 2, 3, 5, 4‘-tetrahydroxystilbene (TG1) by modifying 2, 3, 5, 4‘-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG). In-vivo zebrafish embryo tests revealed that TG1 showed low toxicity. The equitoxic combination of DOX or DTX with TG1 in MCF-7/Adr reduced the IC50 of DOX or DTX, and the combination index (CI) showed strong synergistic effects in the 1:3 molar ratio of DTX: TG1 and 1:5 molar ratio of DOX: TG1. Moreover, fluorescence images confirmed the cellular uptake of DOX when combined with TG1 in MCF-7/Adr. Western blotting analysis indicated downregulation of p-glycoprotein (P-gp) after MCF-7/Adr treated with TG1. In conclusion, the combined therapy of DTX or DOX and TG1 increases drug efficacy via suppressing the p-glycoprotein efflux pump. These results suggest that TG1 may have potential use for breast cancer patients, especially those with multidrug resistance.

Hepatoprotection and hepatotoxicity of Heshouwu, a Chinese medicinal herb: Context of the paradoxical effect

Heshouwu (Polygonum multiflorum Thunb.) has been a common Chinese medicine and a folk Taoist medicine for over a thousand years. There are two drug forms, Shengshouwu (Polygoni Multiflori Radix) and Zhiheshouwu (Polygoni Multiflori Radix Prapaerata) in the Chinese Pharmacopoeia. In this review, we retrieved articles with such keywords as Heshouwu, liver protection and liver toxicity in the databases of PubMed and the China National Knowledge Infrastructure (CNKI). Hepatoprotection and hepatotoxicity of Shengshouwu and Zhiheshouwu in vitro and in vivo, and their clinical settings and adverse drug reactions (ADR) were summarized, analyzed and critically reviewed. In bench research, both drug forms had effects against nonalcoholic fatty liver disease, oxidation, fibrosis, cirrhosis, and liver cancer. Clinically, Heshouwu was used for treating fatty liver disease (FLD), hyperlipidemia, cirrhosis and hepatitis B. In contrast, both drug forms could lead to drug-induced liver injury and even death in vitro, in vivo and in clinical settings. In addition, the active components of both drug forms had hepatic benefits and toxicity in interaction with emodin, physcion, and probably 2,3,5,4′-tetrahydroxy-stilbene-2-O-beta-d-glucoside (TSG). In conclusion, Heshouwu exhibited both hepatoprotection and hepatotoxicity. It is essential to evaluate the advantages and disadvantages when Heshouwu is in clinical use.

Effective Energy Transfer via Plasmon-Activated High-Energy Water Promotes Its Fundamental Activities of Solubility, Ionic Conductivity, and Extraction at Room Temperature.

Water is a ubiquitous solvent in biological, physical, and chemical processes. Unique properties of water result from water’s tetrahedral hydrogen-bonded (HB) network (THBN). The original THBN is destroyed when water is confined in a nanosized environment or localized at interfaces, resulting in corresponding changes in HB-dependent properties. In this work, we present an innovative idea to validate the reserve energy of high-energy water and applications of high-energy water to promote water’s fundamental activities of solubility, ionic conductivity, and extraction at room temperature. High-energy water with reduced HBs was created by utilizing hot electrons with energies from the decay of surface plasmon excited at gold (Au) nanoparticles (NPs). Compared to conventional deionized (DI) water, solubilities of alkali metal-chloride salts in high-energy water were significantly increased, especially for salts that release heat when dissolved. The ionic conductivity of NaCl in high-energy water was also markedly higher, especially when the electrolyte’s concentration was extremely low. In addition, antioxidative components, such as polyphenols and 2,3,5,4’-tetrahydroxystilbene-2-O-beta-d-glucoside (THSG) from teas, and Polygonum multiflorum (PM), could more effectively be extracted using high-energy water. These results demonstrate that high-energy water has emerged as a promising innovative solvent for promoting water’s fundamental activities via effective energy transfer.

2, 3, 5, 4'-Tetrahydroxystilbene-2-O-beta-D-glucoside improves gastrointestinal motility disorders in STZ-induced diabetic mice.

Oxidative stress has recently been considered as a pivotal player in the pathogenesis of diabetic gastrointestinal dysfunction. We therefore investigated the role of 2, 3, 5, 4′-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG) that has a strong anti-oxidant property, in diabetic gastrointestinal dysmotility as well as the underlying protective mechanisms. THSG restored the delayed gastric emptying and the increased intestinal transit in streptozotocin (STZ)-induced diabetic mice. Loss of neuronal nitric oxide synthase (nNOS) expression and impaired nonadrenergic, noncholinergic (NANC) relaxations in diabetic mice were relieved by long-term preventive treatment with THSG. Meanwhile, THSG (10−7∼10−4 mol/L) enhanced concentration-dependently NANC relaxations of isolated colons in diabetic mice. Diabetic mice displayed a significant increase in Malondialdehyde (MDA) level and decrease in the activity of glutathione peroxidase (GSH-Px), which were ameliorated by THSG. Inhibition of caspase-3 and activation of ERK phosphorylation related MAPK pathway were involved in prevention of enhanced apoptosis in diabetes afforded by THSG. Moreover, THSG prevented the significant decrease in PPAR-γ and SIRT1 expression in diabetic ileum. Our study indicates that THSG improves diabetic gastrointestinal disorders through activation of MAPK pathway and upregulation of PPAR-γ and SIRT1.

Beneficial Effects of THSG on Acetic Acid-Induced Experimental Colitis: Involvement of Upregulation of PPAR-γ and Inhibition of the Nf-Κb Inflammatory Pathway

The polyphenolic compound 2,3,5,4′-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG) has been shown to possess anti-inflammatory effects. Here, we examined the effects of THSG on experimental mice with colitis induced by acetic acid and whether the underlying mechanisms were associated with the PPAR-γ and NF-κB pathways. Mice were randomized into six equal groups: normal, colitis model, THSG (10, 30, 60 mg·kg−1) and mesalazine. The mice were administered 10, 30, 60 mg·kg−1 THSG or 100 mg·kg−1 mesalazine or saline once daily by intragastric administration for 7 days after induction of colitis by acetic acid irrigation. THSG dramatically attenuated acetic acid-induced colon lesions, including reversing the body weight loss and improving histopathological changes. THSG apparently decreased the increase of malondialdehyde (MDA) which is a marker of lipid peroxidation. THSG appears to exert its beneficial effects on acetic acid-induced experimental colitis through upregulation of PPAR-γ mRNA and protein levels and inhibition of the NF-κB pathway, which in turn decreases the protein overexpression of the downstream inflammatory mediators TNF-α, IL-6 and COX-2. The effect of THSG 60 mg·kg−1 on PPAR-γ mRNA expression was higher than that of mesalazine. THSG may thus be a promising new candidate or lead compound for the treatment of IBD.

Stilbene Glucoside from Polygonum multiflorum Thunb.: A Novel Natural Inhibitor of Advanced Glycation End Product Formation by Trapping of Methylglyoxal

Methylglyoxal (MGO), the reactive dicarbonyl intermediate generated during the nonenzymatic glycation between reducing sugars and amino groups of proteins, lipids, and DNA, is the precursor of advanced glycation end products (AGEs). Many studies have shown that AGEs play a major pathogenic role in diabetes and its complications. This study found that 2,3,5,4'-tetrahydroxystilbene 2-O-beta-D-glucoside (THSG), the major bioactive compound from Polygonum multiflorum Thunb., can efficiently inhibit the formation of AGEs in a dose-dependent manner by trapping reactive MGO under physiological conditions (pH 7.4, 37 degrees C). More than 60% MGO was trapped by THSG within 24 h, which was much more effective than resveratrol and its methylated derivative, pterostilbene, the two major bioactive dietary stilbenes. The major mono- and di-MGO adducts of THSG were successfully purified and found to be mixtures of tautomers. LC-MS and NMR data showed that positions 4 and 6 of the A ring were the major active sites for trapping MGO. It was also found that THSG could significantly inhibit the formation of AGEs in the human serum albumin (HSA)-MGO assay and both mono- and di-MGO adducts of THSG were detected in this assay using LC-MS. The results suggest that the ability of THSG to trap reactive dicarbonyl species makes it a potential natural inhibitor of AGEs.

Protective effect of tetrahydroxystilbene glucoside on cardiotoxicity induced by doxorubicin in vitro and in vivo

To test the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG) on doxorubicin (DOX)-induced cardiotoxicity. We used neonate rat cardiomyocytes and an acute mouse model of DOX-induced cardiotoxicity to examine the protective effect of THSG. In the mouse model, administration of THSG significantly reduced DOX-induced cardiotoxicity, including animal mortality, histopathological changes, and levels of serum creatine kinase (CK) and lactate dehydrogenase (LDH). Moreover, THSG was able to attenuate the increased malondialdehyde (MDA) and decreased reduced glutathione (GSH) caused by DOX. In in vitro studies, THSG 10-300 micromol/L ameliorated DOX-induced cardiomyocyte apoptosis in a concentration-dependent manner. Further studies showed that THSG inhibited reactive oxygen species (ROS) generation and prevented DOX-induced loss of mitochondrial membrane potential, caspase-3 activation and upregulation of Bax protein expression. We observed a protective response against damage after DOX treatment. The level of Bcl-2 protein was increased. Additionally, THSG inhibited a DOX-induced [Ca(2+)] increase. These results showed that THSG protected against DOX-induced cardiotoxicity by decreasing ROS generation and intracellular [Ca(2+)] and by inhibiting apoptotic signaling pathways.

Effect of 2,3,5,4′-tetrahydroxystilbene-2-O-beta-d-glucoside on lipoprotein oxidation and proliferation of coronary arterial smooth cells

To investigate the effects of 2,3,5,4′-tetrahydroxystilbene-2-O-beta-d-glucoside (THSG), a compound extracted from the root of Polygonum multiflorum Thunb, on lipoprotein (LDL and VLDL) oxidation, proliferation and nitric oxide (NO) content of coronary arterial smooth cells (CASMCs) induced by LDL, VLDL, ox-LDL and ox-VLDL. The oxidation level of lipoprotein was determined by thiobabituric acid (TBA) method and agarose gel electrophoresis. The proliferative degree was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) method. The NO content was assayed by nitrate reductase method. (1)THSG (0.1 ∼ 100 μmol·L− 1) could dose-dependently prevent lipoprotein from oxidation induced by Cu2+ and CASMCs. (2)THSG (0.1 ∼ 100 μmol·L− 1) inhibited porcine CASMCs proliferation elicited by LDL, VLDL, ox-LDL and ox-VLDL. (3)THSG (0.1 ∼ 100 μmol·L− 1) counterpoised the decrease of NO content in CASMCs evoked by LDL, VLDL, ox-LDL and ox-VLDL. As compared with control, it was found that the threshold concentration of THSG, which significantly exerted the actions mentioned above, were at the concentration of 1μmol·L− 1 (P < 0.01). In conclusion, THSG possesses the antagonistic effects on oxidation of lipoprotein, proliferation and decrease of NO content of CASMCs, which partially explain the mechanism of anti-atherosclerosis of Polygonum multiflorum Thunb.

Protective effects of 2,3,5,4′-tetrahydroxystilbene-2- O-beta- d-glucoside, an active component of Polygonum multiflorum Thunb, on experimental colitis in mice

Reactive oxygen metabolites (ROMs) and inducible nitric oxide synthase (iNOS) are involved in pathogenesis of inflammatory bowel disease. In this study, we examined the effects of 2,3,5,4′-tetrahydroxystilbene-2- O-beta- d-glucoside (THSG), an active component extracted from Polygonum multiflorum Thunb, on acetic acid-induced acute colitis and mitomycin C-induced chronic colitis. The inflammatory degree was assessed by histology and myeloperoxidase (MPO) activity. Nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined with biochemical methods. In addition, inducible nitric oxide synthase (iNOS) expression was innumohistochemically studied. In acetic acid-induced acute model, THSG (60 and 120 mg/kg) significantly ameliorated colon damage, inhibited the increase of acetic acid-induced MPO activity, depressed MDA and NO level, and enhanced SOD activity. Moreover, the effects of 120 mg/kg THSG were better than that of positive control drug, 5-aminosaliylic acid (5-ASA). In mitomycin C-induced model, THSG (60 mg/kg) administered for 7 days and 24 days, significantly improved colon damage and inhibited MPO activity and MDA content while increased SOD activity only on the 7th day and debased NO level on the 24th day. Furthermore, on the 24th day, the effects of THSG were prior to that of 5-ASA. Additionally, THSG (60 mg/kg) could inhibit iNOS expression in both models. In conclusion, THSG exerts protective effects on experimental colitis through alleviating oxygen and nitrogen free radicals level and down-regulating iNOS expression.