2-3-5-4--tetrahydroxystilbene-2-o-glucopyranoside and Disease-Models--Animal

2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG) is active component of the Chinese medicinal plant Polygonum multiflorum Thunb. (THSG). Pharmacological studies have demonstrated that THSG exhibits numerous biological functions in treating atherosclerosis, lipid metabolism, vascular and cardiac remodeling, vascular fibrosis, cardiac-cerebral ischemia, learning and memory disorders, neuroinflammation, Alzheimer and Parkinson diseases, diabetic complications, hair growth problems, and numerous other conditions. This review focuses on the biological effects of THSG in antiaging and antiaging-related disease treatments and discusses its molecular mechanisms.

Topics: Aging; Animals; Cardiovascular Agents; Cellular Senescence; Disease Models, Animal; Drugs, Chinese Herbal; Fallopia multiflora; Gene Expression Regulation; Glucosides; Humans; Hypoglycemic Agents; Neuroprotective Agents; Phytotherapy; Plants, Medicinal; Signal Transduction; Stilbenes

2,3,5,4'-Tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) is the main active component of Polygoni Multiflori Radix, a root of the homonymous plant widely used in traditional Chinese medicine. TSG has protective effects on the liver, reduces cholesterol and possesses anti-oxidant, anti-tumor, and anti-atherosclerotic properties. However, the pharmacological effects and mechanisms of action of Polygonum multiflorum on atherosclerosis (AS) have not been studied yet.. The aim of this research was to study the effects of Polygoni Multiflori Radix Praeparata (PMRP) and its major active chemical constituent TSG on AS in ApoE-deficient (ApoE. High fat diet induced AS in ApoE. TSG markedly inhibited AS plaque formation in ApoE. PMRP and TSG improved lipid accumulation and inflammation, and regulated the intestinal microbial imbalance in ApoE

Topics: Administration, Oral; Animals; Aorta; Atherosclerosis; Chemokine CCL2; Diet, High-Fat; Disease Models, Animal; Drugs, Chinese Herbal; Gastrointestinal Microbiome; Glucosides; Humans; Inflammation; Intercellular Adhesion Molecule-1; Lipoproteins, LDL; Male; Mice; Mice, Knockout, ApoE; Polygonum; Stilbenes; Triglycerides; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

With the improvement of people's living standards and the change of dietary habits, Non-alcoholic fatty liver disease (NAFLD) has gradually become one of the liver diseases that endanger human health around the world. However, there are no particularly effective drugs for NAFLD in the current market. Therefore, new drug candidates which could provide high efficacy and low toxicity are needed valuable for the prevention and treatment of NAFLD. 2,3,5,4'-tetrahydroxystilbence-2-O-β-D-glucoside (TSG) is extracted from Polygonum multiflorum Thunb., and has been widely used to treat a variety of chronic diseases in China. Recently, TSG has been reported to exert various biological activities in many studies, such as lipid-lowering, anti-inflammatory and anti-oxidant activities, which indicate that TSG may have the effect of improving NAFLD. After feeding 5% high cholesterol diet to 5 days post fertilization larval zebrafish for 10 days, hepatic steatosis larval zebrafish model was established successfully. Then the effect of TSG on the improvement of hepatic steatosis larval zebrafish was studied. Moreover, the potential mechanism of TSG on anti-NAFLD effect were studied using RT-qPCR methods from multiple pathogenesis aspects of lipogenesis, lipid-lowering, inflammation, and oxidant stress. To conclude, TSG attenuates hepatic steatosis via regulating lipid metabolism related pathway, IKKβ/NF-κB anti-inflammatory pathway and Keap1-Nrf2 anti-oxidant pathway.

Topics: Animals; Cholesterol, Dietary; Disease Models, Animal; Glucosides; I-kappa B Kinase; Kelch-Like ECH-Associated Protein 1; Lipid Metabolism; NF-E2-Related Factor 2; NF-kappa B; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Signal Transduction; Stilbenes; Zebrafish; Zebrafish Proteins

Although the therapeutic potential of human dental pulp stem cells (hDPSCs) has been studied for bone regeneration, the therapeutic efficiency needs further consideration and examinations for clinical applications. Thus, the aims of this study were to evaluate the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) on the osteogenic differentiation of hDPSCs and to examine the therapeutic efficiency of the THSG-enhanced osseous potential of hDPSCs in alveolar bony defects of rats.. Expressions of osteogenic messenger RNAs (including ALP, RUNX2, BGLAP, and AMBN) were examined by quantitative real-time polymerase chain reaction. Alizarin red S staining was conducted to analyze THSG-induced mineralization of hDPSCs. To investigate the regenerative effects of THSG-treated hDPSCs on dental alveolar bone, bony defects were created in male Sprague-Dawley rats. Defects were treated with Matrigel (Corning Inc, Corning, NY), hDPSCs, or hDPSCs + THSG. After 2 weeks, defect healing was evaluated by micro-computed tomographic and histologic analyses.. In the cell model, THSG induced osteogenesis-associated genes (ALP, RUNX2, and BGLAP) and an enamel-related gene (AMBN), resulting in mineralization as detected by alizarin red S staining after 2 weeks of treatment. In the animal model, THSG increased all parameters of bone formation (the relative bone volume, trabecular thickness, trabecular number, and trabecular separation) in alveolar bony defects of rats. THSG not only improved the quality of newly formed bone but also the quantity of new bone.. These results showed important findings in revealing the THSG-enhanced osteogenic differentiation of hDPSCs and THSG-facilitated bone regeneration, which may provide an alternative option for cell-based regenerative therapy.

Topics: Adolescent; Adult; Alveolar Bone Loss; Alveolar Process; Animals; Bone Regeneration; Cell Differentiation; Dental Pulp; Disease Models, Animal; Female; Glucosides; Humans; Male; Osteogenesis; Rats, Sprague-Dawley; Regenerative Medicine; Stem Cell Transplantation; Stem Cells; Stilbenes; Stimulation, Chemical; Young Adult

Topics: Animals; Biomarkers; Body Weight; Bone and Bones; Disease Models, Animal; Glucosides; Humans; Mice; Organ Size; Osteoporosis; Ovariectomy; Plant Extracts; Protective Agents; Stilbenes; X-Ray Microtomography

Asthma is an inflammatory disease caused by an imbalance of Th1 and Th2 cells. In general, asthma is characterized by a stronger Th2 response. Most conventional asthma treatment focuses on improving airway flow or suppression of airway inflammation. To reduce the side effects of currently used asthma medicines, we have conducted studies on natural products that have no side effects. 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside (TSG), the main compound of

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Cell Count; Cytokines; Disease Models, Animal; Female; Glucosides; Immunoglobulin Class Switching; Inflammation; Inflammation Mediators; Lung; Mice, Inbred C57BL; Ovalbumin; Protective Agents; Respiratory Hypersensitivity; Stilbenes; Th1 Cells; Th2 Cells

Cardiac stem cells (CSCs)-transplanted therapy provides a promising therapy for the ischemic heart disease (IHD), especially in the epidemic of myocardial infarction (MI). The compound 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside (THSG) can induce CSC proliferation in vitro based on our previous study, so we aimed to study the induce effect of THSG on CSCs-transplanted MI rat in vivo.. Using a murine model of MI, this study was designed to evaluate the impact of THSG (30, 60, 120mg/kg) on CSCs-based therapy for MI and the underlying mechanism in this process.. The results showed that THSG on CSCs-transplanted therapy groups (THSG+CSCs groups) can significantly reduce S-T segment elevation, and increase heart rate compared with MI group. The left ventricular ejection fraction (LVEF) and the left ventricular fractional shortening (LVFS) were significantly reduced in THSG+CSCs groups compared to the MI group. The levels of enzyme expression (CK-MB, LDH), the heart weight index (HWI) and myocardial infarct size (IS) were all reduced in THSG+CSCs groups. Moreover, other changes noted during these 28days post-MI, included pathologic changes, as well as increased stem cell antigen-1 (Sca-1) expression, or expression of Nkx2.5, GATA-4, and Connexin 43 in myocardial tissue, and reduced the Caspase-3 expression.. Our findings indicated that THSG facilitated CSCs-transplanted therapy in MI. These observations may be associated with the inducted of THSG on the proliferation of CSCs in vivo and also, with the subsequent differentiation of additional intrinsic neonatal cardiomyocytes to replace damaged heart tissue.

Topics: Animals; Disease Models, Animal; Glucosides; Heart Rate; Male; Myocardial Infarction; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley; Stem Cell Transplantation; Stilbenes

Memory impairment can be progressive in neurodegenerative diseases, and physiological ageing or brain injury, mitochondrial dysfunction and oxidative stress are critical components of these issues. An early clinical study has demonstrated cognitive improvement during erythropoietin treatment in patients with chronic renal failure. As erythropoietin cannot freely cross the blood-brain barrier, we tested EH-201 (2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside, also known as TSG), a low MW inducer of erythropoietin, for its therapeutic effects on memory impairment in models of neurodegenerative diseases, physiological ageing or brain injury.. The effects of EH-201 were investigated in astrocytes and PC12 neuronal-like cells. In vivo, we used sleep-deprived (SD) mice as a stress model, amyloid-β (Aβ)-injected mice as a physiological ageing model and kainic acid (KA)-injected mice as a brain damage model to assess the therapeutic effects of EH-201.. EH-201 induced expression of erythropoietin, PPAR-γ coactivator 1α (PGC-1α) and haemoglobin in astrocytes and PC12 neuronal-like cells. In vivo, EH-201 treatment restored memory impairment, as assessed by the passive avoidance test, in SD, Aβ and KA mouse models. In the hippocampus of mice given EH-201 in their diet, levels of erythropoietin, PGC-1α and haemoglobin were increased. The induction of endogenous erythropoietin in neuronal cells by inducers such as EH-201 might be a therapeutic strategy for memory impairment in neurodegenerative disease, physiological ageing or traumatic brain injury.

Topics: Animals; Astrocytes; Cells, Cultured; Disease Models, Animal; Erythropoietin; Female; Glucosides; Hemoglobins; Hydrogen Peroxide; Kainic Acid; Male; Memory Disorders; Mice, Inbred C57BL; Mitochondria; Neuroprotective Agents; PC12 Cells; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Rats; Reactive Oxygen Species; Stilbenes; Succinate Dehydrogenase; Transcription Factors

Parkinson's disease (PD) is characterized by the selective death of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress-induced neuron loss is thought to play a crucial role in the pathogenesis of PD. Previous work from our group suggests that 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from a traditional Chinese herb, Polygonum multiflorum thunb, can attenuate 1-methyl-4-phenyl pyridium-induced apoptosis in the neuronal cell line PC12, by inhibiting reactive oxygen species generation and modulating c-Jun N-terminal kinases (JNK) activation. Here, we investigated the protective effects of TSG against 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP)-induced loss of tyrosine hydroxylase positive cells in mice and the underlying mechanisms. The results showed that MPTP-induced loss of tyrosine hydroxylase positive cells and reactive oxygen species generation were prevented by TSG in a dose-dependent manner. The reactive oxygen species scavenger N-acetylcysteine could also mitigate reactive oxygen species generation. Moreover, JNK and P38 were activated by MPTP, but extracellular signal-regulated protein kinases phosphorylation did not change after MPTP treatment. TSG at different doses blocked the activation of JNK and P38. The protective effect of TSG was also associated with downregulation of the bax/bcl-2 ratio, reversed the release of cytochrome c and smac, and inhibited the activation of caspase-3, -6, and -9 induced by MPTP. In conclusion, our studies demonstrated that the protective effects of TSG in the MPTP-induced mouse model of PD are involved, at least in part, in controlling reactive oxygen species-mediated JNK, P38, and mitochondrial pathways.

Topics: Animals; Apoptosis Regulatory Proteins; Behavior, Animal; Disease Models, Animal; Dopamine; Dopaminergic Neurons; Dose-Response Relationship, Drug; Extracellular Signal-Regulated MAP Kinases; Glucosides; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Signaling System; Mice; Mitochondria; Neuroprotective Agents; Parkinsonian Disorders; Phosphorylation; Reactive Oxygen Species; Stilbenes; Tyrosine 3-Monooxygenase

Our in vitro experiments suggested that tetrahydroxystilbene glucoside (TSG) affords a significant neuroprotective effect against MPP⁺-induced damage and apoptosis in PC12 cells though activation of the PI3K/Akt pathway. This study was aimed to investigate the potential neuroprotective effect of TSG in 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP)-treated mouse model of Parkinson's disease (PD). We found that treatment of TSG protected dopaminergic neurons by preventing MPTP-induced decreases in substantia nigra tyrosine hydroxylase (TH)-positive cells and striatal dopaminergic transporter (DAT) protein levels. Furthermore, it was also associated with increasing striatal Akt and GSK3β phosphorylation, up-regulation of the Bcl-2/BAD ratio, and inhibition of the activation of caspase-9 and caspase-3. These results showed that TSG promoted dopamine neuron survival in vivo, the PI3K/Akt signaling pathway may have mediated the protection of TSG against MPTP, suggesting that TSG treatment might represent a neuroprotective treatment for PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Apoptosis Regulatory Proteins; Ataxia; Behavior, Animal; Cell Survival; Corpus Striatum; Disease Models, Animal; Dopamine Plasma Membrane Transport Proteins; Dopaminergic Neurons; Glucosides; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Male; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Neuroprotective Agents; Parkinson Disease; Proto-Oncogene Proteins c-akt; Signal Transduction; Stilbenes; Substantia Nigra; Tyrosine 3-Monooxygenase

To investigate the effects of terahydroxy stilbene glucoside (TSG) on neurological deficits, the expressions of nerve growth factor (NGF) and growth associated protein43 (GAP43) in rats after Cerebral Ischemia-reperfusion.. 96 Sprague-Dawley male rats were divided into four groups (n = 24): control group, ischemia-reperfusion (I/R) model group, low dose TSG (60 mg/kg) group and high dose TSG (120 mg/kg) group. After 6 days' administration of TSG or natural saline (model group), reversible middle cerebral artery occlusion (MCAO) model was established by intraluminal suture technique. Rats in control group were operated while middle cerebral artery were not blocked. At 6, 24, 48 h and 7 d after reperfusion, behavior test was used to evaluate the neurological deficiency of each group. The expressions of NGF and GAP-43 in the cortex were measured by immunohistochemical method.. Compared with model group, both dose of TSG could decrease the grade of the rat neurological defects except at 6 h of ter reperfusion and increase the protein expressions of NGF and GAP-43 after reperfusion.. TSG can improve the neurological function through increasing the expressions of NGF and GAP-43 of cerebral ischemia-reperfusion rats.

Topics: Animals; Brain Ischemia; Cerebral Cortex; Disease Models, Animal; GAP-43 Protein; Glucosides; Immunohistochemistry; Infarction, Middle Cerebral Artery; Male; Nerve Growth Factor; Neuroprotective Agents; Polygonaceae; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Stilbenes

2,3,4',5-Tetrahydroxystilbene 2- O-beta- D-glucoside (TSG), an active component extracted from Polygonum multiflorum, has been found to have an anti-atherosclerotic effect. The aim of this study was to investigate whether the TSG could prevent the development of atherosclerosis through influencing endothelial function in atherogenic-diet rats and to explore the possible mechanisms. Vascular endothelial dysfunction was assessed using isolated aortic ring preparation, transmission electron microscopy of the aorta, and levels of nitrate/nitrite (NOx) in serum and aorta. Endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) mRNA and protein expression were also measured. After 12 weeks treatment, TSG improved acetylcholine-induced endothelium-dependent relaxation, prevented intimal remodeling, inhibited the decreased NOx content in serum and aorta in atherogenic-diet rats. Furthermore, the observed decreased eNOS mRNA and protein expression and increased iNOS mRNA and protein expression in atherogenic-diet rats were attenuated by TSG treatment. These results suggest that TSG could restore vascular endothelial function, which may be related to its ability to prevent changes of eNOS and iNOS expression, leading to preservation of NO bioactivity.

Topics: Animals; Aorta; Atherosclerosis; Disease Models, Animal; Drugs, Chinese Herbal; Endothelium, Vascular; Glucosides; Male; Microscopy, Electron, Transmission; Nitrates; Nitric Oxide Synthase; Nitrites; Polygonum; Rats; Rats, Sprague-Dawley; RNA, Messenger; Stilbenes

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.

Topics: Animals; Animals, Newborn; Antibiotics, Antineoplastic; Apoptosis; Calcium; Cardiotonic Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Doxorubicin; Glucosides; Heart Diseases; Male; Mice; Myocytes, Cardiac; Rats; Reactive Oxygen Species; Signal Transduction; Stilbenes

To investigate learning-memory deficit in different ages of AD-like APP transgenic mice and to observe the protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), which is the main component of Polygonum multiflorum, on learning-memory abilities.. PDAPPV717I transgenic (Tg) mice were randomly divided into 3 model groups (4, 10 and 16 months old mice) and TSG treated (at doses 120 and 240 micromol/kg/d) groups. TSG was administered to some Tg mice with an age range 4-10 months. In untreated 10 months old Tg mice, the TSG was administrated to those falling in the age range 10-16 months. For the control group we adopted the same age and background C57BL/6J mice. The learning-memory ability was measured by applying Morris water maze (MWM) and object recognition test (ORT).. In the 4 months old PDAPPV717I Tg mice, the learning-memory deficit was detected. The escape latency in MWM was prolonged, and the discrimination index decreased in ORT. In the 10 months old Tg mice, the learning-memory deficit was aggravated. TSG improved all spatial learning-memory impairment in MWM as well as the object recognition impairment in ORT. In the 16 months old Tg mice, the learning-memory deficit remained to exist but abated a lot. TSG showed significant improvement in learning-memory ability in both MWM and ORT.. PDAPPV717I transgenic mice with an age range 4-16 months revealed the existence of learning-memory deficit compared with the control group. Tetrahydroxystilbene glucoside not only prevents, i.e. at an early stage, the learning-memory deficit in AD-like model, but also can reverse the learning-memory deficit in the late stage of AD-like model. Thus, TSG could be considered among the future therapeutic drugs indicated for the treatment of AD.

Topics: Age Factors; Aging; Alzheimer Disease; Amyloid beta-Protein Precursor; Analysis of Variance; Animals; Disease Models, Animal; Glucosides; Learning Disabilities; Maze Learning; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pattern Recognition, Visual; Stilbenes