Animals ; Diabetes Mellitus, Experimental ; drug therapy ; Insulin Resistance ; Stilbenes ; pharmacology ; therapeutic use

Humans ; Inflammation ; drug therapy ; metabolism ; MicroRNAs ; metabolism ; Stilbenes ; pharmacology ; therapeutic use

Vascular disrupting agents (VDAs) have presented a new kind of anti-cancer drug in recent years. VDAs take advantage of the weakness of established tumor endothelial cells and their supporting structures. In contrast to anti-angiogenic therapy, which inhibits the outgrowth of new blood vessels, vascular targeting treatments selectively attack the existing tumor vasculature. Here we summarized the anti-tumor activities, mechanisms and clinical applications of small molecule VDAs.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; therapeutic use ; Animals ; Antineoplastic Agents ; chemistry ; pharmacology ; therapeutic use ; Bibenzyls ; chemistry ; pharmacology ; therapeutic use ; Diphosphates ; chemistry ; pharmacology ; therapeutic use ; Endothelial Cells ; drug effects ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; pathology ; Neovascularization, Pathologic ; Oligopeptides ; chemistry ; pharmacology ; therapeutic use ; Organophosphorus Compounds ; chemistry ; pharmacology ; therapeutic use ; Serine ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Stilbenes ; chemistry ; pharmacology ; therapeutic use ; Tubulin Modulators ; chemistry ; pharmacology ; therapeutic use ; Xanthones ; chemistry ; pharmacology ; therapeutic use

OBJECTIVETo develop a composite material containing human hair keratin (HHK), collagen sponge (inner layer) and poly 2-hydroxyethyl methacrylate (PHEMA) film that allows sustained release of polydatin and test its effect as a biological dressing in promoting burn wound healing in SD rats.

METHODSThree HHK materials with fast, moderate, and low degradation rates were mixed at the ratio of 4:3:3 to prepare a reticular structure, which was processed into a composite material with bovine tendon-derived collagen sponge, and further complexed with HEMA film containing PD prepared by polymerization. Degree II burn wound was induced in SD rats by scalding and within postburn day 2-5, the wounds were cleansed and covered with the composite material or with glutaraldehyde-treated porcine skin (positive control). At week 1, 2, 4, 6 and 8 following wound dressing, 6 full-thickness skin samples were harvested from the wounds for histological observation and immunohistochemical detection of collagen and elastic fibers, and the wound healing time and healing rate were recorded.

RESULTSThe prepared collagen sponge film was transparent and porous (50-300 microm in diameter) and allowed sustained PD release into normal saline within 48 h. Compared with the porcine skin, the composite material reduced exudation and maintained ideal moisture of the wound, and significantly shortened the wound healing time (P=0.000). On day 7, 14, and 21 following dressing, the composite material and porcine skin significantly increased the wound healing rate as compared with the negative control group (P=0.000), and on day 14, the composite achieved significantly greater healing rate than the porcine skin (P<0.05).

CONCLUSIONHHK-collagen sponge-PHEMA/PD composite as a dressing material promotes burn wound healing in rats by allowing in vivo construction of tissue engineered epidermis. PHEMA is feasible for sustained drug delivery in this composite.

Animals ; Biological Dressings ; Burns ; drug therapy ; Cattle ; Collagen ; therapeutic use ; Drug Delivery Systems ; Drugs, Chinese Herbal ; pharmacology ; Glucosides ; pharmacology ; Humans ; Keratins ; therapeutic use ; Polyhydroxyethyl Methacrylate ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; pharmacology ; Swine ; Tissue Engineering ; Wound Healing

OBJECTIVE: To investigate the neuroprotective mechanism of tetrahydroxystilbene glucoside (TSG), a Chinese medicine, on rats after cerebral ischemia-reperfusion. METHODS: A total of 96 Sprague-Dawley male rats were divided into 4 groups (n=24): a control group, an ischemia-reperfusion (I/R) model group, a low dose TSG [60 mg/(kg.d)]group, and a high dose TSG [120 mg/(kg.d)]group. After 6 days intragastric (ig) administration of TSG or natural saline (I/R group), reversible middle cerebral artery occlusion (MCAO) model was established by intraluminal suture technique. The rats of control group were operated on while the middle cerebral artery was not blocked. At 6 h, 24 h, 48 h, and 7 d after the reperfusion, behavior test was used to evaluate the neurological deficiency of each group. The protein expressions of nerve growth factor (NGF), growth associated protein (GAP)-43, and protein kinase A catalytic subunit (PKAc) in the cortex were measured by immunohistochemical method. RESULTS: Compared with the I/R group, the neurological defect scores of the 2 TSG groups were significantly lower except at 6 h after the reperfusion. Compared with the I/R group, the protein expression of NGF, GAP-43, and PKAc after the reperfusion of the 2 TSG groups increased significantly. CONCLUSION The protein expression of NGF may increase when treated with TSG after cerebral ischemia-reperfusion, which activates the PKA pathway and increases the protein expression of GAP-43 that protects the neuron.
Animals ; GAP-43 Protein ; metabolism ; Glucosides ; pharmacology ; therapeutic use ; Infarction, Middle Cerebral Artery ; complications ; drug therapy ; Male ; Nerve Growth Factor ; metabolism ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Stilbenes ; pharmacology ; therapeutic use

Thyroid carcinogenesis is accompanied by loss of thyroid-specific functions and refractory to radioiodine and thyroid stimulating hormone (TSH) suppression therapy. Redifferentiating agents have been shown to inhibit tumor growth and improve the response to conventional therapy. Polyphenol phytochemicals (PPs) in fruits and vegetables have been reported to inhibit cancer initiation, promotion, progression and induce redifferentiation in selected types. In this study we examined PPs induce redifferentiation in thyroid cancer cell lines. We investigated the effects of genistein, resveratrol, quercetin, kaempferol, and resorcinol on the F9 embryonal carcinoma cell differentiation model. The thyroid cancer cell lines, TPC-1, FTC-133, NPA, FRO, and ARO, displayed growth inhibition in response to genistein, resveratrol, quercetin. We further demonstrated that genistein decreased the dedifferention marker CD97 in NPA cells and resveratrol decreased CD97 in FTC-133, NPA, FRO cells and quercetin decreased CD97 in all cell lines. We observed increased expression of differentiation marker NIS in FTC-133 cells in response to genistein, and resveratrol but no change in NPA, FRO, ARO cells. Quercetin increased or induced NIS in FTC-133, NPA, FRO cells. These findings suggest that PPs may provide a useful therapeutic intervention in thyroid cancer redifferentiation therapy.
Antigens, CD/metabolism ; Antineoplastic Agents/*pharmacology/therapeutic use ; Carcinoma, Embryonal/*drug therapy/metabolism ; Cell Differentiation/*drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Flavonoids/*pharmacology/therapeutic use ; Gene Expression Regulation, Neoplastic ; Genistein/pharmacology/therapeutic use ; Humans ; Kaempferols/pharmacology/therapeutic use ; Models, Biological ; Phenols/*pharmacology/therapeutic use ; Quercetin/pharmacology/therapeutic use ; Resorcinols/pharmacology/therapeutic use ; Stilbenes/pharmacology/therapeutic use ; Symporters/metabolism ; Thyroid Neoplasms/*drug therapy/metabolism

OBJECTIVEInflammation serves as the initial pathologic step of cardiovascular diseases including atherosclerosis. Resveratrol possesses many pharmacological properties including antioxidant, cardioprotective and anti-cancer effects. In this study, we investigate the anti-inflammatory effect and mechanisms of resveratrol in an atherosclerotic rabbit model.

METHODSRabbit were assigned to six groups (n = 10 each): control, high fat diet group, resveratrol low, medium and high dose groups, resveratrol pretreatment group. The serum tumor necrosis factor-α (TNF- α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were analyzed by Enzyme-linked immuno sorbent assay(ELISA). Phosphorylation levels of mitogen-activated protein kinases (MAPKs) cascades and NF-κB were determined by Western blot.

RESULTSCompared with the control group, the expression of serum inflammatory factors IL-1β, IL-6, TNF-α were increased in high-fat group (all P < 0.05). Compared with high-fat group, the expressions of IL-6, IL-1β, TNF-α were significantly reduced in resveratrol low, medium, high dose groups and resveratrol pretreatment group (all P < 0.01), and this effect is dose-dependent. In addition, the NF-κB, p38MAPK, JNK, ERK1/2 protein phosphorylation in high-fat group were significantly upregulated compared with control group (P < 0.05), which (except ERK1/2 phosphorylation level) were significantly downregulated in resveratrol treatment group and resveratrol pretreatment group.

CONCLUSIONThis study indicates that resveratrol reduces serum inflammatory cytokines in this atherosclerotic rabbit model via down-regulation phosphorylation of NF-κB, and MAPKs signaling, which might serve as the anti-inflammatory molecular basis of resveratrol.

Animals ; Atherosclerosis ; drug therapy ; metabolism ; Disease Models, Animal ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Male ; Mitogen-Activated Protein Kinases ; metabolism ; NF-kappa B ; metabolism ; Phosphorylation ; Rabbits ; Signal Transduction ; drug effects ; Stilbenes ; pharmacology ; therapeutic use ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo study the regulation trend of resveratrol on TNF-alpha, IL-1beta, IL-6 expressions in bronchoalveolar layage fluid (BALF) of RSV-infected BALB/c mice at different time points.

METHODRSV-induced BALB/c mice were orally administered with resveratrol. Their BALFs were collected at 24, 72 and 144 h after the first nasal drip with RSV to detect the level of TNF-alpha, IL-1P3, IL-6 by EILSA.

RESULTThe expression of TNF-alpha, IL-1Pf and IL-6 in BALF increased significantly compared with the normal group (P <0. 01) after 24 hours of RSV infection, while the expression of TNF-alpha (P < 0.01), IL-1beta (P < 0.05), IL-6 (P < 0.01) in the resveratrol group decreased notably compared with the model group. After 72 hours of infection with RSV, although the expression of TNF-alpha (P < 0.05), IL-1beta (P < 0.01) and IL-6 (P < 0.01) in BALF in model group were higher than those in the normal group, they were much more lower than at 24 h. The expression of IL-1beta and IL-6 (P < 0.05) in the resveratrol groups were down-regulated significantly, but no difference had been shown in TNF-alpha expression compared with the RSV infection group. After infection with RSV for 144 h, the expression of IL-1beta (P < 0.01) and IL-6 (P < 0.05) in BALF in the model group were higher than those in the normal group, but there was no difference in the secretion of TNF-alpha. The expression of TNF-alpha, IL-1beta and IL-6 showed also no remarkable difference between the resveratrol groups and the RSV infection group.

CONCLUSIONResveratrol can inhibit the over expression of inflammatory factors TNF-alpha, IL-1beta, IL-6 in bronchoalveolar lavage fluid of RSV-induced BALB/c mice and keep them at a low level with the passing of infection time.

Animals ; Bronchoalveolar Lavage Fluid ; immunology ; Female ; Interleukin-1beta ; analysis ; Interleukin-6 ; analysis ; Mice ; Mice, Inbred BALB C ; Respiratory Syncytial Virus Infections ; drug therapy ; immunology ; Stilbenes ; pharmacology ; therapeutic use ; Tumor Necrosis Factor-alpha ; analysis

BACKGROUNDPrevention of osteonecrosis (ON) has seldom been addressed. The purpose of this study was to evaluate the effect of resveratrol on preventing steroid-induced ON in rabbits.

METHODSSeventy-two rabbits were divided into four groups: (1) NEC (ON) group: thirty rabbits were treated with lipopolysaccharide (LPS) once, then with methylprednisolone (MPS) daily for 3 days; (2) PRE (prevention) group: thirty rabbits were given one dose of LPS, then MPS daily for 3 days, and resveratrol on day 0 and daily for 2 weeks; (3) RES (resveratrol) group: six rabbits were given resveratrol for 2 weeks but without LPS/MPS; (4) CON (control) group: six rabbits were given alcohol for 2 weeks but without LPS/MPS. Levels of plasma tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), thrombomodulin (TM), vascular endothelial growth factor (VEGF), maximum enhancement (ME) by magnetic resonance imaging, and ON incidence were evaluated.

RESULTSThe PRE group had a lower ON incidence than the NEC group, but with no significant differences at 2 weeks and 12 weeks. The RES and CON groups did not develop ON. TM and VEGF were significantly higher in the NEC group compared with the PRE group at weeks 1, 2, and 4 (TM: 1 week, P = 0.029; 2 weeks, P = 0.005; and 4 weeks, P = 0.047; VEGF: 1 week, P = 0.039; 2 weeks, P = 0.021; 4 weeks, P = 0.014), but the difference disappeared at 12 weeks. The levels of t-PA and PAI-1 were not significantly different between the NEC and PRE groups. The TM, t-PA, PAI-1, and VEGF concentrations in the RES and CON groups did not change over time. Compared to the baseline, ME in the NEC group decreased significantly (P = 0.025) at week 1, increased significantly (P = 0.021) at week 2, and was decreased at week 12. The variance was insignificant in the PRE group.

CONCLUSIONSResveratrol may improve blood supply to bone in a rabbit model of ON of the femoral head via anti-inflammatory effects to protect the vascular endothelium and reduce thrombosis.

Animals ; Disease Models, Animal ; Femur Head Necrosis ; chemically induced ; prevention & control ; Lipopolysaccharides ; toxicity ; Magnetic Resonance Imaging ; Methylprednisolone ; toxicity ; Plasminogen Activator Inhibitor 1 ; blood ; Rabbits ; Stilbenes ; pharmacology ; therapeutic use ; Thrombomodulin ; blood ; Tissue Plasminogen Activator ; blood ; Vascular Endothelial Growth Factor A ; blood

OBJECTIVETo investigate the effects of TSG on the content of nitric oxide synthase and the expression of endothelium nitric oxide synthase in artery vessels of experimental atherosclerotic rats.

METHODThe atherosclerosis model of rat was made by feeding high grease food and injecting Vit D3. Sixty male rats were randomly divided into six groups: normal control; model control; TSG high dose; TSG middle dose; TSG low dose; Simvastatin. After 12 weeks, several aorta were randomly tested, and the model made was successful when we found plaque. And after six weeks of treatment, the levels of NOS in serum were measured with a biochemical method. The biochemical method was adopted to detect the content of nitric oxide synthase and half-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect eNOS and iNOS gene expression in artery vessels.

RESULTData of the study demonstrated that compared with model group, the activity of NOS and the gene expression of eNOS were increased remarkably, and however the gene expression of iNOS was reduced markedly in simvastatin group and TSG 60, 120 mg x kg(-1) x d(-1) group.

CONCLUSIONTSG can enhance the expression of eNOS gene and reduce the expression of iNOS gene in aorta vessels of experimental atherosclerotic rats, which may be one of the anti-atherosclerosis mechanisms of TSG.

Animals ; Arteries ; drug effects ; metabolism ; pathology ; Atherosclerosis ; drug therapy ; enzymology ; pathology ; Gene Expression Regulation, Enzymologic ; drug effects ; Glucosides ; pharmacology ; therapeutic use ; Male ; Nitric Oxide Synthase ; genetics ; metabolism ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Nitric Oxide Synthase Type III ; genetics ; metabolism ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; Stilbenes ; pharmacology ; therapeutic use