Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “STILBENES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,351 records · Page 75Linked to original sources
PubMed2004

Combretastatin A4 phosphate: background and current clinical status.

Combretastatin A4 phosphate (CA4P) represents the lead compound in a group of novel tubulin depolymerising agents being developed as vascular targeting agents (VTAs). VTAs are drugs that induce rapid and selective vascular dysfunction in tumours. CA4P is a water-soluble prodrug of the cis-stilbene CA4 originally isolated from the tree Combretum caffrum. Preclinical studies have shown that CA4P induces blood flow reductions and subsequent tumour cell death in a variety of preclinical models. Moreover, this activity has been linked to its ability to rapidly alter the morphology of immature endothelial cells by disrupting their tubulin cytoskeleton. Phase I clinical trials have established a maximum tolerated dose in the range 60-68 mg/m2 and in addition have established that significant changes to tumour perfusion can be achieved across a wide range of doses. The dose-limiting toxicities include tumour pain, ataxia and cardiovascular changes. The maximum tolerated dose was independent of schedule, indicating the absence of cumulative toxicity. Although unexpected from preclinical studies, some evidence of clinical response was seen using CA4P as a single modality. Based on the Phase I data, combination studies of CA4P with established therapies are in progress and should determine whether the exciting preclinical data obtained when VTAs are used in combination with cytotoxic chemotherapy, radiation, radioimmunotherapy and even antiangiogenic agents, can be translated into man.

Animals↗
PubMedDate not supplied

Mechanisms of photoisomerization of polyenes in confined media: from organic glasses to protein binding cavities.

Photochemical reactivities of model organic systems (stilbene and diphenylbutadiene) in organic glasses were first examined and compared with those in solution and in organized media. These observations were in turn compared with reactivities of polyene chromophores in protein binding cavities (specifically PYP, rhodopsin and bacteriorhodopsin). The obvious conclusion is that the preference for the most volume-conserving Hula-twist mechanism isomerization in organic glasses is because of the close interaction between the guest and the host molecules. In organized media (zeolites, crystals and protein binding cavities), the residual empty space coupled with any specific guest-host interactions that are characteristic of a given system, could lead to involvement of the more volume-demanding one-bond-flip (i.e. torsional relaxation) or bicycle-pedal or an extended HT process in photoisomerization.

Bacterial Proteins↗
PubMed1991

Nutritional and toxicological evaluations of kochia hay (Kochia scoparia) fed to lambs.

Kochia foliage that had tested positive to Dragendorff's reagent (presumptive alkaloids) and had elicited chronic toxicosis when fed to rats was fed to sheep to characterize early stages of kochia toxicosis and evaluate treatments that might improve tolerance. Twelve fine-wool lambs (46 +/- 9 kg BW) were fed chopped kochia hay (35%) mixed with chopped alfalfa hay (65%) for 4 wk. The kochia diet had 14.3% CP and 39.9% ADF. Dry matter intake averaged 3.4% of BW/d. Body weight did not change during 4 wk and blood serum components were not changed from values at the onset. Thereafter, kochia was increased to 50% of diet for five more weeks, during which four treatments were imposed randomly (three lambs/treatment): 1) none; 2) N-acetyl-L-cysteine plus trans-stilbene oxide, 21 and 52 mg/kg of BW, respectively, given i.p. twice weekly; 3) retinyl palmitate, 275 mg, plus alpha-tocopherol, 300 mg/lamb dosed i.m. twice weekly; and 4) zinc sulfate mixed in the feed to provide 500 mg daily. Kochia contained 4.8% oxalate. The diet with 50% kochia had 16% CP and 36% ADF, and digestibility coefficients were 59% for DM, 72% for CP, and 59% for ADF. After 5 wk, blood glucose was elevated slightly, total bilirubin was increased about 1.5-fold (P less than .05), alanine aminotransferase was elevated slightly (P less than .05), and inorganic phosphorus and urea (blood urea N) were diminished (P less than .05); other serum components, including calcium, were unchanged from initial levels (P greater than .10). Treatments had negligible effects for modifying serum signs of mild chronic toxicosis associated with kochia hay fed as 50% of diet.

Acetylcysteine↗
PubMed1991

Altered metabolic hormones, impaired nitrogen retention, and hepatotoxicosis in lambs fed Kochia scoparia hay.

Livestock grazing lush Kochia scoparia (L.) Schrad, sometimes experience BW loss, hyperbilirubinemia, photosensitization, and polyuria. Animals fed kochia hay may exhibit milder or negligible signs of toxicosis but fail to utilize nutrients efficiently. To characterize early aspects of kochia toxicosis and to evaluate prospective treatments, 12 wether lambs (34 +/- 3 kg) were fed prebloom kochia hay (83% OM, 15% CP, and 6.3% total oxalate) and treated as follows: 1) no treatment; 2) drenched daily with aqueous ZnSO4 to provide 30 mg of Zn/kg of BW); 3) injected i.p. twice weekly with N-acetyl-L-cysteine (CYS) in saline (21 mg/kg of BW) plus trans-stilbene oxide (TSO) in corn oil (27 mg/kg of BW); and 4) treated as 2) plus 3). Treatments were imposed factorially (2 x 2) with three lambs per treatment. Kochia intake (ad libitum) averaged .57 kg/d (1.7% of BW) for 80 d, and digestibility of DM and CP were 44 and 59%, respectively, at wk 4, but BW loss was severe (6 to 11 kg/lamb). After 14 d, serum insulin and prolactin were decreased (P less than .05) below initial values (.48 to .11 and 102 to 28 ng/ml, respectively). Serum somatotropin increased (P less than .05) from 4.5 to 6.8 ng/ml at 4 wk. Serum total bilirubin increased threefold at 3 wk (P less than .05) and declined slightly thereafter through 10 wk. Early changes in serum enzymes reflected mild hepatotoxicosis without cholestasis, whereas histopathology (at 80 d) showed diffuse hepatocyte swelling and nephrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1990

Bicarbonate and DIDS effects on intracellular potential difference in rabbit ciliary epithelium.

A change of [HCO3-] in the solution bathing isolated rabbit ciliary epithelium from 30 mM to 0, or vice versa, resulted in a change of intracellular electrical potential difference (PDI) of 7 mV. Intermediate [HCO3-] (5, 10 and 15 mM) solutions were also tested. No perceivable change of PDI occurred when [HCO3-] changed from 30 to 15 mM. PDI depolarized gradually when [HCO3-] decreased from 30 or 15 mM to 0 mM, but PDI hyperpolarized at a faster rate when [HCO3-] increased from 0 to 15 or 30 mM. The amount of change of PDI from 15 to 5 mM, or vice versa, and from 10 to 0 mM or vice versa, was 4 mV. The stilbene, DIDS (10(-4) M), hyperpolarized the PDI in HCO3(-)-rich solutions. The response of DIDS was reduced in HCO3(-)-free medium and inhibited in Cl(-)-free solution. The results suggest the existence of an electrogenic bicarbonate transport or Na+/HCO3- cotransport system.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

Resveratrol attenuates ovariectomy-induced hypertension and bone loss in stroke-prone spontaneously hypertensive rats.

We examined the effect of resveratrol (3,4',5-trihydroxy stilbene), a phenolic compound found in the skins of most grapes, on blood pressure and bone loss in ovariectomized (OVX), stroke-prone spontaneously hypertensive rats (SHRSP). Nineteen-week-old female SHRSP were divided into a sham-ovariectomized (sham) group fed a control diet and two OVX groups fed either a control diet (OVX-Cont) or a diet supplemented with resveratrol (5 mg/kg per d; OVX-Resv). Ovariectomy induced significant increases in systolic blood pressure (SBP). Resveratrol lowered the SBP by 15%) by the third week of administration, and this effect was maintained throughout the study. Resveratrol treatment also significantly enhanced endothelium-dependent vascular relaxation in response to acetylcholine (ACh) in OVX rats. Finally, femur breaking energies measured for the resveratrol-treated (OVX-Resv) group were significantly higher than those of the resveratrol-untreated (OVX-Cont) group. While no significant differences in calcium, magnesium and phosphorus content were found between the femurs of OVX-Cont and OVX-Resv rats, the femur hydroxyproline content in the OVX-Resv group was significantly higher than of the OVX-Cont group. We conclude that, in OVX-SHRSP, resveratrol acts by a similar mechanism to mammalian estrogens, lowering blood pressure by increasing dilatory responses to ACh. The present study also demonstrated that resveratrol was able to prevent ovariectomy-induced decreases in femoral bone strength.

Animals↗
PubMed2001

Mechanism of cardioprotection by resveratrol, a phenolic antioxidant present in red wine (Review).

Coronary heart disease (CHD) has been and remains a major contributor to morbidity and mortality in developed countries. The most common form of CHD in the western world is atherosclerosis (AS), especially of the major coronary arteries. Failure to maintain an intact endothelium, as a result of episodic and/or persistent injury and perturbation of the vascular endothelium, promotes formation of fatty streaks which are considered initiation events of AS. Cellular constituents contributing to endothelial injury include endothelial cells, monocytes, platelets, and smooth muscle cells. Individuals diagnosed with AS face complex, enduring clinical complications and enormous medical costs. Simple and easily compliant prevention and treatment measures are therefore strategic considerations in the management of this vascular disease. Based on known risk factors for CHD, priorities in AS prevention should include smoking cessation, blood pressure control, and diet modification. In recent years, the possible benefits of low to moderate consumption of alcoholic beverages, particularly of red wine, in the prevention of heart disease has received increasing attention and debate in the popular media as well as in the scientific community. Such attention has been prompted by research findings supporting a relationship between red wine consumption and the French paradox. This phenomenon refers to people residing in certain parts of France where red wine is customarily consumed during meals having a low CHD mortality, despite living a lifestyle considered to have comparably high CHD risks, as those in the US and many other developed countries. Studies have reported that the cardioprotective effects of red wine are greater than those attributed solely to ethanol and other types of alcoholic beverages. The mechanism(s) underlying the greater CHD protective benefits of red wine have not been elucidated. Recently the polyphenol resveratrol (3,5,4'-trihydroxy-trans-stilbene), known to be abundantly present in red wine, compared to white wine, beer, or spirits, has been demonstrated to elicit a broad spectrum of biological responses in in vitro and in animal studies, including effects that are compatible with the cardioprotective roles proposed for red wine. These recently described effects of resveratrol will be reviewed in this article. We will first summarize published data showing an inverse association between consumption of alcoholic beverages/red wine and risk of CHD. A review of biosynthesis of resveratrol and its presence in food groups and wines will follow. Recent studies relating exposure to wine/resveratrol with reduction in myocardial damage during ischemia-reperfusion, modulation of vascular cell functions, inhibition of LDL oxidation, and suppression of platelet aggregation will be presented. The last section of this review will focus on a discussion of mechanism(s) by which resveratrol acts as a potential cardioprotective agent.

Animals↗
PubMed2001

Antioxidant activity of resveratrol compared with common food additives.

Resveratrol is a phenolic compound of the stilbene family present in wines and various parts of the grape, including the skin. In this study, the antioxidant and prooxidant activities of resveratrol were compared with other antioxidants (butylated hydroxytoluene [BHT], butylated hydroxyacetone [BHA], phenol, propyl gallate [PG], sodium tripolyphosphate [TPP], alpha-tocopherol, and vanillin) widely used in foods. The ability of these compounds to inhibit lipid peroxidation was as follows: BHA > resveratrol > PG > tripolyphosphate > vanillin > phenol > BHT > alpha-tocopherol, the first three inhibiting the peroxidation in a concentration-dependent manner. The order of OH* scavenger activity of the tested compounds was BHA > TPP > BHT. Resveratrol and vanillin produced between 10 to 7% and 16 to 10% inhibition of the deoxyribose attack, respectively, but they do not scavenge OH*. Neither the resveratrol analyzed nor PG or the rest of compounds reacted with H202 and must be considered inefficient in catalyzing any subsequent oxidation. The ability to scavenge HOCI was, in decreasing order, PG > resveratrol > alpha-tocopherol > phenol. The other compounds did not scavenge HOCl.

Antioxidants↗
PubMed1998

Antineoplastic agents 393. Synthesis of the trans-isomer of combretastatin A-4 prodrug.

The (E)-stilbene isomer (2a) of the (Z)-combretastatin A-4 prodrug (1b) was efficiently prepared from (E)-combretastatin A-4 by a reaction sequence employing phosphorylation (dibenzyl chlorophosphite), cleavage (trimethyliodosilane) of the benzyl ester and reaction of the resulting phosphoric acid with sodium methoxide. The sodium phosphate product (2c) was also found to be an important side-product, presumably from iodine-catalyzed isomerization, when the analogous synthetic route was used to obtain the combretastatin A-4 prodrug (1b). The phosphoric acid precursor of prodrug 1b derived from (Z)-combretastatin A-4 (1a) was converted into a series of metal cation and ammonium cation salts to evaluate effects on human cancer cell growth, antimicrobial activities and solubility behavior.

Animals↗
PubMed1999

Cancer chemopreventive activity of resveratrol.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a naturally occurring compound shown to inhibit carcinogen-induced preneoplastic lesion formation in mouse mammary organ culture and tumorigenesis in the two-stage mouse skin model. Cancer chemopreventive potential was also suggested in various assays reflective of the three major stages of carcinogenesis. Anti-initiation activity was indicated by its antioxidant and antimutagenic effects, inhibition of the hydroperoxidase function of cyclooxygenase (COX), and induction of phase II drug-metabolizing enzymes. Antipromotion activity was indicated by antiinflammatory effects, inhibition of production of arachidonic acid metabolites catalyzed by either COX-1 or COX-2, and chemical carcinogen-induced neoplastic transformation of mouse embryo fibroblasts. Antiprogression activity was demonstrated by its ability to induce human promyelocytic leukemia (HL-60) cell differentiation. Moreover, pretreatment of mouse skin with resveratrol significantly counteracted 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress, as evidenced by numerous biochemical responses. Resveratrol reduced the generation of hydrogen peroxide, and normalized levels of myeloperoxidase and oxidized-glutathione reductase activities. It also restored glutathione levels and superoxide dismutase activity. As judged by the reverse transcriptase-polymerase chain reaction, resveratrol selectively inhibited TPA-induced expression of c-fos and transforming growth factor-beta 1 (TGF-beta 1), but did not affect other TPA-induced gene products including COX-1, COX-2, c-myc, c-jun, and tumor necrosis factor-alpha. These data indicate that resveratrol may interfere with reactive oxidant pathways and/or modulate the expression of c-fos and TGF-beta 1 to inhibit tumorigenesis in mouse skin. As reported herein, in addition to the activities described above, resveratrol inhibited the de novo formation of inducible nitric oxide synthase (iNOS) in mouse macrophages stimulated with lipopolysaccharide. This finding suggests an additional mechanism by which resveratrol may function as a cancer chemopreventive agent.

Animals↗
PubMed1998

Identification and measurement of resveratrol and formaldehyde in parts of white and blue grape berries.

The phytoalexin resveratrol (3,5,4'-trihydroxy-trans-stilbene) and formaldehyde (as its dimedone adduct, formaldemethone) have been identified and measured in the extracts of parts of white and blue grapes as well as in white and red wines by overpressured layer chromatography (OPLC), high performance liquid chromatography (HPLC) and from matrix assisted laser desorption/ionization mass spectrometric data. It has been established that the level of resveratrol was very high in skin and in some cases in the stem. Blue grape varieties and red wines always contained a considerably higher amount of resveratrol than white grapes and wines. The measurable level of formaldehyde as well as the resveratrol content was always parallelly high in the same parts of the berries, however, the formaldehyde level was higher in white grapes than in blue ones. The simultaneous occurrence of resveratrol and formaldehyde gives a possibility for interaction between these two special molecules, consequently, hydroxymethyl derivatives of resveratrol can be formed. These resveratrol derivatives may be responsible for special biological activities of resveratrol in grapes and dietetically (cardioprotective effect and chemopreventive effect against cancer) in the human organism.

Chromatography, High Pressure Liquid↗
PubMed1999

Inhibitory effect of piceatannol, a protein tyrosine kinase inhibitor, on asexual maturation of Plasmodium falciparum.

This report describes the effect of piceatannol (3,4,3',5'-tetrahydroxy trans stilbene), a plant secondary natural product, on protein tyrosine kinase (PTK) activity in different stages of P. falciparum grown in vitro. Piceatannol inhibited PTK activity in trophozoites and schizonts suggesting that PTK may be important in the initial asexual maturation of the parasite. Inhibition of PTK activity by piceatannol may thus provide new insights into more specific tools for chemotherapeutic interventions for P. falciparum.

Animals↗
PubMed1975

Photocarcinogenesis: lack of enhancement by fluorescent white agents.

These studies were designed to determine whether fluorescent whitening agents (FWAs) could: (I) produce an augmented acute response of skin to a single ultraviolet light exposure (i.e., phototoxicity), or (II) increase the number or hasten the appearance of skin tumors after several ultraviolet light exposures (i.e., chemically enhanced photocarcinogenesis). Five substituted stilbene FWAs were screened for phototoxicity. The results of pretreatment with these agents were compared with pretreatment by a known photoxic agent, 8-methoxypsoralen (8-MOP) or the vehicle (methanol) using the skin of hairless mice, miniature pigs, and man. None of the FWAs was phototoxic. Photocarcinogenesis testing involved pretreating hairless mouse skin with FWAs, 8-MOP, or methanol only before each daily exposure to simulated solar ultraviolet light. In terms of tumor yield and tumor development time, photocarcinogenesis was enhanced by 8-MOP, but not by FWAs.

Animals↗
PubMed1997

[Chemical constituents of the leaves of Ginkgo biloba].

Four compounds were isolated from ethyl acetate extract of the leaves of Ginkgo biloba. Compounds II, III, IV were identified as ginkgolides A, B and C respectively, Compound I, which was obtained from the leaves of G. biloba for the first time, was identified as 3,3'-dimethoxy-4,4'-dihydroxy-stilbene by spectroscopic methods.

Diterpenes↗
PubMed2000

Activation of cytochrome P450 gene expression in the rat brain by phenobarbital-like inducers.

Oxidative biotransformation, coupled with genetic variability in enzyme expression, has been the focus of hypotheses interrelating environmental and genetic factors in the etiology of central nervous system disease processes. Chemical modulation of cerebral cytochrome P450 (P450) monooxygenase expression character may be an important determinant of in situ metabolism, neuroendocrine homeostasis, and/or central nervous system toxicity resulting from exposure to neuroactive drugs and xenobiotic substances. To examine the capacity of the rat brain to undergo phenobarbital (PB)-mediated induction, we developed reverse transcription-polymerase chain reaction methods and evaluated the effects of several PB-like inducers on P450 and microsomal epoxide hydrolase gene expression. Animals treated i.p. with four daily doses of PB demonstrated markedly induced levels of CYP2B1, CYP2B2, and CYP3A1 mRNA in the striatum and cerebellum. In contrast, 1 or 2 days of PB treatment resulted in unchanged or even slightly decreased levels of CYP2B1 and CYP2B2 in the brain, although the latter treatments produced marked induction of the corresponding genes in the liver. Only slight increases in epoxide hydrolase RNA levels resulted in brains of PB-treated animals. Substantial activation of cerebral CYP2B1, CYP2B2, and CYP3A1 mRNA levels also resulted when animals were treated with the neuroactive drugs diphenylhydantoin and amitryptiline, and with the potential PB-like xenobiotic inducers trans-stilbene oxide and diallyl sulfide, whereas dichlorodiphenyltrichloroethane was less efficacious. Although the time course of the induction response is delayed in brain relative to that required for the liver, these results clearly establish that brain P450s are markedly PB inducible.

Allyl Compounds↗
PubMed2000

Antineoplastic agents 429. Syntheses of the combretastatin A-1 and combretastatin B-1 prodrugs.

The original synthesis of combretastatin A-1 (1) was modified to allow an efficient scale-up procedure for obtaining this anti-neoplastic stilbene. Subsequent conversion to a useful prodrug was accomplished by diphosphorylation (to 10), with in situ formation of dibenzylchlorophosphite, followed by cleavage of the benzyl ester protecting groups with trimethyliodosilane. The phosphoric acid intermediate was treated with sodium methoxide to complete a practical route to the sodium phosphate prodrug (4). Selective hydrogenation of phosphate 10 and treatment of the product with sodium methoxide led to combretastatin B-1 prodrug (5). The phosphoric acid precursor of prodrug 4 was employed in a parallel series of reactions to produce a selection of metal and ammonium cation prodrug candidates. Each of the phosphate salts was evaluated from the perspective of relative solubility behavior and cancer cell growth inhibition. The sodium phosphate prodrug of combretastatin A-1 (4) was selected for detailed antineoplastic studies.

Animals↗
PubMedDate not supplied

Inhibitory effects of active substances isolated from Cassia garrettiana heartwood on tumor growth and lung metastasis in Lewis lung carcinoma-bearing mice (Part 2).

Previously, we reported that a methanol extract (500 mg/kg x 2/day) of the heartwood of Cassia garrettiana inhibited the tumor growth and metastasis to the lung in Lewis lung carcinoma (LLC)-bearing mice. Furthermore, we isolated the two active substances from the methanol extract of C. garrettiana and identified compound 1 as cassigarol A. In the present study, compound 2 was identified as 3, 3', 4, 5'-tetrahydroxy stilbene (piceatannol) based on the 1H-NMR spectral data and products formed by oxidation with potassium permanganate. We examined the active substance (compound 2, piceatannol) and its acetylated derivative on the tumor growth and lung metastasis in LLC-bearing and carcinectomized mice. Piceatannol (50 mg and 100 mg/kg x 2/day) did not affect the tumor growth, while piceatannol acetate (50 mg and 100 mg/kg x 2/day) significantly inhibited the tumor growth. Piceatannol and its derivative piceatannol acetate inhibited the metastasis to the lung dose-dependently in carcinectomized mice. Moreover, piceatannol and piceatannol acetate prolonged the survival time and increased the survival rate in carcinectomized mice. In addition, piceatannol inhibited the formation of capillary-like networks of human umbilical vein endothelial cells (HUVECs) at the concentrations of 10 to 100 microM, but its acetylated derivative did not. Therefore, it is suggested that the antimetastatic activities of piceatannol might be due to the inhibition of tube formation (angiogenesis) of HUVECs.

Acetylation↗