pinostilbene and pterostilbene

Tight junctions (TJs) are a member of the intestinal epithelium barrier that provides the first line of protection against external factors. Anti-obesity and protective effects of pterostilbene (PSB) on TJs have previously been reported, but the effect of its colonic metabolite, pinostilbene (PIN), is less understood.. A 16-week animal model feed with western-diet to induce colonic TJs disruption is designed, supplemented with PSB and PIN to evaluate their potent in colonic TJ protection. The results show that both PSB and PIN exert suppressive effects on obesity, hepatic steatosis, and chronic inflammation in western-diet-fed mice. Western-diet feeding significantly reduces expression of TJ proteins, including ZO-1, occludin, and claudin-1, while PSB and PIN supplementation effectively protects TJ proteins against disruption. Increment in serum, hepatic, and mesenteric pro-inflammatory cytokines suggests their probable involvement in TJ disruption supported with the findings in macrophage polarization. The adverse are revered by PSB and PIN. The protective effect of PSB and PIN on TJ proteins may stem from their anti-inflammation capabilities.. This is the first study suggesting that PIN, the metabolite of PSB, demonstrates a similar protective effect on colonic TJ proteins via its anti-obesity, hepatic protection, and anti-inflammatory capabilities.

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Diet, Western; Intestinal Mucosa; Mice; Occludin; Stilbenes; Tight Junctions

Resveratrol and its methyl ethers, which belong to a class of natural polyphenol stilbenes, play important roles as biologically active compounds in plant defense as well as in human health. Although the biosynthetic pathway of resveratrol has been fully elucidated, the characterization of resveratrol-specific O-methyltransferases remains elusive. In this study, we used RNA-seq analysis to identify a putative aromatic O-methyltransferase gene, AcOMT1, in Acorus calamus. Recombinant AcOMT1 expressed in Escherichia coli showed high 4'-O-methylation activity toward resveratrol and its derivative, isorhapontigenin. We purified a reaction product enzymatically formed from resveratrol by AcOMT1 and confirmed it as 4'-O-methylresveratrol (deoxyrhapontigenin). Resveratrol and isorhapontigenin were the most preferred substrates with apparent K

Topics: Acorus; Cloning, Molecular; Kinetics; Methylation; Methyltransferases; Plant Proteins; Resveratrol; Stilbenes

The flavin-dependent monooxygenase Sam5 was previously reported to be a bifunctional hydroxylase with a coumarte 3-hydroxylase and a resveratrol 3'-hydroxylase activity. In this article, we showed the Sam5 enzyme has 3'-hydroxylation activities for methylated resveratrol (pinostilbene and pterostilbene), hydroxylated resveratrol (oxyresveratrol) and glycosylated resveratrol (piceid) as substrates. However, the use of piceid, a glycone type stilbene, as a substrate for bioconversion experiments with the Sam5 enzyme expressed in,

Topics: Dinitrocresols; Escherichia coli; Flavins; Glucosides; Hydroxylation; Mixed Function Oxygenases; Plant Extracts; Resveratrol; Stilbenes

The stilbene compound resveratrol was glycosylated to give its 4'-O-β-D-glucoside as the major product in addition to its 3-O-β-D-glucoside by a plant glucosyltransferase from Phytolacca americana expressed in recombinant Escherichia coli. This enzyme transformed pterostilbene to its 4'-O-β-D-glucoside, and converted pinostilbene to its 4'-O-β-D-glucoside as a major product and its 3-O-β-D-glucoside as a minor product. An analysis of antioxidant capacity showed that the above stilbene glycosides had lower oxygen radical absorbance capacity (ORAC) values than those of the corresponding stilbene aglycones. The 3-O-β-D-glucoside of resveratrol showed the highest ORAC value among the stilbene glycosides tested, and pinostilbene had the highest value among the stilbene compounds. The tyrosinase inhibitory activities of the stilbene aglycones were improved by glycosylation; the stilbene glycosides had higher activities than the stilbene aglycones. Resveratrol 3-O-β-D-glucoside had the highest tyrosinase inhibitory activity among the stilbene compounds tested.

Topics: Agaricales; Biocatalysis; Chemistry Techniques, Synthetic; Enzyme Inhibitors; Glucosyltransferases; Glycosides; Glycosylation; Monophenol Monooxygenase; Oxygen Radical Absorbance Capacity; Resveratrol; Stilbenes

Topics: Hydrogen-Ion Concentration; Isomerism; Magnetic Resonance Spectroscopy; Octanols; Resveratrol; Solubility; Stilbenes; Water

Pterostilbene (PTE) is a resveratrol derivative mainly found in blueberries, and it has been shown to inhibit colon carcinogenesis in multiple animal models. To shed light on the mechanism of PTE in inhibiting colon carcinogenesis, we investigated the PTE metabolites in the mouse colon and in the human colon cancer cells.. CD-1 mice were fed PTE-containing diet for 3 weeks, and colonic content and colonic mucosa were collected and subjected to LC-MS analysis. Pinostilbene (PIN) was identified as a major metabolite of PTE in the mouse colon. Importantly, the level of PIN was found to be approximately equivalent to that of PTE in the colonic mucosa. PIN significantly inhibited the growth of human colon cancer cells, i.e., HCT116 and HT29. These inhibitory effects were similar to those produced by PTE. Moreover, under physiologically relevant conditions, 20 and 40 μM of PIN caused cell cycle arrest at S phase and induced apoptosis in colon cancer cells. These effects were associated with profound modulation of signaling proteins related with cell proliferation and programmed cell death.. Our results demonstrated that PIN is a major metabolite of PTE in the colon of mice fed with PTE, and PIN may play important roles in the anti-colon cancer effects elicited by orally administered PTE.

Topics: Administration, Oral; Animals; Apoptosis; Cell Line, Tumor; Colon; Colonic Neoplasms; HCT116 Cells; Humans; Inactivation, Metabolic; Male; Mice, Inbred Strains; S Phase Cell Cycle Checkpoints; Stilbenes

Stilbenoids, including resveratrol and its methylated derivatives, are natural potent antioxidants, produced by some plants in trace amounts as defense compounds. Extraction of stilbenoids from natural sources is costly due to their low abundance and often limited availability of the plant. Here we engineered the yeast Saccharomyces cerevisiae for production of stilbenoids on a simple mineral medium typically used for industrial production. We applied a pull-push-block strain engineering strategy that included overexpression of the resveratrol biosynthesis pathway, optimization of the electron transfer to the cytochrome P450 monooxygenase, increase of the precursors supply, and decrease of the pathway intermediates degradation. Fed-batch fermentation of the final strain resulted in a final titer of 800 mg l

Topics: Antioxidants; Arabidopsis Proteins; Bioreactors; Biosynthetic Pathways; Cytochrome P-450 Enzyme System; Fermentation; Malonyl Coenzyme A; Metabolic Engineering; Phenylalanine; Promoter Regions, Genetic; Resveratrol; Saccharomyces cerevisiae; Stilbenes

Resveratrol (3,4',5-trans-trihydroxystilbene) is a polyphenolic phytoalexin that belongs to a family of naturally occurring stilbenes. It has been reported that the health-promoting activities of certain methylated resveratrol derivatives are more effective than those of unmodified resveratrol. In this study, we isolated two candidate genes with resveratrol O-methyltransferase (ROMT) activity from grape (Vitis riparia) and sorghum (Sorghum bicolor). To assess their ROMT activities in vivo, we synthesized VrROMT and SbROMT3 following codon-optimization and expressed the VrROMTsyn and SbROMT3syn genes using a dual expression vector system. Furthermore, we attempted to produce pterostilbene from resveratrol as a substrate by the expression of two putative ROMT proteins in Escherichia coli. Unexpectedly, expression of the SbROMT3syn gene in E. coli led to the production of mono-methylated stilbene (3,4'-dihydroxy-5-methoxy-trans-stilbene, pinostilbene) from resveratrol compounds. However, a very small amount of di-methylated stilbene (3,5-dimethoxy-4'-hydroxy-trans-stilbene, pterostilbene) was also detected. Consistently, we found that in vitro methylation assays of resveratrol by recombinant SbROMT3syn produced pinostilbene as the major product besides a very small amount of pterostilbene. By contrast, very small amounts of methylated resveratrol derivatives were detected in E. coli expressing the VrROMTsyn protein. This suggests that the SbROMT3syn is more useful in the production of pinostilbene compounds than pterostilbene from resveratrol in E. coli.

Topics: Base Sequence; DNA, Plant; Escherichia coli; Gene Expression; Genes, Plant; Methylation; Methyltransferases; Molecular Sequence Data; Plant Proteins; Recombinant Proteins; Resveratrol; Sorghum; Stilbenes; Vitis

Stilbenes are phytoalexins that become activated when plants are stressed. These compounds exist in foods and are widely consumed. Resveratrol is a grape-derived stilbene, which possesses a wide range of health-promoting activities, including anticancer properties. Several other stilbenes structurally similar to resveratrol are also available in food, but their biological activities remain largely unknown. In this study, we compared the effects of resveratrol and its natural derivatives pterostilbene, trans-resveratrol trimethylether, trans-pinostilbene and trans-desoxyrhapontigenin on androgen-responsive human prostate cancer LNCaP cells. We found that these compounds exert differential effects on LNCaP cell growth, cell cycle and apoptosis. Trans-resveratrol trimethylether appeared to be the most potent compound among the stilbenes tested. Treatment of LNCaP cells with trans-resveratrol trimethylether resulted in G2/M blockage while other compounds, including resveratrol, induced G1/S arrest. Moreover, different from other compounds, trans-resveratrol trimethylether induced apoptosis. At the molecular level, the effects of these compounds on cell cycle correlated with induction of the cyclin-dependent kinase inhibitor 1A and B mRNA levels. Additionally, these compounds also inhibited both androgen- as well as estrogen-mediated pathways. These results provide mechanistic information on how resveratrol and its methylether analogs may act to contribute to potential antiprostate cancer activity.

Topics: Androgen Antagonists; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Dose-Response Relationship, Drug; Estrogen Antagonists; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Resveratrol; RNA, Messenger; Stilbenes; Structure-Activity Relationship

CYP1A1 and CYP1B1 are the inducible forms of cytochrome P450 expressed in extrahepatic tissues, which are responsible for the biotransformation of polycyclic aromatic hydrocarbons, heterocyclic amines and estradiol to the carcinogenic intermediates. The aim of our research was to determine and compare the inhibitory effect of naturally occurring analogues of trans-resveratrol on the catalytic activities of human recombinant CYP1A1 and CYP1B1. Pinostilbene (3,4'-dihydroxy-5-methoxystilbene), desoxyrhapontigenin (3,5-dihydroxy-4'-methoxystilbene), and pterostilbene (3,5-dimethoxy-4'-hydroxystilbene) appeared to be very potent inhibitors of CYP1A1 catalytic activity with Ki values of 0.13, 0.16 and 0.57 microM, respectively. Results from this study indicate that trans-resveratrol analogues in which the hydroxy groups are substituted by methoxy groups exhibit a remarkably stronger inhibitory effect towards CYP1A1 in comparison to the parent compound. On the contrary, the potency of pinostilbene, desoxyrhapontigenin and pterostilbene towards CYP1B1 with Ki values of 0.90, 2.06 and 0.91 microM, respectively, was comparable to that of resveratrol. It appears that between these analogues, inhibition of CYP1A1 and CYP1B1 catalytic activities does not vary much regardless of the number and position of methylether substitution. The results suggest that the trans-resveratrol analogues: pinostilbene, desoxyrhapontigenin and pterostilbene, which occur in some food plants, might be considered as promising chemopreventive agents.

Topics: Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP1B1; Enzyme Inhibitors; Humans; Methyl Ethers; Recombinant Proteins; Resveratrol; Stilbenes