United States of America, As Represented by the Secretary of Agriculture

The University of Mississippi

Rutgers, the State University of New Jersey

Agnes M Rimando

Scott R Baerson

Zhiqiang Pan

Wallace H Yokoyama

Dennis R Feller

Franck E Dayan

James A Joseph

Barbara Shukitt-Hale

Nanjoo Suh

James J Polashock

Abir El-Alfy

Md Al Rahim

Daniel Cook

Cassia Suemi Mizuno

Bandaru S Reddy

Abir El-Aify

We report for the first time that pterostilbene, a natural analog of resveratrol, shows anxiolytic-like action by downregulating phosphorylated levels of ERKs in the hippocampus of mice. Mice administered pterostilbene (1-10 mg/kg BW) by oral gavage were subjected to the Elevated-plus maze (EPM) test. Pterostilbene manifested anxiolytic activity at 1 and 2 mg/kg doses, demonstrated by an increase in percent permanence time and number of entries in open arms, critical determinants correlated with anxiety. This anxiolytic activity of pterostilbene was comparable to that of diazepam at 1 and 2 mg/kg in the EPM. The percent traveled distance and the percent permanence time in the enclosed arms were decreased with the 1 and 2 mg/kg doses. The 5 and 10 mg/kg doses did not show any anxiolytic effect. Locomotor activity was unaffected in all doses. Western blot analysis corroborated the observed behaviors in the EPM, revealing a decrease in both ERK1 and ERK2 phosphorylation in hippocampal homogenates from mice treated with 1 and 2 mg/kg doses; the 5 and 10 mg/kg doses showed no significant effect on the phosphorylation of ERKs. Pterostilbene was detected in serum and brain tissue following a single oral administration, demonstrating that the compound can cross the blood-brain barrier to reach the brain regions, including hippocampus, and thereby exert its anxiolytic effect. Resveratrol, the parent molecule of pterostilbene, did not have any anxiolytic effect.

Anxiolytic effect of pterostilbene

Sorghum is considered an allelopathic crop species and sorgoleone likely accounts for much of its allelopathic properties. Prior investigations into the biosynthesis of sorgoleone suggested the participation of one or more alkylresorcinol synthases (ARS), which are type III polyketide synthases (PKS) that produce 5-alkylresorcinols using medium to long-chain fatty acyl-CoA starter units via iterative condensations with malonyl-CoA. Quantitative real-time RT-PCR analysis of PKS-like sequences mined from isolated root hairs revealed that two sequences, designated ARS1 and ARS2, were preferentially expressed. Recombinant enzyme studies demonstrated that both sequences encode ARS enzymes capable of accepting a variety of fatty acyl-CoA starter units. RNA interference (RNAi) experiments directed against ARS1 and ARS2 resulted in the generation of multiple independent transformant events exhibiting dramatically reduced sorgoleone levels. Thus, both ARS1 and ARS2 participate in the biosynthesis of sorgoleone in planta. ARS1 and ARS2 sequences were used to identify rice genes encoding alkylresorcinol synthases.

Two alkylresorcinol synthase genes from sorghum; cloning, expression, transformation and characterization

Disclosed is a pharmaceutical composition for treating oxidative stress comprising a therapeutically effective amount of a substantially pure compound of pterostilbene and a physiologically acceptable carrier. Pterostilbene is administered in an amount between about 2.5 mg to about 10 mg per kilogram of subject body weight. Also disclosed is a method for increasing a working memory of a subject, the method comprising administrating an effective amount of a substantially pure compound of pterostilbene, wherein the working memory for a subject increase and the therapeutic effectiveness is about 10 mg of pterostilbene per kilogram of subject body weight.

Method improve spatial memory via pterostilbene administration

Method to ameliorate oxidative stress and improve working memory via pterostilbene administration

Stilbene compounds for the prevention and treatment of colon cancer or colon inflammation and methods of using same are provided.

Prevention and treatment of colon cancer

This invention relates to the fatty acid desaturase genes, designated SbDES2 and SbDES3, cloned from an expressed sequence tag (EST) database prepared from isolated root hairs from sorghum. Heterologous expression of the cDNAs inrevealed that recombinant SbDES2 converted palmitoleic acid (16:1&#x394;) to hexadecadienoic acid (16:2&#x394;), and that recombinant SbDES3 was capable of converting hexadecadienoic acid into hexadecatrienoic acid (16:3&#x394;). Desaturase enzymes capable of performing desaturation reactions producing a terminal double bond have not previously been characterized in a plant system.

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Resveratrol has been reported to have hypolipidemic properties. We investigated whether resveratrol and its analogs: pterostilbene, piceatannol and resveratrol trimethyl ether, would activate the peroxisome proliferator-activated receptor alpha (PPAR&#x3b1;) isoform. This nuclear receptor is proposed to mediate the activity of lipid-lowering drugs such as the fibrates. The four stilbenes and ciprofibrate (positive control) were evaluated for the activation of endogenous PPAR&#x3b1; in H4IIEC3 cells transfected with a luciferase gene reporter construct. Pterostilbene demonstrated the highest induction of PPAR&#x3b1;; the maximal response to pterostilbene was similar to that obtained with the hypolipidemic drug, ciprofibrate.

Pterostilbene as an agonist for the peroxisome proliferator-activated receptor alpha isoform

Resveratrol, a stilbenoid antioxidant found in grapes, wine, peanuts and other berries, has been reported to have hypolipidemic properties. Resveratrol and its three analogs (pterostilbene, piceatannol and resveratrol trimethyl ether) were evaluated for their effects on the activation of the peroxisome proliferator-activated receptor alpha (PPAR&#x3b1;) isoforms, a receptor shown to mediate the activity of lipid-lowering drugs such as the fibrates. The four stilbenes and ciprofibrate (positive control) were evaluated for the activation of endogenous PPAR&#x3b1; in H4IIEC3 cells. Pterostilbene demonstrated the highest induction of PPAR&#x3b1; demonstrating increases of 7- and 9-14 fold relative to control. The maximal responses to pterostilbene are similar to those obtained with the hypolipidemic drug, ciprofibrate; that is, pterostilbene acts as a PPAR&#x3b1; agonist, like that of the fibrate class, and is a more effective hypolipidemic agent than resveratrol.

This invention relates to an O-methyltransferase gene cloned from sorghum, the sorghum O-methyltransferase-3 gene, SbOMT3. Quantitative real-time RT-PCR and recombinant enzyme studies with putative O-methyltransferase sequences obtained from an EST data set from sorghum have led to the identification of the novel root hair-specific O-methyltransferase designated SbOMT3. Transgenic plants which express SbOMT3 can convert resveratrol into pterostilbene in planta. SbOMT3 is also involved in the biosynthesis of sorgoleone.

Growing community of inventors

Oxford, MS, United States of America

Agnes M Rimando