Agnes M. Rimando - Oxford MS, US Dennis R. Feller - Oxford MS, US Wallace H. Yokoyama - Berekley CA, US
Assignee:
The United States of America as represented by the Secretary of Agriculture - Washington DC The University of Mississippi - University MS
International Classification:
A61K 31/075 A61K 38/00 A01N 65/00
US Classification:
514720, 514 74, 424732
Abstract:
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 (PPARα) 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 PPARα in H4IIEC3 cells. Pterostilbene demonstrated the highest induction of PPARα 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 PPARα agonist, like that of the fibrate class, and is a more effective hypolipidemic agent than resveratrol.
Pterostilbene As An Agonist For The Peroxisome Proliferator-Activated Receptor Alpha Isoform
Agnes M. Rimando - Oxford MS, US Dennis R. Feller - Oxford MS, US Wallace H. Yokoyama - Berekley CA, US
Assignee:
The United States of America, as represented by the Secretary of Agriculture - Washington DC The University of Mississippi - University MS
International Classification:
A61K 31/075 A61K 38/00 A01N 65/00
US Classification:
514720, 514 74, 424732
Abstract:
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 (PPARα) 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 PPARα in H4IIEC3 cells transfected with a luciferase gene reporter construct. Pterostilbene demonstrated the highest induction of PPARα; the maximal response to pterostilbene was similar to that obtained with the hypolipidemic drug, ciprofibrate.
Zhiqiang Pan - Oxford MS, US Agnes M. Rimando - Oxford MS, US Scott R. Baerson - Oxford MS, US
Assignee:
The United States of America, as represented by the Secretary of Agriculture - Washington DC
International Classification:
A01H 5/00 C12N 15/82 C07H 21/04
US Classification:
800298, 800281, 435419, 536 232
Abstract:
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 in revealed that recombinant SbDES2 converted palmitoleic acid (16:1Δ) to hexadecadienoic acid (16:2Δ), and that recombinant SbDES3 was capable of converting hexadecadienoic acid into hexadecatrienoic acid (16:3Δ). Desaturase enzymes capable of performing desaturation reactions producing a terminal double bond have not previously been characterized in a plant system.
Agnes Rimando - Oxford MS, US Dennis Feller - Oxford MS, US Wallace Yokoyama - Berekley CA, US
International Classification:
A61K 36/45 A61K 36/87 A61K 31/704
US Classification:
424732000, 424766000, 514025000
Abstract:
Resveratrol, a stilbenoid antioxidant found in grapes, wine, peanuts and other berries, has been reported to have hypolipidemic properties. We investigated whether resveratrol and its three analogs (pterostilbene, piceatannol and resveratrol trimethyl ether) would activate the peroxisome proliferator-activated receptor alpha (PPARα) isoform. This nuclear receptor is proposed to mediate the activity of lipid-lowering drugs such as the fibrates. The four stilbenes were evaluated along with ciprofibrate (positive control) at 1, 10, 100, 300 μM concentrations, for the activation of endogenous PPARα in H4IIEC3 cells. Cells were transfected with a peroxisome proliferator response element-AB (rat fatty acyl CoA β-oxidase response element)—luciferase gene reporter construct. Of the four analogs, pterostilbene demonstrated the highest induction of PPARα showing 7- and 9-14 fold increases in luciferase activity at 100 and 300 μM, respectively, relative to control. The maximal luciferase activity responses to pterostilbene at 100 μM are similar to those obtained with the hypolipidemic drug, ciprofibrate. These results suggest that pterostilbene acts as a PPARα agonist, like that of the fibrate class, and may be a more effective hypolipidemic agent than resveratrol.
Method To Ameliorate Oxidative Stress And Improve Working Memory Via Pterostilbene Administration
James A. Joseph - Plymouth MA, US Agnes M. Rimando - Oxford MS, US
Assignee:
The United States of America, as represented by th e Secretary of Agriculture - Washington DC
International Classification:
A61K 31/09 A61P 25/00
US Classification:
514719
Abstract:
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.
Two Novel Alkylresorcinol Synthase Genes From Sorghum; Cloning, Expression, Transformation And Characterization
Scott R. Baerson - Oxford MS, US Zhiqiang Pan - Oxford MS, US Agnes M. Rimando - Oxford MS, US Franck E. Dayan - Oxford MS, US Daniel Cook - Providence UT, US
Sorghum is considered to be an allelopathic crop species, producing phytotoxins such as the lipid benzoquinone sorgoleone (2-hydroxy-5-methoxy-3-[(Z,Z)-8′,11′,14′-pentadecatriene]-p-benzoquinone) which likely accounts for much of its allelopathic properties. Prior investigations into the biosynthesis of sorgoleone have 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. Current evidence suggests that sorgoleone biosynthesis occurs exclusively in root hair cells, involving the synthesis of a 5-pentadecatrienyl resorcinol intermediate derived from an unusual 16:3 fatty acyl-CoA starter unit. To characterize the enzymes responsible for the biosynthesis of this alkylresorcinol intermediate, a previously-described expressed sequence tag (EST) database prepared from isolated root hairs was first mined for all PKS-like sequences. Quantitative real-time RT-PCR analyses revealed that two of these sequences were preferentially expressed in root hairs, and recombinant enzyme studies demonstrated that both sequences (designated ARS1 and ARS2) encode ARS enzymes capable of accepting a variety of fatty acyl-CoA starter units. Furthermore, 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 are likely to participate in the biosynthesis of sorgoleone in planta. The sequences of ARS1 and ARS2 were also used to identify several rice genes encoding ARSs, which are likely involved in the production of defense-related alkylresorcinols.
Method To Ameliorate Oxidative Stress And Improve Working Memory Via Pterostilbene Administration
James A. Joseph - Plymouth MA, US Agnes M. Rimando - Oxford MS, US
Assignee:
The United States of America as represented by the Secretary of Agriculture - Washington DC
International Classification:
A61K 31/065 A61P 25/00
US Classification:
514733
Abstract:
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.
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