Abstract 617: Impact Of Pterostilbene On Blood Pressure and Other Metabolic Parameters In Adults

Objective: Pterostilbene is a polyphenol that is chemically related to resveratrol and commonly found in berries, such as blueberries. The purpose of this trial was to evaluate the effect of pterostilbene on metabolic parameters. METHODS: The trial was a prospective, randomized, double-blind, placebo-controlled study of patients with a total cholesterol ≥200 mg/dL and/or LDL ≥100 mg/dL. Patients were included if they were ≥18 years old and on either no cholesterol therapy or cholesterol medication at a stable dose for at least 2 months prior to baseline laboratory. Patients were excluded if they had significant hepatic, renal or GI tract disease or current overt cardiovascular disease; were receiving thiazolidinediones or fibric acids; were women who were pregnant or of reproductive potential. Eighty subjects were divided equally into one of four groups: (1) pterostilbene 125 mg twice daily; (2) pterostilbene 50 mg twice daily; (3) pterostilbene 50 mg + grape extract (GE) 100 mg twice daily; (4) matching placebo twice daily for 6-8 weeks. Patients received identical counseling on lifestyle intervention. Metabolic endpoints included blood pressure, body weight, and lipids. Linear mixed models were used to examine changes in metabolic parameters over time within treatment groups and compare changes over time across groups. Models were adjusted for age, sex and race. Results: The majority of patients completed the study (73/80; 91%). The average age was 54 years. The majority of patients were female (57/80; 71%), Caucasian (56/80; 70%), and had HTN (44/80; 55%). Both systolic (-7.8 mmHg; p<0.01) and diastolic blood pressure (-7.3 mmHg; p<0.001) were reduced with high dose pterostilbene. The only change in lipids was an increase in LDL with pterostilbene monotherapy (24.9 mg/dL; p<0.001) which was not seen with GE combination (p=0.47). Presence of a baseline cholesterol medication appeared to attenuate LDL effects. Patients not on cholesterol medication (n=51) exhibited minor weight loss with pterostilbene (-0.59 kg/m2; p=0.014). Conclusion: Pterostilbene reduces blood pressure in adults. Future studies should evaluate high dose pterostilbene with GE in a hypertensive population. Clinicaltrials.gov identifier NCT 01267227.

Co-induction of methyltransferase Rv0560c by naphthoquinones and fibric acids suggests attenuation of isoprenoid quinone action inMycobacterium tuberculosis

The superoxide generator menadione was previously demonstrated as an inducer of growth stage dependent protein patterns in Mycobacterium tuberculosis. The present study refines this observation by characterizing a novel 27-kDa protein that had not been observed in previous studies relying on younger cultures. A very similar response, based on two-dimensional gel electrophoretic analyses, was induced by the closely related naphthoquinone plumbagin. The 27-kDa protein was also induced by the pro-oxidant peroxisome proliferator gemfibrozil and to a lesser extent by the structurally related compounds fenofibrate and clofibrate. N-terminal sequence data of proteolytic fragments from the 27-kDa protein demonstrated its identity with protein Rv0560c, previously demonstrated to be inducible by salicylate, which also possesses peroxisome proliferating properties. Protein Rv0560c bears three conserved motifs characteristic of S-adenosylmethionine-dependent methyltransferases. Further sequence similarities suggest a function in the bio syn thesis of isoprenoid compounds, e.g., tocopherol, ubiquinone, and sterols. Such involvement is supported by the recognized yet unexplained widespread interference of menadione, salicylate, and fibrates with the isoprenoid quinones ubiquinone, menaquinone, and vitamin K. Induction of Rv0560c by fibrates, salicylate, and naphthoquinones is thus suggested to be caused by action on the plasma membrane, reminiscent of cytochrome P450BM-3 induction by fibrates in Bacillus megaterium, which catalyzes the hydroxylation of fatty acids and thus modulates membrane properties.Key words: peroxisome proliferators, membrane derangement, menaquinone antagonism, respiratory inhibition.