betadex and pterostilbene

The present investigation was designed to explore the effectiveness of pterostilbene (PT) on insulin resistance, metabolic syndrome and oxidative stress in fructose-fed insulin resistant rats.. Age-matched, male Sprague-Dawley rats (330±30g body weight) were allocated into five groups (n=10). Control (C) group received 65% cornstarch, and the diabetic (D) group received 65% fructose for eight weeks. The third group (D+PT20) received 65% fructose and PT 20mg/kg/day for eight weeks. The fourth group (D+PT40) received 65% fructose and PT 40mg/kg/day for eight weeks. The fifth group (D+M) received 65% fructose and metformin (M) 100mg/kg/day for eight weeks. PT was dissolved in 10% β-cyclodextrin and given orally to rats. Several biochemical parameters were determined to assess the PT efficacy against insulin resistance, metabolic complications, and hepatic oxidative stress.. Significantly high HOMA-IR (p<0.001) values in D group compared to C group indicate the presence of insulin resistance. Significantly high levels of TBARS (p<0.001) and decreased levels of SOD (p<0.001) and GSH (p<0.001) in hepatic tissues of D group indicate oxidative stress associated with insulin resistance. Pterostilbene treatment to fructose-fed diabetic rats significantly decreased HOMA-IR (p<0.001) values. Furthermore, PT treatment significantly decreased hepatic TBARS (p<0.001) and increased SOD (p<0.001) and GSH (p<0.001) levels in fructose-fed diabetic rats.. Current study reveals that PT is successful in ameliorating glycemic control, insulin sensitivity while diminishing metabolic disturbances and hepatic oxidative stress in a fructose-induced T2DM rat model.

Topics: Animals; beta-Cyclodextrins; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Fructose; Insulin Resistance; Male; Metabolic Syndrome; Metformin; Oxidative Stress; Rats; Rats, Sprague-Dawley; Stilbenes; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene, PTS) possesses various health-promoting effects. This study aimed to investigate the impacts of aqueous solubility, fasting, dose escalation, and dosing route on its bioavailability in Sprague-Dawley rats.. Upon intravenous administration (2.5 mg/kg), PTS had rapid clearance (Cl = 68.2 ± 9.8 mL/min/kg) and moderate terminal elimination half-life (t(1/2λz) = 93.9 ± 22.3 min). Dose-escalation led to about twofold decline in clearance at the dose of 25 mg/kg (Cl = 36.4±7.8 mL/min/kg). When given in oral suspension (15 mg/kg), PTS had relatively low bioavailability (F = 15.9 ± 7.8%) while fasting substantially attenuated its bioavailability (F< 5.5 %). However, when dosed in a solution formulated with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) (15 mg/kg), PTS possessed good bioavailability (F = 59.2 ± 19.6%). Dose escalation resulted in about twofold increase in bioavailability at the dose of 60 mg/kg. Sublingual delivery (2.5 mg/kg) led to rapid absorption and moderate bioavailability (F = 25.8 ± 13.1%). Statistical comparison clearly indicated that the pharmacokinetics of PTS was more favorable than resveratrol.. Aqueous solubility was identified as a barrier to its oral bioavailability while solubilizing PTS with HP-β-CD substantially increased its bioavailability; dose manipulation was a practical strategy to enhance its bioavailability and systemic exposure; and its delivery through oral mucosa was feasible. As PTS possessed superior pharmacokinetics, it is a favorable candidate for further development.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Intravenous; Administration, Oral; Administration, Sublingual; Animals; beta-Cyclodextrins; Biological Availability; Dose-Response Relationship, Drug; Fasting; Male; Rats; Rats, Sprague-Dawley; Solubility; Stilbenes

In this work, a reversed phase high performance liquid chromatography (RP-HPLC) method was developed for the determination of pterostilbene in food samples. The novel method is based on the addition of cyclodextrins (CDs) to the mobile phase where the complexation of pterostilbene by CDs is carried out. In order to select the most suitable conditions for the RP-HPLC method, the effect of several physico-chemical parameters on the complexation of pterostilbene by CDs was studied. Our results show that the addition of 12 mM HP-β-CD to a 50:50 (v/v) methanol:water mobile phase at 25°C and pH 7.0 significantly improves the main analytical parameters. In addition, it was seen that pterostilbene forms a 1:1 complex with HP-β-CD, showing an apparent complexation constant of 251±13 M(-1). Finally, in order to study the validity of the proposed method, blueberries were analyzed and the concentration of pterostilbene has been determined.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Blueberry Plants; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Hydrogen-Ion Concentration; Linear Models; Plant Extracts; Reproducibility of Results; Sensitivity and Specificity; Stilbenes; Temperature; Water