Effects Of Sodium Caprate Research Articles

Sodium caprate augments the hypoglycemic effect of berberine via AMPK in inhibiting hepatic gluconeogenesis

Berberine (BER), a natural product and active ingredient of genera Berberis and Coptis, has been demonstrated to possess anti-diabetic activities. However, the poor bioavailability of this agent greatly limits its clinical application. In our previous study, we demonstrated that co-administration of sodium caprate, an absorption enhancer, with BER could significantly increase the bioavailability of BER without any serious mucosal damage. Here, we investigated the effects of BER on AMP-activated protein kinase (AMPK)/gluconeogenesis pathway and the effects of sodium caprate on hypoglycemic action of BER. The ability of BER co-administered with sodium caprate to reduce insulin resistance was investigated in diabetic rat model induced by high-fat diet and low dose STZ. Western blot was performed to evaluate effects of BER on AMPK signaling proteins involved in hepatic gluconeogenesis in diabetic rat and HepG2 hepatocytes. BER reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in diabetic rats. Similarly, BER reduced plasma triglycerides and improved insulin action in diabetic rats. BER down-regulated the elevated expressions of gluconeogenesis key enzymes PEPCK and G6Pase, inhibited the translocation of TORC2 from cytoplasm to nucleus and increased AMPK activity in liver tissues. The effect of BER was higher when co-administered with sodium caprate. BER treatment resulted in reduced glucose production in HepG2 hepatocytes. BER increased AMPK activity, reduced the expression of PEPCK, and the nuclear transcription factors PGC-1, HNF-4α and FOXO1. The effect of BER on gluconeogenesis could be partly blocked by AMPK inhibitor, Compound C. BER could suppress hepatic gluconeogenesis in rat model of diabetes at least in part via stimulation of AMPK activity and this action of BER is augmented by sodium caprate.

β-Casein aids in the formation of a sodium caprate-induced β-lactoglobulin B gel

The effects of sodium caprate on the gelation of β-lactoglobulin B and a β-lactoglobulin B/β-casein mixture at ambient temperature were investigated using ultrasonic spectroscopy and rheology. A 12% β-lactoglobulin B solution gelled in the presence of 3.6% sodium caprate. Conversely, sodium caprate did not induce the formation of a gel when β-casein was in isolation, regardless of the protein concentration. Although a 6% β-lactoglobulin B/1.8% sodium caprate solution did not form a gel, a gel was formed when 6% β-casein was added to a mixture containing 6% β-lactoglobulin B and 3.6% sodium caprate. This gel showed comparable rheological properties to that of a gel containing 12% β-lactoglobulin B. The results clearly indicated that β-casein aids in the gelation of a β-lactoglobulin B/sodium caprate mixture, when the concentration of β-lactoglobulin B is insufficient to allow for gelation. It appears that β-casein self-aggregation is also inhibited. Therefore, it could be concluded that β-casein can be used as a texture modifier for β-lactoglobulin gelation induced by sodium caprate.

Characterization of β-Lactoglobulin A Gelation in the Presence of Sodium Caprate by Ultrasound Spectroscopy and Electron Microscopy

The effect of sodium caprate (a fatty acid salt) on the formation of beta-lactoglobulin A gels was studied at constant temperature (30 or 35 degrees C) using ultrasonic spectroscopy. During incubation at these temperatures, ultrasonic attenuation increased with the addition of sodium caprate, and reached a plateau after 5-7 h of incubation. Comparing beta-lactoglobulin A with and without sodium caprate, a decrease in net ultrasonic velocity was observed. These results suggested that aggregation occurred during incubation with sodium caprate, and the sample showed an increase in compressibility. Transmission electron microscopy with negative staining showed the formation of filamentous aggregates of beta-lactoglobulin A at around 3-4.5 h of incubation with sodium caprate. These results demonstrated that sodium caprate induced the formation of structures with unique gel properties compared to those formed by heating beta-lactoglobulin in the presence of NaCl alone.

Effect of sodium caprate on the intestinal absorption of two modified antisense oligonucleotides in pigs

Sodium caprate, a medium chain fatty acid, is known to enhance the transport of drugs across the intestinal mucosa in cell culture systems and small animal species. The aim of the present study was to evaluate the effect of this enhancer on the oral absorption of two chemically modified antisense oligonucleotides ISIS 2503 (phosphorothioate) and ISIS 104838 (methoxyethyl modified phosphorothioate) using an intra-intestinal catheterised pig model. Sodium caprate at doses 25, 50 and 100 mg/kg was effective in enhancing systemic delivery of both antisense chemistries. At all enhancer doses, the absorption of both chemistries was rapid ( T max 10 min) and short lived (plasma levels fell below detection by 2 h following administration). The pharmacokinetic parameters (AUC, C max, T max) of both chemistries were unchanged with the increase in the permeation enhancer dose. The oral bioavailability with methoxyethyl modified phosphorothioate (ISIS 104838) was higher relative to unmodified phosphorothioate. Sodium caprate was rapidly absorbed following intra-intestinal administration ( T max approximately 7 min regardless of the dose) and its pharmacokinetics were linear with dose. All tested formulations were well tolerated by the animals and no abnormal histopathological findings were observed following histological evaluation of intestinal tissues from pigs exposed to multi-dose administration of sodium caprate. It is concluded that sodium caprate can improve the oral delivery of antisense oligonucleotides in pigs and that its membrane-permeation effect is rapid, short-lived and dose independent.

Absorption-enhancing effects of sodium caprate and palmitoyl carnitine in rat and human colons.

We examined the enhancing action of sodium caprate and palmitoylcarnitine on the permeability of fluorescein isothiocyanate dextran 4000 as a paracellular permeant compound in isolated rat and human colon samples using the Ussing-type chamber method. In the absence of an enhancer, the permeation clearance of fluorescein isothiocyanate dextran 4000 was not significantly different in the rat and human colons, but the electric membrane resistance was smaller in the rat colon than in the human colon. Sodium caprate and palmitoylcarnitine increased permeation clearance and decreased electric membrane resistance in both types of colonic membrane, showing that the rat colon can be used as a model of the human colon for studies of enhancer effects. A calmodulin antagonist significantly inhibited the action of sodium caprate in both colonic membranes. However, it tended to promote the effects of palmitoylcarnitine on permeation clearance and electric membrane resistance. These results suggest that sodium caprate induces the contraction of the perijunctional actomyosin ring to widen the tight junction and that the mechanism of palmitoylcarnitine is different from that of sodium caprate in the human colon, as reported previously for Caco-2 cell monolayers.

Effect of Sodium Caprate on the Absorption of Progesterone from Mixed Suppositories Administered to the Vagina of Rabbits

The promoting effect of sodium caprate (CAP) added to a progesterone mixed suppository was investigated in vitro and in vivo. The mixed suppository (S50), consisting of Witepsol W35 and ethylene-vinyl acetate copolymers (EVA40Y and EVA250); and a control suppository of Witepsol W35 (C50) were prepared by the fusion method. One or five percent of CAP was added to S50 and C50 containing 50 mg of progesterone. The release of progesterone from C50 was not influenced by the addition of CAP and there was no change in plasma level profile of progesterone after administration to the vagina of rabbits. On the other hand, S50 added with CAP showed rapid elevation of the plasma level of progesterone without any change in the sustained-release characteristics.

Enhancement of colonic drug absorption by the transcellular permeation route.

The effects of sodium caprate and sodium caprylate on transcellular permeation routes were examined in rats. The release of membrane phospholipids was significantly increased only by caprate, while protein release did not change from the control in the presence of caprate or caprylate, indicating that the extent of membrane disruption was insufficient to account for enhanced permeation. Using brush border membrane (BBM) vesicles prepared from colon, with their protein and lipid component labeled by fluorescent probes, the perturbing actions of caprate and caprylate toward the membrane were examined by fluorescence polarization. Caprate interacted with membrane protein and lipids, and caprylate mainly with protein, causing perturbation to the membrane. The release of 5(6)-carboxyfluorescein previously included in BBM vesicles was increased by caprate but not by caprylate. These results suggest that caprate enhances permeability via the transcellular route through membrane perturbation.