Insights into the formulation properties, biocompatibility, and permeability of poorly water-soluble methoxyflavones with PEG400 and propylene glycol

Herein, thermal and non-thermal techniques were used to elucidate the putative physical and chemical interactions between poorly water-soluble Kaempferia methoxyflavones and PEG400/propylene glycol. Additionally, the biocompatibility of methoxyflavone-glycol solutions was evaluated using Caco-2 cells whereas the absorptive transport was investigated by measuring the apparent permeability coefficient (Papp) of the methoxyflavones and transepithelial electrical resistance (TEER) of the Caco-2 cell monolayer. Data from differential scanning calorimetry, Fourier-transform infrared (FTIR), and proton nuclear magnetic resonance (1H-NMR) spectroscopic analysis revealed physicochemical compatibility between the three methoxyflavones and PEG400/propylene glycol. Furthermore, PEG400 and propylene glycol solutions of the methoxyflavones were shown to be compatible with Caco-2 cells at pharmacologically effective concentrations. In vitro transport studies across the Caco-2 cell monolayer revealed high Papp values of 24.07 × 10–6 to 19.63 × 10–6 cm s–1 for PEG400 solutions of the methoxyflavones. The TEER values of the Caco-2 cell monolayers indicated that the increased drug transport was partly due to increased tight junction openings, but without compromising the epithelial barrier integrity. The good pharmaceutical and biocompatibility profiles, as well as improved transport of the methoxyflavones in PEG400 and propylene glycol solutions, are suggestive of the worthiness of this approach for further consideration pertaining to the development of these drugs into oral liquid dosage forms

Cardiovascular effects of Tacca integrifolia Ker-Gawl. extract in rats

Rhizome of Tacca integrifolia, a Thai folk medicinal herb, has been used for controlling blood pressure and improving sexual function in humans. However, the biological activities of this herb on the cardiovascular system have not yet been documented. In the present study, we investigated the cardiovascular effects of methanolic extract from the rhizome of this herb (Tacca extract). In the in vivo study, intravenous injection of the Tacca extract (0.04-40 mg/kg) caused a decrease in both mean arterial blood pressure and heart rate of anesthetized rats (Nembutal sodium, 60 mg/kg, i.p.) in a dose dependent manner. Pretreatment of the animals with muscarinic receptor antagonist, atropine (1 mg/kg, i.v.), significantly reduced the hypotensive and the negative chronotropic activities of the Tacca extract. In the in vitro preparation, the Tacca extract (0.001-3 mg/ml) caused a decrease in both force and rate of spontaneous contraction of isolated atria in a dose dependent manner. These effects were reduced by preincubation of the atria with atropine (10-7 or 10-6 M). For isolated blood vessels, the Tacca extract (0.003-3 mg/ ml) caused vasodilation of endothelium-intact thoracic aortic rings pre-constricted with phenylephrine (3× 10-6 M). This effect disappeared after pre-incubation of blood vessels with atropine (10-6 M) or with Nω-nitro- L-arginine (3×10-4 M), or by removing the vascular endothelium. The results obtained suggest that the hypotensive and negative chronotropic effects of the Tacca extract in the rat are due to the active components acting via the muscarinic receptors at the blood vessel to cause vasodilatation by stimulating the release of nitric oxide, as well as on the muscarinic receptors at the atria to cause the decrease of both rate and force of the atrial contraction

Improved dissolution of Kaempferia parviflora extract for oral administration by preparing solid dispersion via solvent evaporation

Kaempferia parviflora, a plant in the family Zingiberaceae, has been used in Thai traditional medicines for treating hypertension and promoting longevity with good health and well-being. However, its limited aqueous solubility and low dissolution restrict its bioavailability. The aim of the study was therefore to improve the dissolution rate of K. parviflora extracted with dichloromethane (KPD) by solid dispersions. Different water-soluble polymers were applied to improve dissolution of KPD. The solid dispersions in different ratios were prepared by solvent evaporation method. Only hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol-polyethylene glycol grafted copolymer (PVA-co-PEG) could be used to produce homogeneous, powdered solid dispersions. Physical characterization by scanning electron microscopy, hot stage microscopy, differential scanning calorimetry and powder X-ray diffractometry, in comparison with corresponding physical mixtures, showed the changes in solid state during the formation of solid dispersions. Dissolution of a selected marker, 5,7,4′-trimethoxyflavone (TMF), from KPD/HPMC and KPD/PVA-co-PEG solid dispersions was significantly improved, compared with pure KPD. The dissolution enhancement by solid dispersion was influenced by both type and content of polymers. The stability of KPD/HPMC and KPD/PVA-co-PEG solid dispersions was also good after 6-month storage in both long-term and accelerated conditions. These results identified that the KPD/HPMC and KPD/PVA-co-PEG solid dispersions were an effective new approach for pharmaceutical application of K. parviflora

Cardiovascular effects of an n-butanol extract from fresh fruits of Randia siamensis

Randia siamensis is used in Thai folkloric medicine for inducing abortion and controlling blood pressure. The present study investigated the cardiovascular effects of an R. siamensis fruit extract, and mechanisms involved in anesthetized normal and reserpinized rats. R. siamensis (0.4-12 mg/kg) i.v. increased the mean arterial pressure (MAP) and heart rate. Both effects were significantly inhibited by phentolamine (2 mg/kg, i.v.) or propranolol (0.6 mg/kg, i.v.). The combination of phentolamine and propranolol, or reserpine pretreatment, inhibited the positive chronotropic effect with a slight decrease in the MAP. In vitro, R. siamensis (0.001-0.3 mg/ml) increased the rate of beating of the right atrium and the strength of the electrical field-stimulated contraction of the left atrium, both effects were inhibited by propranolol, or with reserpine pretreated rats. R. siamensis (0.01-3 mg/ml) produced a contraction of isolated thoracic aorta, which was potentiated by N-G-nitro-L-arginine (LNA), or by removal of the vascular endothelium, but inhibited by phentolamine, or reserpine. R. siamensis (0.3-3 mg/ml) caused a relaxation of phenylephrine-preconstricted aortic rings, which was potentiated with reserpine pretreatment, and abolished after removal of the vascular endothelium, or in the presence of LNA. These results suggest that R. siamensis extract exerts both hypertensive and positive chronotropic effects via the alpha-- and beta-adrenergic receptors of blood vessels and the heart, due to release of endogenous catecholamines, likely from nerve ending and adrenal medulla. The hypotensive activity results from the release of nitric oxide causing dilatation of the blood vessels. The present data support the folkloric therapeutic uses of this plant

Decreased body-fat accumulation and increased vasorelaxation to glyceryl trinitrate in middle-aged male rats following six-weeks consumption of coconut milk protein

We investigated whether coconut milk protein (CMP) contributes to the beneficial effects of coconut milk consumption on cardiovascular health markers previously found in middle-aged rats. CMP was isolated and precipitated from dried fresh coconut milk, then gavaged (1 g/kg) to middle-aged male rats for six weeks; control rats received distilled water. Compared to controls, CMP caused decreased body fat and lipid accumulation in liver cells and the platelet count. CMP did not affect basal blood pressure or heart rate in anesthetized rats. Vascular responsiveness to phenylephrine, DL-propargylglycine (PAG), acetylcholine or sodium nitroprusside was unaffected, but vasorelaxation to glyceryl trinitrate (GTN) increased. Effects of ODQ on vasorelaxation to GTN were similar in both groups. Expression of blood vessel eNOS, CSE and sGC was normal. The cyclic guanosine monophosphate (cGMP) level of CMP-treated rats was normal but addition of GTN increased cGMP and NO concentration more in CMP-treated rats than in controls, an effect unaltered by addition of diadzin. Taken together, CMP appears partially responsible for the improvement in cardiovascular health markers caused by coconut milk in middle-aged male rats

Decreased body-fat accumulation and increased vasorelaxation to glyceryl trinitrate in middle-aged male rats following six-weeks consumption of coconut milk protein

Abstract We investigated whether coconut milk protein (CMP) contributes to the beneficial effects of coconut milk consumption on cardiovascular health markers previously found in middle-aged rats. CMP was isolated and precipitated from dried fresh coconut milk, then gavaged (1 g/kg) to middle-aged male rats for six weeks; control rats received distilled water. Compared to controls, CMP caused decreased body fat and lipid accumulation in liver cells and the platelet count. CMP did not affect basal blood pressure or heart rate in anesthetized rats. Vascular responsiveness to phenylephrine, DL-propargylglycine (PAG), acetylcholine or sodium nitroprusside was unaffected, but vasorelaxation to glyceryl trinitrate (GTN) increased. Effects of ODQ on vasorelaxation to GTN were similar in both groups. Expression of blood vessel eNOS, CSE and sGC was normal. The cyclic guanosine monophosphate (cGMP) level of CMP-treated rats was normal but addition of GTN increased cGMP and NO concentration more in CMP-treated rats than in controls, an effect unaltered by addition of diadzin. Taken together, CMP appears partially responsible for the improvement in cardiovascular health markers caused by coconut milk in middle-aged male rats