Printable-Microencapsulated Ascorbic Acid for Personalized Topical Delivery.

This study presents the successful development of printable-microencapsulated ascorbic acid (AA) for personalized topical delivery using laser printing technology. Rice flour with a 10% AA content was selected as an encapsulation material. Hydrophobic nanosilica was used to create negative electrostatic charges on the microencapsulated surfaces via a high-speed mixture. This process facilitated the microencapsulated AA fabrication using a commercial laser printer and produced a well-patterned design with some minor print defects, such as banding and scattering. The amount of encapsulated AA per area was 0.28 mg/cm2, and the RGB color code was 0,0,0. An emulsion carrier system comprising pentylene glycol (P5G) or diethylene glycol monoethyl ether (DEGEE), Tween 20, oleic acid, and deionized (DI) water at a ratio of 20:30:30:20 was developed to enhance AA transmission into the skin. The Franz diffusion cell technique was used to investigate topical absorption on Strat-M membranes using P5G and DEGEE as enhancers. The steady-state fluxes were 8.40 (±0.64) and 10.04 (±0.58) µg/h/cm2 for P5G and DEGEE, respectively. Cytotoxicity tests conducted on fibroblast cells revealed low cytotoxicity for the encapsulation products and carriers.

Isolation of Intrapulmonary Artery and Smooth Muscle Cells to Investigate Vascular Responses.

The intrapulmonary artery (IPA) and vascular smooth muscle cells (VSMCs) isolated from rat lungs can be used to study the underlying mechanisms of vasoconstriction and vasorelaxation. After isolating the IPA and VSMCs, the characteristics of vascular responses in physiological and pathological conditions can be assessed in the absence of extrinsic factors such as nerve signals, hormones, cytokines, etc. Thus, the IPA and VSMCs serve as excellent models for studying vascular physiology/pathophysiology, along with various experimental investigations, such as modulation by pharmacological agents, patch-clamp electrophysiological analysis, calcium imaging, etc. Here, we have used a technique for isolating the IPA to investigate vascular responses in an organ bath setup. IPA segments were mounted on the organ bath chamber via intraluminal wires and stimulated by various pharmacological agents. The changes in IPA vascular tone (i.e., vasoconstriction and vasorelaxation), were recorded using an isometric force transducer and physiological data analysis software program. We implemented several experimental protocols, which can be adapted to investigate the mechanisms of vasorelaxation/vasoconstriction for studying the pharmacological activities of phytochemical or synthetic drugs. The protocols can also be used to evaluate drugs' roles in modulating various diseases, including pulmonary arterial hypertension. The IPA model allows us to investigate the concentration-response curve, which is crucial in assessing drugs' pharmacodynamic parameters.

Safety assessment on comedogenicity of dermatological products containing d-alpha tocopheryl acetate in Asian subjects: A double-blind randomized controlled trial.

A double-blind randomized controlled trial was used to assess the comedogenic potential of the dermatological products containing d-Alpha tocopheryl acetate. A total of 15 healthy males (20-45 years old) with prominent follicular orifices and the ability to form comedones on the upper aspect of the back were enrolled. Each participant was given pads containing 4 test products. The positive control arm received a pad containing octyl palmitate which is a reported comedogenic material. The negative control arm received a pad without any test material. Participants were randomized to apply either the positive, negative or the active test cream to the application area for 4 weeks. Comedones were identified using epidermal biopsy under a stereomicroscope. The average number of microcomedone before exposure (baseline) with octyl palmitate was 6.1 ± 0.6 (mean ± SEM), and changed to 27.3 ± 4.7 which was more than 50% increase in comedone formation in every subject with the average change from base line was 365.4 ± 87.6%. In the negative control arm the average number of microcomedone at baseline was 6.4 ± 1.1 and at 4 week-application was 3.4 ± 0.6 (-43.0 ± 9.5% increased). All tested products produced less than a 50% increase in the number of microcomedones. Analyzed data from 12 subjects indicated non-comedogenic potential of the tested products containing-alpha tocopheryl acetate and other ingredients including lanolin, kernel oil and avocado oil and sunflower oil, etc. The octyl palmitate produced more than 50% increase in comedone formation in every analyzed subject.

Extract of Aquilaria crassna leaves and mangiferin are vasodilators while showing no cytotoxicity.

The leaves of Aquilaria spp. promote "physiological balance", and are "cardiotonic and provide blood nourishment". In Asia, these leaves are increasingly consumed as tea and claimed to provide benefits to cardiovascular function, albeit without any scientific proof. Therefore, this study sought to evaluate the action of Aquilaria crassna leaf aqueous extract (AE) on vascular function and vascular smooth muscle cytotoxicity. AE and a main constituent, mangiferin were investigated for their vasorelaxation of rat mesenteric arteries and aortae in vitro. Acute cytotoxicity of AE (0.1-1000 µg/ml) and mangiferin (0.1-100 µM) on rat enzymatically isolated vascular smooth muscle cells was assayed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. AE dilated rat mesenteric arteries (EC50∼107 µg/ml, Emax∼95%) more than aorta (EC50∼265 µg/ml, Emax∼76%, p < 0.05). AE-induced vasodilation in mesenteric artery was reduced by endothelial removal (EC50∼202 µg/ml, p < 0.05), incubation with endothelial nitric oxide synthase (eNOS) (100 µM, L-NAME) (EC50∼309 µg/ml, p < 0.05), and partly reduced by L-type Ca2+ channel blockade at higher concentrations. Likewise, mangiferin (1-100 µM) dilated the mesenteric artery more potently than the aorta. However, its maximum relaxation was less than with AE (41% in the mesenteric artery and <10% in the aorta). Isolated vascular smooth muscle cells incubated in AE or mangiferin for 1 h showed no cytotoxicity. Thus, AE is a vasorelaxant while being free of acute cytotoxicity towards vascular smooth muscle, thus potentially ameliorating human vascular dysfunction.

Eulophia macrobulbon extract relaxes rat isolated pulmonary artery and protects against monocrotaline-induced pulmonary arterial hypertension.

BACKGROUND: Extract of the wild orchid, Eulophia macrobulbon (EM) inhibits phosphodiesterase5 (PDE5) suggesting it could preferentially dilate the pulmonary vasculature. PURPOSE AND STUDY DESIGN: To pharmacologically characterize the vascular actions of EM ethanolic extract and its active compound, 1-(4'-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol using isolated pulmonary arteries (PA) from rats having pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). PA were fixed and prepared for histology. RESULTS: EM extract relaxed PA (EC50 = 0.17  mg/ml, Emax ∼ 94%) but less so for aorta (EC50 = 0.51 mg/ml, Emax ∼ 62%), suggesting some selectivity towards the pulmonary circulation. PA vasorelaxation was reduced by endothelial removal or NG-nitro-L-arginine methyl ester, but unaffected by indomethacin, apamin +charybdotoxin, 4-aminopyridine, glibenclamide, iberiotoxin, or 1H - [1,2,4]oxadiazolo[4,3-a]quinoxalin -1- one. Sodium nitroprusside-induced relaxation was enhanced by EM extract, probably via PDE5 inhibition. EM extract reduced contractions evoked by extracellular Ca2+application, and inhibited intracellular Ca2+release activated by phenylephrine. The phenanthrene relaxed PA independently of the endothelium. MCT thickened walls and decreased lumens of PA, and hypertrophied right ventricular myocytes, effects ameliorated by 3 weeks of oral sildenafil (20  mg/kg) or EM extract (15, 450 or 1000  mg/kg). CONCLUSION: PAH is improved by EM extract acting through PA relaxation mediated through endothelial NO, reduced Ca2+-mobilization, and reduced PA wall thickness and right ventricular hypertrophy.

Vasorelaxant and Hypotensive Effects of an Ethanolic Extract of Eulophia macrobulbon and Its Main Compound 1-(4'-Hydroxybenzyl)-4,8-Dimethoxyphenanthrene-2,7-Diol.

Background: Ethnopharmacological studies demonstrated the potential for Eulophia species to treat inflammation, cancer, and cardio-metabolic diseases. The aim of the study was to investigate the vasorelaxant effect of ethanolic Eulophia macrobulbon (EM) extract and its main phenanthrene on rat isolated mesenteric artery and to investigate the hypotensive effect of EM. Methods: The vasorelaxant effects of EM extract or phenanthrene and the underlying mechanisms were evaluated on second-order mesenteric arteries from Sprague Dawley rats. In addition, the acute hypotensive effect was evaluated in anesthetized rats infused with cumulative concentrations of the EM extract. Results: Both EM extract (10-4-1 mg/ml) and phenanthrene (10-7-10-4 M) relaxed endothelium-intact arteries, an effect that was partly reduced by endothelium removal (p < 0.001). A significant decrease in the relaxant effect of the extract and the phenanthrene was observed with L-NAME and apamin/charybdotoxin in endothelium-intact vessels, and with iberiotoxin in denuded vessels. SNP (sodium nitroprusside)-induced relaxation was significantly enhanced by EM extract and phenanthrene. By contrast, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one), 4-aminopyridine and glibenclamide (endothelium-denuded vessels) and indomethacin (endothelium-intact vessels) had no effect. In calcium-free solution, both the EM extract and phenanthrene inhibited extracellular Ca2+-induced contraction in high KCl and phenylephrine (PE) pre-contracted rings. They also inhibited the intracellular Ca2+ release sensitive to PE. The acute infusion of EM extract (20 and 70 mg/kg) induced an immediate and transient dose-dependent hypotensive effect. Conclusion: The ethanolic extract of EM tubers and its main active compound, 1-(4'-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (phenanthrene) induced vasorelaxant effects on rat resistance vessels, through pleiotropic effects including endothelium-dependent effects (NOS activation, enhanced EDH production) and endothelium-independent effects (opening of KCa channels, inhibition of Ca2+ channels, inhibition of intracellular Ca2+ release and PDE inhibition).