Modulation of non-steroidal anti-inflammatory drug-induced, ER stress-mediated apoptosis in Caco-2 cells by different polyphenolic antioxidants: a mechanistic study.

Objectives: Direct scavenging of reactive oxygen species could not prevent ER stress-associated cytotoxicity of indomethacin or diclofenac in Caco-2 cells. This study investigated the effects of three polyphenolic antioxidants epigallocatechin gallate (EGCG), phyllanthin and hypophyllathin in non-steroidal anti-inflammatory drug-induced Caco-2 apoptosis.

Methods: Cells were treated with ER stressors (indomethacin, diclofenac, tunicamycin or thapsigargin) and the polyphenols for up to 72 h.

Natural polyphenols prevent indomethacin-induced and diclofenac-induced Caco-2 cell death by reducing endoplasmic reticulum stress regardless of their direct reactive oxygen species scavenging capacity.

Objectives: Indomethacin (INDO) and diclofenac (DIC) can induce intestinal cell death through induction of oxidative stress-mediated ER stress and mitochondrial dysfunction. This study investigated the cytoprotective potential of 11 polyphenols, namely caffeic acid (CAF), curcumin (CUR), epigallocatechin gallate (EGCG), gallic acid (GAL), hypophyllanthin (HYPO), naringenin (NAR), phyllanthin (PHY), piperine (PIP), quercetin (QUE), rutin (RUT) and silymarin (SLY) against these two NSAIDs in Caco-2 cells.

Methods: Reactive oxygen species (ROS) production was determined with fluorescence spectroscopy using specific probes (DHE, DCFH-DA, HPF).

Rhinacanthin-C Mediated Herb-Drug Interactions with Drug Transporters and Phase I Drug-Metabolizing Enzymes.

Rhinacanthin-C is a major active constituent in (L.) Kurz, a plant widely used in herbal remedies. Its potential for pharmacokinetic herb-drug interaction may exist with drug transporters and drug metabolizing enzymes.

Flavonoids kaempferide and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone inhibit mitotic clonal expansion and induce apoptosis during the early phase of adipogenesis in 3T3-L1 cells.

Objective: Kaempferide and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (DTMC) are two major flavonoids found in Chromolaena odorata Linn. leaf extract. The aim of this study was to elucidate the mechanism by which these two flavonoids exerted their effect on adipogenesis.

Anti-adipogenic effect of flavonoids from Chromolaena odorata leaves in 3T3-L1 adipocytes.

Objective: The leaves of Chromolaena odorata, a highly invasive shrub found growing wild worldwide, are traditionally used for wound healing. Due to its high flavonoid contents, we aimed to find a new application for this plant. Preliminary tests using its ethanolic leaf extract showed that it could suppress the accumulation of lipids in adipocytes.

Potential P-glycoprotein-mediated herb-drug interaction of phyllanthin at the intestinal absorptive barrier.

Objectives: This study investigated the absorptive potential of phyllanthin across the polarized Caco-2 monolayers and the potential role of phyllanthin in P-glycoprotein (P-gp)-mediated drug interaction.

Methods: The absorptive potential of phyllanthin was predicted from its apparent permeability (P ) across the Caco-2 monolayers under the pH gradient condition (pH 6.5 -7.

Effects of rhinacanthin-C on function and expression of drug efflux transporters in Caco-2 cells.

Rhinacanthin-C is a bioactive naphthoquinone ester found in Rhinacanthus nasutus Kurz (Acanthaceae). This compound has potential therapeutic value as an anticancer and antiviral agent. The purposes of this study were to determine the effects of this compound on the function and the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2), using the in vitro model of Caco-2 cells.

Spray-dried chitosan microparticles for cellular delivery of an antigenic protein: physico-chemical properties and cellular uptake by dendritic cells and macrophages.

Purpose: Spray-dried chitosan microparticles for cellular delivery of antigen to dendritic cells (DC) and macrophages (Mϕ) were investigated.

Methods: Chitosan microparticles were prepared by spray drying. For comparison, poly(lactic-co-glycolic acid) (PLGA) and poly(α-butyl cyanoacrylate) (BCA) micro-/nanoparticles were generated.

Phyllanthin and hypophyllanthin inhibit function of P-gp but not MRP2 in Caco-2 cells.

Objectives: The purposes of this study were to investigate the inhibitory effects of two lignans, phyllanthin and hypophyllanthin, on the function of P-glycoprotein (P-gp) and multidrug resistance protein 2 (MRP2), using the in-vitro model of Caco-2 cells. In addition, the effect of prolonged exposure to these two compounds on the expression of active P-gp was also determined.

Methods: The activity of P-gp and MRP2 was determined in the uptake assays by monitoring the intracellular accumulation of their specific substrates (calcein acetoxymethyl ester and 5(6)-carboxy-2',7'-dichlorofluorescein diacetate, respectively) with fluorescence spectroscopy.

Effect of cholesterol on the properties of spray-dried lysozyme-loaded liposomal powders.

The influence of cholesterol (Chol) in the liposomal bilayer on the properties of inhalable protein-loaded liposomal powders prepared by spray-drying technique was investigated. Lysozyme (LSZ) was used as a model protein. Feed solution for spray drying was prepared by direct mixing of aqueous solution of LSZ with mannitol solution and empty liposome dispersions composed of hydrogenated phosphatidylcholine and Chol at various molar ratios.

Influence of incorporation methods on partitioning behavior of lipophilic drugs into various phases of a parenteral lipid emulsion.

The purpose of this study was to investigate the effect of drug incorporation methods on the partitioning behavior of lipophilic drugs in parenteral lipid emulsions. Four lipophilic benzodiazepines, alprazolam, clonazepam, diazepam, and lorazepam, were used as model drugs. Two methods were used to incorporate drugs into an emulsion: dissolving the compound in the oil phase prior to emulsification (de novo emulsification), and directly adding a concentrated solution of drug in a solubilizer to the emulsion base (extemporaneous addition).

Preparation and characterization of propylthiouracil niosomes.

Propylthiouracil, a lyophobic drug with an antiproliferative activity, was formulated into niosomes using various classes of nonionic surfactants. Feasibility of vesicle formation by the sonication method was evaluated. Size and size distribution was measured by laser diffraction.

The influence of physicochemical properties of preservative compounds on their distribution into various phases of oil in water submicron emulsion.

Phospholipids--stabilized submicron emulsions require the addition of preservatives to destroy or inhibit the growth of microorganisms when these preparations are non-sterile products or when packed in multi-dose containers. This study examined the distribution of four paraben esters--methylparaben, ethylparaben, propylparaben, and butylparaben--that were added into submicron emulsions by de novo emulsification. The distribution of preservative compounds among different phases was determined after separation of submicron emulsions by ultracentrifugation.

Synergistic effect of phospholipid-based liposomes and propylthiouracil on U-937 cell growth.

Scientific evidence indicates that exogenous phospholipids in the form of liposomes can affect cell growth. Effects of liposomes on cell growth depend on several factors including composition of liposomes, lipid concentration, and type of cells studied. Because phagocytic cells such as monocytes and macrophages are natural targets of liposomes, intracellular delivery of drugs to modulate cellular activity of these cells is of interest.