Pregnane-Oximino-Alkyl-Amino-Ether Compound as a Novel Class of TGR5 Receptor Agonist Exhibiting Antidiabetic and Anti-Dyslipidemic Activities.

Introduction: The present study deals with the synthesis of pregnane-oximino-amino-alkyl-ethers and their evaluation for antidiabetic and anti-dyslipidemic activities in validated animal and cell culture models.

Methods: The effect on glucose tolerance was measured in sucrose-loaded rats; antidiabetic activity was evaluated in streptozotocin (STZ)-induced diabetic rats and genetically diabetic db/db mice; the anti-dyslipidemic effect was characterized in high-fructose, high-fat diet (HFD)-fed dyslipidemic hamsters. The effect on glucose production and glucose utilization was analyzed in HepG2 liver and L6 skeletal muscle cells, respectively.

Photoexcited triclosan induced DNA damage and oxidative stress via p38 MAP kinase signaling involving type I radicals under sunlight/UVB exposure.

Triclosan (TCS) is an antimicrobial preservative used in personal care products. Here, we have studied the phototoxicity, photogenotoxicity of TCS and its molecular mechanism involving p38 mitogen activated protein kinase (MAPK) pathway under UVB/sunlight exposure. We found that TCS showed photodegradation and photoproducts formation under UVB/sunlight.

Piperine attenuates UV-R induced cell damage in human keratinocytes via NF-kB, Bax/Bcl-2 pathway: An application for photoprotection.

Chronic ultraviolet radiation (UV-R) exposure causes skin disorders like erythema, edema, hyperpigmentation, photoaging and photocarcinogenesis. Recent research trends of researchers have focused more attention on the identification and use of photo stable natural agents with photoprotective properties. Piperine (PIP), as a plant alkaloid, is an important constituent present in black pepper (Piper nigrum), used widely in ayurvedic and other traditional medicines and has broad pharmacological properties.

Pharmacokinetic studies of a novel trioxane antimalarial (99/411) in rats and monkeys using LC-MS/MS.

The pharmacokinetic profile of 99/411, a novel anti-malarial drug, was established in rats (12 mg/kg of body weight) and monkeys (20 mg/kg of body weight). Following oral administration, the presence of 99/411 was rapidly determined in rat plasma, tissues, urine, feces and monkey plasma using a validated LC-MS/MS method. The tissue distribution studies in rats indicated that the drug was partially distributed in all major tissues and plasma, and peak concentration levels were achieved within 0.

Photosensitized 2-amino-3-hydroxypyridine-induced mitochondrial apoptosis via Smac/DIABLO in human skin cells.

The popularity of hair dyes use has been increasing regularly throughout the world as per the demand of hair coloring fashion trends and other cosmetic products. 2-Amino-3-hydroxypyridine (A132) is widely used as a hair dye ingredient around the world. We are reporting first time the phototoxicity mechanism of A132 under ambient environmental UV-B radiation.

Photosensitized rose Bengal-induced phototoxicity on human melanoma cell line under natural sunlight exposure.

Rose Bengal (RB) is an anionic water-soluble xanthene dye, which used for many years to assess eye cornea and conjunctiva damage. RB showed strong absorption maxima (λmax) under visible light followed by UV-B and UV-A. RB under sunlight exposure showed a time-dependent photodegradation.

Photoprotective efficiency of PLGA-curcumin nanoparticles versus curcumin through the involvement of ERK/AKT pathway under ambient UV-R exposure in HaCaT cell line.

Curcumin (Cur) has been demonstrated to have wide pharmacological window including anti-oxidant and anti-inflammatory properties. However, phototoxicity under sunlight exposure and poor biological availability limits its applicability. We have synthesized biodegradable and non-toxic polymer-poly (lactic-co-glycolic) acid (PLGA) encapsulated formulation of curcumin (PLGA-Cur-NPs) of 150 nm size range.

Involvement of cathepsin B in mitochondrial apoptosis by p-phenylenediamine under ambient UV radiation.

Paraphenylenediamine (PPD), a derivative of paranitroaniline has been most commonly used as an ingredient of oxidative hair dye and permanent tattoos. We have studied the phototoxic potential of PPD under ambient ultraviolet radiation. PPD is photodegraded and form a novel photoproduct under UV A exposure.

Role of type I & type II reactions in DNA damage and activation of caspase 3 via mitochondrial pathway induced by photosensitized benzophenone.

Sunscreen users have been increased, since excessive sun exposure increased the risk of skin diseases. Benzophenone (BP) and its derivatives are commonly used in sunscreens as UV blocker. Its photosafety is concern for human health.

Preferential desulfurization of dibenzyl sulfide by an isolated Gordonia sp. IITR100.

Several organosulfur compounds are present in the crude oil, and are required to be removed before its processing into transport fuel. For this reason, biodesulfurization of thiophenic compounds has been studied extensively. However, studies on the sulfide compounds are scarce.

Superoxide mediated photomodification and DNA damage induced apoptosis by Benz(a)anthracene via mitochondrial mediated pathway.

Benz(a)anthracene (BA) is an ubiquitous environmental pollutant of polycyclic aromatic hydrocarbon's (PAHs) family. We showed superoxide (O2(-)) catalyzed BA photo modification and apoptosis in HaCaT keratinocytes under sunlight exposure. O2(-) generation was confirmed by quenching through superoxide dismutase (SOD).

Time Course of the Changes in Novel Trioxane Antimalarial 99/411 Pharmacokinetics upon Antiepileptic Drugs Co-Administration in SD Rats.

Objective. The study aimed to evaluate the influences of coadministration of antiepileptic drugs (AEDs) on an antimalarial candidate 99/411 pharmacokinetic (PK) profile. Method.

Pharmacokinetic study and bioavailability of a novel synthetic trioxane antimalarial compound 97/63 in rats.

Single dose pharmacokinetics study of 97/63 (IND191710, 2004), a trioxane antimalarial developed by Central Drug Research Institute, Lucknow, India, was studied in rats following intravenous and oral administration. Serum samples were analysed by HPLC-UV assay. Separation was achieved on a RP-18 column attached with a guard using acetonitrile : phosphate buffer (70 : 30% v/v) with UV detector at wavelength 244 nm.

Attenuated neuroprotective effect of riboflavin under UV-B irradiation via miR-203/c-Jun signaling pathway in vivo and in vitro.

Background: Riboflavin (RF) or vitamin B2 is known to have neuroprotective effects. In the present study, we report the attenuation of the neuroprotective effects of RF under UV-B irradiation. Preconditioning of UV-B irradiated riboflavin (UV-B-RF) showed attenuated neuroprotective effects compared to that of RF in SH-SY5Y neuroblostoma cell line and primary cortical neurons in vitro and a rat model of cerebral ischemia in vivo.

Singlet oxygen mediated DNA damage induced phototoxicity by ketoprofen resulting in mitochondrial depolarization and lysosomal destabilization.

Ketoprofen (KP) is a widely used nonsteroidal anti-inflammatory drug for the treatment of osteoarthritis and various rheumatic diseases. Currently, KP is applied topically on skin as gel to treat symptoms of pain and inflammation. We have studied the photomodification of KP under natural environmental conditions.

Ambient UVA-induced expression of p53 and apoptosis in human skin melanoma A375 cell line by quinine.

This study aimed to analyze the phototoxic mechanism and photostability of quinine in human skin cell line A375 under ambient intensities of UVA (320-400 nm). Photosensitized quinine produced a photoproduct 6-methoxy-quinoline-4-ylmethyl-oxonium identified through LC-MS/MS. Generation of (1)O2, O2(•-), and (•)OH was measured and further substantiated through their respective quenchers.

Photosensitizing mechanism and identification of levofloxacin photoproducts at ambient UV radiation.

Levofloxacin (LVFX) is a broad spectrum third generation fluoroquinolone antibiotic, used in the treatment of severe or life-threatening bacterial infections. Photosensitizing mechanism of LVFX was investigated under the ambient environmental intensities of UV-A, UV-B and sunlight exposure. Phototoxic effects of LVFX were assessed on NIH-3T3 and HaCaT cell lines.

Liquid chromatographic tandem mass spectrometric assay for simultaneous quantification of compound 97/78 and its in vivo metabolite 97/63, a novel trioxane antimalarial, in human plasma and its application to a protein binding study.

A sensitive, selective and specific LC-MS/ MS assay for simultaneous quantification of compound 97/78 and its active in vivo metabolite 97/63, a novel 1,2,4-trioxane antimalarial, in human plasma has been developed and validated using alpha-arteether as internal standard (IS). Extraction from plasma involves a simple protein precipitation method. The analytes were chromatographed on a Columbus C18 column with guard by isocratic elution with acetonitrile:ammonium acetate buffer (10 mM, pH 4.

In-situ absorption, protein binding and pharmacokinetic studies of S002-853, a novel antidiabetic and antidyslipidaemic flavone derivative in rats.

Objectives: The aim of the study was to investigate the in-situ absorption kinetics, plasma protein binding and pharmacokinetic characteristics of a novel synthetic flavone derivative, S002-853, which shows pronounced antidiabetic and antidyslipidaemic activity.

Methods: Quantification of S002-853 in plasma was performed by the LC-MS/MS method and in-situ sample analysis was carried out by the HPLC-UV method.

Key Findings: The absorption rate constant was 0.