Effects of Syringic Acid on Apoptosis, Inflammation, and AKT/mTOR Signaling Pathway in Gastric Cancer Cells

Gastric cancer is one of the most common cancer and deadly disease worldwide. Despite substantial advances made in the treatment of gastric cancer, existing therapies still encounter bottlenecks. Chemotherapy, for instance, could lead to serious side effects, high drug resistance and treatment failure. Phytochemical-derived compounds from plants offer novel strategies as potent drug molecules in cancer therapy. Given the low toxicity and higher tolerance rate of naturally occurring compounds, the present study evaluated the effects of syringic acid on cytotoxicity, oxidative stress, mitochondrial membrane potential, apoptosis, and inflammatory responses in gastric cancer cell line (AGS). AGS cells were treated with various concentrations (5–40 μg/mL) of syringic acid for 24 h, after which cytotoxicity was analyzed. Reactive Oxygen Species (ROS), antioxidant enzyme activities, mitochondrial membrane potential (MMP, Δψm), cell morphologies, the expression of apoptotic markers and protein expression patterns were also investigated. Results indicated that syringic acid-treated cells developed anti-cancer activities by losing MMP, cell viability, and enhancing intracellular ROS. Syringic acid selectively developed apoptosis in a dose-dependent manner via enhanced regulation of caspase-3, caspase-9 and Poly ADP-ribose Polymerase (PARP) whereas decreasing the expression levels of p53 and BCL-2. Syringic acid also lowered activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) whereas Thio Barbituric Acid Reactive Substances (TBARS) increased. Syringic acid suppressed gastric cancer cell proliferation, inflammation, and induced apoptosis by upregulating mTOR via AKT signaling pathway. The study suggests syringic acid may constitute a promising chemotherapeutic candidate for gastric cancer treatment. Our study is the first report on the anti-cancer effects of syringic acid against gastric cancer cells via apoptosis, inhibition of inflammation, and the suppression of the mTOR/AKT signaling pathway

Use of superheated liquids for the extraction of non-volatile compounds from wood: HPLC studies

A study of the extraction of oak wood compounds using superheated water-ethanol mixtures ranging from 10 to 60% ethanol is reported. Identification and characterization of the extracted compounds have been made by high performance liquid chromatography. The extraction has been performed using the static mode by single or repetitive cycles. The variables affecting the extraction process have been studied and their optimum values established (extraction time: 50 min; pressure: 40 atm; extraction temperature: 180º C). The study allows to compare the non-volatile polyphenol fractions obtained in this way with those present in commercial samples with fully agreement between them. In addition, the method allows manipulation of the extract composition by changing the working pressure, temperature and water-ethanol ratio

Rapid determination of simple polyphenols in grapes by HPLC using a monolithic column

The development of a rapid, reliable and reproducible LC method for the determination and quantification of 13 polyphenols (gallic acid, protocatechuic aldehyde, gentisic acid, catechin, vanillinic acid, caffeic acid, vanillin, epicatechin, syringaldehyde, p-coumaric acid, ferulic acid, sinapic acid and resveratrol) in grapes and derived products is reported

Recovery of Polyphenols from Brewer’s Spent Grains

peer-reviewedThe recovery of antioxidant polyphenols from light, dark and mix brewer’s spent grain (BSG) using conventional maceration, microwave and ultrasound assisted extraction was investigated. Total polyphenols were measured in the crude (60% acetone), liquor extracts (saponified with 0.75% NaOH) and in their acidified ethyl acetate (EtOAc) partitioned fractions both by spectrophotometry involving Folin–Ciocalteu reagent and liquid-chromatography-tandem mass spectrometry (LC-MS/MS) methods. Irrespective of the extraction methods used, saponification of BSG yielded higher polyphenols than in the crude extracts. The EtOAc fractionations yielded the highest total phenolic content (TPC) ranging from 3.01 ± 0.19 to 4.71 ± 0.28 mg gallic acid equivalent per g of BSG dry weight. The corresponding total polyphenols quantified by LC-MS/MS ranged from 549.9 ± 41.5 to 2741.1 ± 5.2 µg/g of BSG dry weight. Microwave and ultrasound with the parameters and equipment used did not improve the total polyphenol yield when compared to the conventional maceration method. Furthermore, the spectrophotometric quantification of the liquors overestimated the TPC, while the LC-MS/MS quantification gave a closer representation of the total polyphenols in all the extracts. The total polyphenols were in the following order in the EtOAc fractions: BSG light > BSG Mix > BSG dark, and thus suggested BSG light as a sustainable, low cost source of natural antioxidants that may be tapped for applications in food and phytopharmaceutical industries

In silico evaluation of therapeutic potentials of Syringic acid against some selected diseases

In the past few years several developments in medications have been made for the better treatment of certain diseases like Breast Cancer, Alzheimer’s disease, Tuberculosis, Obesity and Malaria. Phytochemicals possessing various medicinal properties have opened up the door to discover or design novel drug against these diseases. Syringic acid is such a natural compound found in many plants with a vast range of therapeutic potentials against several diseases. The present study aims to reveal Syringic acid as a potent inhibitor against Breast Cancer, Alzheimer’s disease, Tuberculosis, Obesity and Malaria comparing to the standard drugs of each disease. Molecular docking of syringic acid with critical proteins associated with the diseases was done using Schrödinger Maestro (v11.1). QikProp module of Schrödinger Maestro was used for ADME prediction and the toxicity of the ligand was evaluated by ProTox online databases. Syringic acid was found to exhibit acceptable ADME properties with no carcinogenicity and mutagenicity. Molecular docking result also showed higher scores compared to the commercially available standard drugs against four out of five diseases. The best docking scores were found against Breast cancer, Alzheimer’s disease, Obesity and Malaria which are -6.801 kcal/mol, -5.285 kcal/mol, -5.491 kcal/mol and -4.141 kcal/mol respectively. Syringic acid can be a stronger inhibitory potential agent against selected diseases than the standard drugs. Further clinical studies are required to consider syringic acid as an effective candidate drug for the better treatment of the mentioned diseases

Phenolic metabolites of anthocyanins following a dietary intervention study in post-menopausal women

Scope Numerous studies feeding anthocyanin-rich foods report limited bioavailability of the parent anthocyanins. The present study explores the identity and concentration of the phenolic metabolites of anthocyanins in humans. Methods and results Anthocyanin metabolites were quantified in samples collected from a previously conducted 12-wk elderberry intervention study in healthy post-menopausal women. Individual 1-, 2- and 3-h post-bolus urine samples and pooled plasma samples following acute (single bolus) and chronic (12-wk supplementation) anthocyanin consumption (500 mg/day) were analysed using HPLC-ESI-MS/MS. Twenty-eight anthocyanin metabolites were identified in urine and 21 in plasma (including sulfates of vanillic, protocatechuic and benzoic acid). Phenolic metabolites reached peak concentrations of 1237 nM in plasma, while anthocyanin conjugates only reached concentrations of 34 nM. Similarly, in urine, phenolic metabolites were detected at concentrations of 33 185 ± 2549 nM/mM creatinine, while anthocyanin conjugates reached concentrations of 548 ± 219 nM/mM creatinine. There was no evidence that chronic exposure had any impact on either the profile or quantity of metabolites recovered relative to acute exposure. Conclusion An extensive range of phenolic metabolites of anthocyanin was identified following elderberry consumption in humans, including 11 novel metabolites, which were identified at much higher concentrations than their parent compounds

Repurposing designed mutants: a valuable strategy for computer-aided laccase engineering – the case of POXA1b

The broad specificity of laccases, a direct consequence of their shallow binding site, makes this class of enzymes a suitable template to build specificity toward putative substrates. In this work, a computational methodology that accumulates beneficial interactions between the enzyme and the substrate in productive conformations is applied to oxidize 2,4-diamino-benzenesulfonic acid with POXA1b laccase. Although the experimental validation of two designed variants yielded negative results, most likely due to the hard oxidizability of the target substrate, molecular simulations suggest that a novel polar binding scaffold was designed to anchor negatively charged groups. Consequently, the oxidation of three such molecules, selected as representative of different classes of substances with different industrial applications, significantly improved. According to molecular simulations, the reason behind such an improvement lies in the more productive enzyme–substrate binding achieved thanks to the designed polar scaffold. In the future, mutant repurposing toward other substrates could be first carried out computationally, as done here, testing molecules that share some similarity with the initial target. In this way, repurposing would not be a mere safety net (as it is in the laboratory and as it was here) but rather a powerful approach to transform laccases into more efficient multitasking enzymes.This work was funded by INDOX (KBBE-2013-7-613549) European project and CTQ2013-48287-R Spanish National Project. V. G. and E. M. acknowledge Università degli Studi di Napoli and Generalitat de Catalunya for their respective predoctoral fellowships.Peer ReviewedPostprint (author's final draft

IN SILICO STUDY OF CHEMICAL COMPOUNDS FROM ARECA NUT (ARECA CATECHU L.) ON GABAA RECEPTOR AS ANTI-INSOMNIA CANDIDATES

Objective: In silico study of chemical compounds from areca nut (Areca catechu) on GABAA receptor as anti-insomnia candidates. Methods: Prediction and molecular docking of chemical compounds from areca nut with GABAA receptors to find out which compounds are most likely to be anti-insomnia therapy candidates. Results: Molecular docking with AutoDock Vina and ADMET prediction via PreADMET website. Molecular docking and ADME predictions show that there is one potential anti-insomnia compound called syringic acid that has the most amino acid residues in common with the native ligand and standard drug compared to other compounds, as well as producing free energy (ΔG) and inhibition constants (Ki) lower than the native ligand. Syringic acid also has a weak bond with plasma proteins. However, in the parameters of toxicity, syringic acid exhibits carcinogenic and mutagenic properties. Conclusion: Based on the results of molecular docking and ADME prediction obtained one compound with the best results can be used as a candidate for anti-insomnia drugs, namely syringic acid

Use of Alternative Wood for the Ageing of Brandy de Jerez

The use of alternative types of wood has arisen for the aging of the Brandy de Jerez, on a pilot plant level. In particular, besides the use of American oak, two more types of oak have been studied, French oak and Spanish oak, allowed by the Technical File for the ID Brandy de Jerez, and chestnut, which, though it is not officially allowed, is a type of wood which had been traditionally used in the area for the aging of wines and distillates. All of them have been studied with different toasting levels: Intense toasting and medium toasting. The study of the total phenolic composition (TPI), chromatic characteristics, organic acids, and sensory analysis have proven that chestnut leads to distillates with a higher amount of phenolic compounds and coloring intensity than oak. This behavior is the opposite as regards the toasting of the wood. Among the different types of oak, Spanish oak produces aged distillates with a higher phenolic composition and a higher color intensity. Regarding tasting, the best-assessed samples were those aged with chestnut, French oak, and American oak, and the assessors preferred those who had used a medium toasting level to those with an intense leve

Qualitative and quantitative phytochemical analysis of different extracts from Thymus algeriensis aerial parts

This study was performed to evaluate the metabolite recovery from different extraction methods applied to Thymus algeriensis aerial parts. A high-performance liquid chromatographic method using photodiode array detector with gradient elution has been developed and validated for the simultaneous estimation of different phenolic compounds in the extracts and in their corresponding purified fractions. The experimental results show that microwave-assisted aqueous extraction for 15 min at 100 C gave the most phenolics-enriched extract, reducing extraction time without degradation effects on bioactives. Sixteen compounds were identified in this extract, 11 phenolic compounds and five flavonoids, all known for their biological activities. Color analysis and determination of chlorophylls and carotenoids implemented the knowledge of the chemical profile of this plant