Gallic Acid Derivatives Research Articles

Phenolic Compound Profiles, Antioxidant, and Cytoprotective Activity of Elaeagnus conferta Roxb. Fruit.

In this paper, three varieties of Elaeagnus conferta Roxb fruits prepared by ultrasonic-assisted extraction from a subtropical region southwest of China were utilized as raw materials to investigate their phenolic profiles, antioxidant activities, and protective effects on injured human umbilical vein endothelial cells (HUVECs). The ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) findings revealed that fifteen substances, including seven phenolic acids, seven flavonoids, and one gallic acid derivative, were discovered. The dihydromyricetin, ellagic acid, gallic acid were the predominant phenolic compounds in all E.conferta fruits. These E.conferta fruits extracts shown excellent antioxidant activity varied from 2.258±0.03~7.844±0.39 μM Trolox/g and protective effect on HUVECs injured by H2O2 through decrease the level of ROS, MDA, LDH and enhance the SOD level. These finding indicate that E.conferta is a valuable source of high-capacity antioxidants that might be used as an alternative material for food industries.

Influence of altitudes and development stages on the chemical composition and antioxidant capacity of Andean blackberries (Rubus glaucus Benth)

BackgroundThe Andean blackberry (Rubus glaucus Benth), locally known as “Mora de Castilla,” is a high-altitude fruit rich in phytochemicals, mainly anthocyanins, with potent antioxidant properties. Although its chemical composition has been studied, the influence of altitude on its phytochemical profile and antioxidant capacity is still unclear. This research aimed to investigate the effects of development stages and altitude on the phytochemical profile and antioxidant activity of this fruit.MethodsAndean blackberry fruits were collected at different altitudes and development stages in the central Andean region of Ecuador. An hydroalcoholic extraction was used to quantify the compounds and determine the total antioxidant activity, while solid phase extraction (SPE) was performed to separate anthocyanins from other compounds. Ultra-high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer (HPLC-DAD/ESI-MSn) was used to identify anthocyanin and non-anthocyanin phenols, while total antioxidant capacity, total polyphenols, total flavonoid content, and total anthocyanin content were quantified spectrophotometrically.ResultsFlavonols and anthocyanins constitute the majority of the flavonoids identified in the Andean blackberry extracts, both in terms of peak areas and number of identified compounds, followed by ellagic and gallic acid derivatives, as well as phenolic acids, mainly hydroxycinnamic acids. Quercetin was identified as the predominant flavonol in unripe berries, where anthocyanins were not significantly present. On the contrary, in ripe berries, cyanidin and its glycosides stood out as the main anthocyanins and predominant compounds. We observed that in the early stages of ripening, the total polyphenol content predominates in the berries and is mainly responsible for their antioxidant capacity. However, as the fruit ripens, the total anthocyanin content increases, becoming the most prominent bioactive compounds in fully ripe berries.ConclusionThe results suggest that higher altitude environmental conditions may improve the composition, concentration of phenolic compounds, and antioxidant activity of Andean blackberries. Overall, our findings highlight the high functional value of this fruit, supporting its health-protective effects when consumed regularly, either as fresh fruit or in nutraceutical form.

Synergystic effects of binary mixtures of δ-tocopherol and gallic acid derivatives on peroxidation of soybean oil-in-water emulsions

Synergystic effects of binary mixtures of δ-tocopherol and gallic acid derivatives on peroxidation of soybean oil-in-water emulsions

Brazil Nut Semi-Defatted Flour Oil: Impact of Extraction Using Pressurized Solvents on Lipid Profile, Bioactive Compounds Composition, and Oxidative Stability.

Brazilian nuts are native to the Amazon rainforest and are considered a non-timber forest-product of extreme economic importance to local populations. This study evaluated the lipid profile, bioactive compounds, and oxidative stability of semi-defatted Brazilian nut flour oil (BNSDFO) obtained using pressurized fluids (n-propane at 40 °C and 2, 4, and 8 MPa or a CO2/n-propane mixture at 40 °C and 12 MPa). A Brazilian nut kernel oil (BNKO) processed by conventional cold pressing was also obtained. The BNKO showed a higher concentration of total phenolic compounds and saturated fatty acids, higher antioxidant activity, and the presence of gallic acid derivatives. The oils extracted using pressurized fluids showed a higher concentration of linoleic acid, β-sitosterol, and polyunsaturated fatty acids. The utilization of pressurized n-propane resulted in higher yields (13.7 wt%), and at intermediate pressures (4 MPa), the product showed myricetin 3-O-rhamnoside and higher oxidative stability (OSI, 12 h) than at lower pressures (2 MPa). The CO2/n-propane mixture of pressurized solvents resulted in higher concentrations of squalene (4.5 times), the presence of different phenolic compounds, and a high OSI (12 h) but lower yield (2.2 wt%). In conclusion, oils with better fatty acid profiles (oleic e linoleic acids), phytosterol composition, and suitable radical scavenging activity may be obtained using pressurized fluids and Brazilian nut flour, a byproduct of oil extraction. The mixture of solvents may improve the concentration of squalene, whereas using only n-propane may increase oil yield.

Phytochemical profile and allelopathic activity of eight Eucalyptus species on the performance of initial growth stage of four local species in the southern Tunisia

We aimed thought this survey 1) to investigate and compare the phytotoxicity features of eight Eucalyptus species frequently planted in southern Tunisia (Eucalyptus camaldulensis Dehn., Eucalyptus gomphocephala DC., Eucalyptus torquata Luehm., Eucalyptus microtheca F.Muell., Eucalyptus occidentalis Endl., Eucalyptus diversifolia Bonpl., Eucalyptus sargentii Maiden., and Eucalyptus torwood) on seed germination and radicle growth of Medicago sativa L., Corchorus olitorius L., Cenchrus ciliaris L., Peganum harmala L., and 2) to classify those species according to their allelopathic efficiency. The laboratory experiment was conducted using aqueous extracts made from dried and ground plant leaves to obtain concentrations of 5 % and 10 %. These were prepared alongside control treatments for comparison. Afterward, methanol extracts were utilized in the chemical composition identification procedure via HPLC-DAD-ESI-MS. Different responses were obtained for the species studied for germination and extraction. Results highlighted that C. ciliaris and P. harmala were the most susceptible to eucalypt extracts, while, M. sativa and C. olitorius were more resistant. Statistically, lower concentrations were less effective, but higher ones had noticeable inhibitory effects on seedling growth parameters. We assumed that E. occidentalis, E. gomphocephala, E. torquata and E. camaldulensis were recognized as the most noxious species, E. sargentii and E. microtheca produced moderate effects, while E. torwood and E. diversifolia were regarded as benign species. Phytochemicals especially ellagitannins and flavonols derivatives were the major compounds identified accounted for 21–78 % and 8–59 %, but hydroxycinnamic acids derivatives, gallic acid derivatives, total flavonols content and non-phenolic acids were acknowledged as the major causes for the observed outcomes.

Antimigratory Effect of Lipophilic Cations Derived from Gallic and Gentisic Acid and Synergistic Effect with 5-Fluorouracil on Metastatic Colorectal Cancer Cells: A New Synthesis Route.

Colorectal cancer (CRC) is the third leading cause of cancer deaths in the world. Standard drugs currently used for the treatment of advanced CRC-such as 5-fluorouracil (5FU)-remain unsatisfactory in their results due to their high toxicity, high resistance, and adverse effects. In recent years, mitochondria have become an attractive target for cancer therapy due to higher transmembrane mitochondrial potential. We synthesized gallic acid derivatives linked to a ten-carbon aliphatic chain associated with triphenylphosphonium (TPP+C10), a lipophilic cationic molecule that induces the uncoupling of the electron transport chain (ETC). Other derivatives, such as gentisic acid (GA-TPP+C10), have the same effects on colorectal cancer cells. Although part of our group had previously reported preparing these structures by a convergent synthesis route, including their application via flow chemistry, there was no precedent for a new methodology for preparing these compounds. In this scenario, this study aims to develop a new linear synthesis strategy involving an essential step of Steglich esterification under mild conditions (open flask) and a high degree of reproducibility. Moreover, the study seeks to associate GA-TPP+C10 with 5FU to evaluate synergistic antineoplastic effects. In addition, we assess the antimigratory effect of GA-TPP+C10 and TPP+C10 using human and mouse metastatic CRC cell lines. The results show a new and efficient synthesis route of these compounds, having synergistic effects in combination with 5FU, increasing apoptosis and enhancing cytotoxic properties. Additionally, the results show a robust antimigratory effect of GATPP+C10 and TPP+C10, reducing the activation pathways linked to tumor progression and reducing the expression of VEGF and MMP-2 and MMP-9, common biomarkers of advanced CRC. Moreover, TPP+C10 and GA-TPP+C10 increase the activity of metabolic signaling pathways through AMPK activation. The data allow us to conclude that these compounds can be used for in vivo evaluations and are a promising alternative associated with conventional therapies for advanced colorectal cancer. Additionally, the reported intermediates of the new synthesis route could give rise to analog compounds with improved therapeutic activity.

Comprehensive phytochemical profiling of Phyllanthus emblica L. flowers on UHPLC/MS quadrupole time of flight, HPTLC, HPLC, and NMR analytical platforms reveals functional metabolites with potent anti-inflammatory effects in human (THP-1) macrophages.

Phyllanthus emblica L., renowned for its pharmacological benefits found in its fruits and leaves, has received considerable attention. However, there is a notable lack of research on its flowers, specifically on metabolite profiling and pharmacological activity. The present study aims to delineate the phytochemical constituents of hydromethanolic extract of P.emblica flowers by ultra-high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UHPLC-QToF-MS), high-performance thin layer chromatography (HPTLC), high-performance liquid chromatography (HPLC), infrared and nuclear magnetic resonance spectroscopic methods and subsequent evaluation of its anti-inflammatory potential. The identification and characterization of phytochemicals in P.emblica flowers was performed by UHPLC/MS-QToF in both positive and negative ionization modes. Additionally, marker compounds present in flower extract were analyzed using HPTLC, HPLC, FT-IR, and NMR methods. The anti-inflammatory potential was evaluated in lipopolysaccharide-stimulated THP-1 macrophages by evaluating inflammatory biomarkers. UHPLC/MS-QToF analysis facilitated the identification of 51 compounds from P.emblica flowers including gallic acid derivatives, flavonoid glycosides, and tannins based on their fragmentation patterns and previous literature reports. Notably, the study also identified spermidine compounds for the first time in this species. Optimization of HPTLC and HPLC methods marked the presence of corilagin as major compound followed by FT-IR and NMR spectral methods. Moreover, treatment with hydromethanolic extract of P.emblica flowers resulted in decreased levels of proinflammatory cytokines, TNF-α, IL-1β, and IL-6, alongside modulation of nuclear factor-κB activity in lipopolysaccharide-induced THP-1 macrophages. Chromatographic techniques in conjunction with spectral methods found robust prevalence in the identification of signature phytometabolites present in P. emblica flowers, which sets the basis for its anti-inflammatory potentials. The studies established a foundation for further exploration of potential applications of P. emblica flowers across various domains.

Microbial synthesis of gallic acid and its glucoside β-glucogallin.

Gallic acid (GA) and β-glucogallin (BGG) are natural products with diverse uses in pharmaceutical, food, chemical and cosmetic industries. They are valued for their wide-ranging properties such as antioxidant, antibacterial, antidiabetic, and anticancer properties. Despite their significant importance, microbial production of GA and BGG faces challenges such as limited titers and yields, along with the incomplete understanding of BGG biosynthesis pathways in microorganisms. To address these challenges, we developed a recombinant Escherichia coli strain capable of efficiently producing GA. Our approach involved screening efficient pathway enzymes, integrating biosynthetic pathway genes into the genome while balancing carbon flux via adjusting expression levels, and strengthening the shikimate pathway to remove bottlenecks. The resultant strain achieved impressive results, producing 51.57 g/L of GA with a carbon yield of 0.45 g/g glucose and a productivity of 1.07 g/L/h. Furthermore, we extended this microbial platform to biosynthesize BGG by screening GA 1-O-glucosyltransferase, leading to the de novo production of 92.42 mg/L of BGG. This work establishes an efficient chassis for producing GA at an industrial level and provides a microbial platform for generating GA derivatives.

Unlocking the nutraceutical potential of Corylus avellana L. shells: microwave-assisted extraction of phytochemicals with antiradical and anti-diabetic properties.

In recent years, the demand for high-quality natural extracts to be included in nutraceutical formulations has increased sharply. Hazelnut (Corylus avellana L.) shells (HZS) are underrated agricultural by-products that could be exploited as a source of active ingredients with pro-healthy properties. In the present study, a fully green microwave-assisted extraction (MAE) method was established for the first time aiming to recover bioactive constituents from HZS with significant nutraceutical value. Key MAE parameters, including ethanol in water concentration, microwave power, irradiation time and solvent-to-powder ratio, were optimized through response surface methodology utilizing a Box-Behnken design to achieve the highest total phenolic content and antioxidant/antiradical activities in the final extract. The optimal MAE conditions (28% v/v ethanol/water, 270 s, 670 W, and 37 mL g-1) yielded an extract with significant scavenging capacity against reactive oxygen species and remarkable inhibitory activity towards both α-amylase (IC50 = 7.73 μg mL-1) and α-glucosidase (IC50 = 49.44 μg mL-1), demonstrating stronger hypoglycaemic properties than the anti-diabetic drug acarbose. Additionally, fluorescence spectroscopy results highlighted the ability of the optimized extract from HZS (OHS-E) to counteract advanced glycation end-product formation throughout the glycation cascade in a dose-dependent manner. Liquid chromatography/electrospray ionization-tandem mass spectrometry profiling unveiled the presence of fatty acids and phenolic compounds, including lignans, flavonoids, gallic acid derivatives and diarylheptanoids. Lastly, the biocompatibility of OHS-E was attested on HT29-MTX and Caco-2 intestinal cells. Altogether, these findings encourage the potential application of OHS-E as an effective nutraceutical component against type 2 diabetes mellitus and oxidative stress. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Docking and Simulation Studies on Novel Analogues of 3,4,5-Trihydroxy Benzoic Acid as HSP90Alpha Inhibitors

Abstract: HSP90 assists as a crucial molecular chaperone that responds to environmental stressors and helps in the survival of cells in microorganisms. This protein is integral to the stress response, aiding in the stabilization of various proteins essential for microbial survival. Consequently, the ability of a number of tissues to adjust to endogenous stress depends critically on appropriate chaperone activity. Modulators of chaperone activity, however, have emerged as a novel and developing area of drug discovery due to the association between changed chaperone function and the development of numerous illnesses. Inhibition of HSP90alpha can disrupt proper protein folding, thus impairing growth and virulence in fungi. In this work, we selected novel leads of gallic acid derivatives with the help of OSIRIS Property Explorer and DruLiTo software. Selected leads were subjected to ADME-T studies for further screening. Docking and molecular simulation studies on selected compounds were performed using Schrodinger v21 and GROMACS software to predict the bioactivity of novel leads of 3,4,5 trihydroxy benzoic acid for suppression of the HSP90alpha enzyme. Compounds 4N, 18N, 15N, and 14N showed good docking scores of -6.5, -6.4, -5.91, and -5.98, respectively, which was comparable to standard ciprofloxacin. Compound 4N and compound 14N demonstrated notable binding interactions and were selected for further investigation through molecular dynamics studies with HSP90alpha (PDB ID: 1YC1). RMSD, H BOND, and RMSF analysis confirmed the stable binding of compounds 4N and 14 N with the HSP90 enzyme. The RMSF plot showed less than 0.35 nm fluctuation for the HSP90alpha enzyme in complex with different ligands. It can be concluded that ligand binding can cause stability to the conformation of the protein. Compounds 4N and 14N are considered to be the best theoretical lead, which can further be studied experimentally as HSP90 alpha inhibitors for antimicrobial activity. other: Ongoing research aims to uncover more insights into the specific mechanisms of action, optimize structural features for enhanced efficacy, and explore potential synergies with existing antimicrobial agents. As a result, these derivatives hold promise as candidates for the development of novel antimicrobial agents with a broad spectrum of activity against bacteria and fungi

Identification, Bioaccessibility, and Antioxidant Properties of Phenolic Compounds in Carob Syrup.

Carob syrup is a brown, thick syrup produced from carob pulp that can be directly consumed or used as a sweetener, which also finds applications in folk medicinal practices. In this work, the quali-quantitative phenolic profile of five different carob syrups was elucidated before and after in vitro gastro-intestinal digestion. Moreover, the anti-oxidant properties of undigested and digested carob syrups were investigated. A total of 75 phenolic compounds were identified in undigested carob syrups. The most important phenolic compound in all the samples was gallic acid, the concentration of which ranged between 54.28 and 117.73 mg/100 g. Additional compounds belonging to the classes of hydroxybenzoic acids (in particular glycosylated gallic acid derivatives), hydroxycinnamic acids, and flavonoids (especially flavonols) were also identified. During in vitro gastric digestion, gallic acid mono- and di-hexosides were diglycosylated, releasing gallic acid, which was further degraded in ellagic acid through oxidative polymerization in the intestinal phase of the digestion. Ellagic acid was the major compound detected after in vitro gastro-intestinal digestion of carob syrups. With few exceptions, the anti-oxidant properties of carob syrup were preserved even after digestion. Carob syrup can be considered an important source of phenolic compounds with demonstrated positive effects on human health.

Exploring the Anti-Inflammatory and Antioxidant Potential, Metabolite Composition and Inorganic Profile of Cistus monspeliensis L. Aerial Parts and Roots.

This work focuses on Cistus monspeliensis L. aerial parts (AP) and roots (R) extracts, investigating the anti-inflammatory and antioxidant potential of the two organs in comparison. At dosages between 1.56 and 6.25 µg/mL, both extracts showed a protective effect against LPS inflammatory stimulus on a macrophage cell line (RAW 264.7). Interestingly, only R was able to significantly reduce both IL-1β and IL-6 mRNA gene expression in the presence of LPS. Moreover, the treatment of a neuroblastoma cell line (SH-SY5Y) with AP and R at 6.25 µg/mL increased the cell survival rate by nearly 20% after H2O2 insult. However, only R promoted mitochondria survival, exhibited a significantly higher production of ATP and a higher activity of the enzyme catalase than the control. Both AP and R had similar primary metabolites; in particular, they both contained 1-O-methyl-epi-inositol. Labdane and methoxylated flavonoids were the most characteristic compounds of AP, while R contained mainly catechins, gallic acid, and pyrogallol derivatives. Considering the importance of elemental composition in plants, the inorganic profile of AP and R was also investigated and compared. No potentially toxic elements, such as Pb, were detected in any sample.

Impact of Drying Method and Solvent Extraction on Ethiopian Verbascum sinaiticum (Qetetina) Leaves: Metabolite Profiling and Evaluation of Antioxidant Capacity

The aim of this study was to evaluate the effects of different drying methods on bioactive compounds and to analyze their composition in Verbascum sinaiticum (V. sinaiticum) leaf extracts using UHPLC-ESI-QTOF-MS/MS. V. sinaiticum is traditionally used as an herbal medicine, yet it has undergone limited scientific investigations regarding its secondary metabolites. V. sinaiticum leaves were dried using oven dryers at 50 °C, 60 °C, and 70 °C, as well as a freeze dryer. The leaves were then extracted using 50% and 70% aqueous ethanol and 100% aqueous solutions. The results showed that the highest contents of TPC and TFC were observed when 70% aqueous ethanol was used during freeze drying, reaching 181.73 mg GAE/g dw and 78.57 mg CE/g dw, respectively. The strongest correlations were observed between the TFC and DPPH radical scavenging activity (0.9082), followed by TPC and ABTS assays (0.8933) and TPC and DPPH (0.8272). In the FTIR analysis, freeze drying exhibited a lower intensity of the phenolic -OH functional groups, contrasting with significant denaturation observed during oven drying at 70 °C. Metabolite analysis identified 29 compounds in V. sinaiticum leaves, further confirming the presence of 14 phenolic and flavonoid compounds, including kaempferol, catechin, gallic acid, and myricetin derivatives, consistent with the experimentally observed antioxidant capacity. This study highlights the impact of drying methods on the bioactive composition of V. sinaiticum and underscores its potential as a source of antioxidants for food, nutraceutical, and pharmaceutical applications.

Study on the Antifungal Activity of Gallic Acid and Its Azole Derivatives against Fusarium graminearum.

The wheat scab caused by Fusarium graminearum (F. graminearum) has seriously affected the yield and quality of wheat in China. In this study, gallic acid (GA), a natural polyphenol, was used to synthesize three azole-modified gallic acid derivatives (AGAs1-3). The antifungal activity of GA and its derivatives against F. graminearum was studied through mycelial growth rate experiments and field efficacy experiments. The results of the mycelial growth rate test showed that the EC50 of AGAs-2 was 0.49 mg/mL, and that of AGAs-3 was 0.42 mg/mL. The biological activity of AGAs-3 on F. graminearum is significantly better than that of GA. The results of field efficacy tests showed that AGAs-2 and AGAs-3 significantly reduced the incidence rate and disease index of wheat scab, and the control effect reached 68.86% and 72.11%, respectively. In addition, preliminary investigation was performed on the possible interaction between AGAs-3 and F. graminearum using density functional theory (DFT). These results indicate that compound AGAs-3, because of its characteristic of imidazolium salts, has potential for use as a green and environmentally friendly plant-derived antifungal agent for plant pathogenic fungi.

Characterization of flours from the aroeira leaf (Schinus terebinthifolius Raddi), obtained by different drying methods

The present work aimed at the development and characterization of aroeira leaf flour (Schinus terebinthifolius Raddi), obtained by lyophilization and drying in an air circulation oven. The technological, physical, physico-chemical, morphological, functional, and microbiological aspects were analyzed. Physico-chemical analysis identified the following properties with values provided respectively for fresh leaves (FOin) and flours (FES and FLIO): low water activity (0.984, 0.370, 0.387 g/100 g), moisture (64.52, 5.37, 7.97 g /100 g), ash (2.69, 6.51, and 6.89 g/100 g), pH (0.89, 4.45, 4.48 g/100 g), lipids (0.84, 1.67, 5.23 g/100 g), protein (3.29, 8.23, 14.12 g/100 g), carbohydrates (17.02, 53.12, 33.02 g/100 g), ascorbic acid (19.70, 34.20, 36.90 mg/100 g). Sources of fiber from plant leaves and flours (11.64, 25.1, 32.89 g/100 g) showed increased levels of luminosity. For NMR, the presence of aliphatic and aromatic compounds with olefinic hydrogens and a derivative of gallic acid were detected. The most abundant minerals detected were potassium and calcium. Micrographs identified the presence of irregular, non-uniform, and sponge-like particles. The main sugars detected were: fructose, glucose, and maltose. Malic, succinic, citric, lactic, and formic acids were found. Fifteen phenolic compounds were identified in the samples, highlighting: kaempferol, catechin, and caffeic acid. The values ​​found for phenolics were (447, 716.66, 493.31 mg EAG/100 g), flavonoids (267.60, 267.60, 286.26 EC/100 g). Antioxidant activity was higher using the ABTS method rather than FRAP for analysis of FOin, FES, and FLIO. Since the flours of the aroeira leaf have an abundant matrix of nutrients with bioactive properties and antioxidant activity, they have a potential for technological and functional use when added to food.

Chromophores in spinning dopes of cellulose and imidazolium ionic liquids

AbstractSpinning of cellulose dissolved in 3-alkyl-1-methylimidazolium ionic liquids is a current approach to manmade cellulosic fibers. To curb cellulose degradation in the dope, stabilizers have to be used. Generation of chromophores in the dope and the resulting fibers is unavoidable, with most of the discoloration resulting from the employed antioxidants. In the present work, the chemical structures of the chromophores derived from the most common “green” stabilizers currently used, namely propyl gallate (a gallic acid derivative), hydroxytyrosol (and antioxidant from olives), and tocopheramines (vitamin E derivatives), were elucidated by a combination of analytical techniques and final confirmation by comparison with independently synthesized samples. While most compounds are oxidation and rearrangement products of the antioxidants themselves, coupling products with the ionic liquid´s imidazolium cations were also found. Identification of the colored compounds is a critical issue for both the optimization of fiber bleaching steps and solvent purification/recovery in the spinning process. Now that the nature of the generated chromophores is known, milder yet more effective bleaching treatments can be developed and solvent purification/recycling can be specifically optimized.

Synergistic Antibacterial Activity of Gallic Acid Based Chalcone Indl 2 by Inhibiting Efflux Pump Transporters.

As a part of novel discovery of drugs from natural resources, present study was undertaken to explore the antibacterial potential of chalcone Indl-2 in combination with different group of antibiotics. MIC of antibiotics was reduced up to eight folds against the different cultures of E. coli by both chalcones. Among the two compounds, the i. e. 1-(3', 4,'5'-trimethoxyphenyl)-3-(3-Indyl)-prop-2-enone (6, Indl-2), a chalcone derivative of gallic acid (Indl-2) was better along with tetracycline (TET) worked synergistically and was found to inhibit efflux transporters as obvious by ethidium bromide efflux confirmed by ATPase assays and docking studies. In combination, Indl-2 kills the MDREC-KG4 cells, post-antibiotic effect (PAE) of TET was prolonged and mutant prevention concentration (MPC) of TET was also decreased. In-vivo studies revealed that Indl-2 reduces the concentration of TNF-α. In acute oral toxicity study, Indl-2 was non-toxic and well tolerated up-to dose of 2000 mg/kg. Perhaps, the study is going to report gallic acid derived chalcone as synergistic agent acting via inhibiting the primary efflux pumps.

The Protective Effects of Syringic Acid on Bisphenol A-Induced Neurotoxicity Possibly Through AMPK/PGC-1α/Fndc5 and CREB/BDNF Signaling Pathways.

Bisphenol A (BPA), an endocrine disruptor, is commonly used to produce epoxy resins and polycarbonate plastics. Continuous exposure to BPA may contribute to the development of diseases in humans and seriously affect their health. Previous research suggests a significant relationship between the increased incidence of neurological diseases and the level of BPA in the living environment. Syringic acid (SA), a natural derivative of gallic acid, has recently considered much attention due to neuromodulator activity and its anti-oxidant, anti-apoptotic, and anti-inflammatory effects. Therefore, in this study, we aimed to investigate the effects of SA on oxidative stress, apoptosis, memory and locomotor disorders, and mitochondrial function, and to identify the mechanisms related to Alzheimer's disease (AD) in the brain of rats receiving high doses of BPA. For this purpose, male Wistar rats received BPA (50, 100, and 200mg/kg) and SA (50mg/kg) for 21days. The results showed that BPA exposure significantly altered the rats' neurobehavioral responses. Additionally, BPA, by increasing the level of ROS, and MDA level, increased the level of oxidative stress while reducing the level of antioxidant enzymes, such as SOD, CAT, GPx, and mitochondrial GSH. The administration of BPA at 200mg/kg significantly decreased the expression of ERRα, TFAM, irisin, PGC-1α, Bcl-2, and FNDC5, while it increased the expression of TrkB, cytochrome C, caspase 3, and Bax. Moreover, the Western blotting results showed that BPA increased the levels of P-AMPK, GSK3b, p-tau, and Aβ, while it decreased the levels of PKA, P-PKA, Akt, BDNF, CREB, P-CREB, and PI3K. Meanwhile, SA at 50mg/kg reversed the behavioral, biochemical, and molecular changes induced by high doses of BPA. Overall, BPA could lead to the development of AD by affecting the mitochondria-dependent apoptosis pathway, as well as AMPK/PGC-1α/FNDC5 and CREB/BDNF/TrkB signaling pathways, and finally, by increasing the expression of tau and Aβ proteins. In conclusion, SA, as an antioxidant, significantly reduced the toxicity of BPA.

Processing of Reynoutria multiflora: transformation of catechin and gallic acid derivatives and their identification.

Introduction: The root of Reynoutria multiflora (Thunb.) Moldenke (RM) has been used widely in formulations of herbal medicines in China for centuries. Raw R. multiflora (RRM) should be processed before use to reduce toxicity and increase efficacy. However, detailed regulation of the processing endpoint is lacking, and the duration of processing can vary considerably. We conducted in-depth research on stilbene glycosides in RM at different processing times. Previously, we discovered that 219 stilbene glycosides changed markedly in quantity and content. Therefore, we proposed that processing causes changes in various chemical groups. Methods: To better explain the mechanism of RM processing for toxicity reduction and efficacy enhancement, we used a method of tandem mass spectrometry described previously to research gallic acid based and catechin based metabolites. Results: A total of 259 metabolites based on gallic acid and 112 metabolites based on catechins were identified. Among these, the peak areas of 157 gallic acid and 81 catechins gradually decreased, those of another 71 gallic acid and 30 catechins first increased and then decreased, those of 14 gallic acid and 1 catechin gradually increased. However, 17 of the gallic acids showed no significant changes. We speculate that many gallic acid metabolites hydrolyze to produce gallic acid; moreover, the dimers/trimers of catechins, after being cleaved into catechins, epicatechin, gallic acid catechins, and epicatechin monomers, are cleaved into gallic acid and protocatechualdehyde under high temperature and high humidity, subsequently participating in the Maillard reaction and browning reactions. Discussion: We showed that processing led to changes in chemical groups, clarification of the groups of secondary metabolites could provide a basis for research on the pharmacological and toxic mechanisms of RM, as well as the screening of related markers.

OVICIDAL AND LARVICIDAL EFFECTS OF A HYDROALCOHOLIC EXTRACT FROM Cyrtocarpa procera LEAVES AGAINST Haemonchus contortus

This study evaluated the ovicidal and larvicidal effects of a hydroalcoholic extract (HAE) and two fractions—one aqueous (Aq-F) and the other organic (EtOAc-F)—from dehydrated Cyrtocarpa procera leaves on Haemonchus contortus. In addition, the primary compounds in the HAE and the fractions were identified. The egg hatching inhibition (% EHI) and L3 larval mortality (% Mortality) tests were performed. The treatments used in the EHI test were HAE (12.5–200 mg mL-1), Aq-F (5 and 10 mg mL-1), and EtOAc-F (0.62–10 mg mL-1); for larval mortality, HAE (50–200 mg mL-1), Aq-F (20–40 mg mL-1), and EtOAc-F (2.5–40 mg mL-1). Thiabendazole (0.1 mg mL-1) and ivermectin (5 mg mL-1) were used as positive controls, while methanol (3 %) and distilled water were negative controls. The results were analyzed using a completely randomized design and an ANOVA. The main compounds in the extract and fractions were identified using high-performance liquid chromatography. The HAE had a 100 % ovicidal effect at the highest concentration tested, while EtOAc-F had a nearly 100 % ovicidal effect at 1.25 mg mL-1, and Aq-F displayed the lowest ovicidal effect. Regarding larval mortality, the HAE exerted a larvicidal effect close to 80 % at 100 mg mL-1, while EtOAc-F displayed a larval mortality of 71.47 % at 20 mg mL-1. The chemical analysis indicated the presence of gallic acid, derivatives of gallic acid (gallates), kaempferol rutinoside, quercetin glycoside, and luteolin glycoside. This study shows evidence of the ovicidal and larvicidal properties of C. procera, which could make it useful as a natural anthelmintic in the control of H. contortus.