Gallic Acid Derivatives Research Articles

UVA, UVB Light Doses and Harvesting Time Differentially Tailor Glucosinolate and Phenolic Profiles in Broccoli Sprouts.

Broccoli sprouts contain health-promoting glucosinolate and phenolic compounds that can be enhanced by applying ultraviolet light (UV). Here, the effect of UVA or UVB radiation on glucosinolate and phenolic profiles was assessed in broccoli sprouts. Sprouts were exposed for 120 min to low intensity and high intensity UVA (UVAL, UVAH) or UVB (UVBL, UVBH) with UV intensity values of 3.16, 4.05, 2.28 and 3.34 W/m2, respectively. Harvest occurred 2 or 24 h post-treatment; and methanol/water or ethanol/water (70%, v/v) extracts were prepared. Seven glucosinolates and 22 phenolics were identified. Ethanol extracts showed higher levels of certain glucosinolates such as glucoraphanin, whereas methanol extracts showed slight higher levels of phenolics. The highest glucosinolate accumulation occurred 24 h after UVBH treatment, increasing 4-methoxy-glucobrassicin, glucobrassicin and glucoraphanin by ~170, 78 and 73%, respectively. Furthermore, UVAL radiation and harvest 2 h afterwards accumulated gallic acid hexoside I (~14%), 4-O-caffeoylquinic acid (~42%), gallic acid derivative (~48%) and 1-sinapoyl-2,2-diferulolyl-gentiobiose (~61%). Increases in sinapoyl malate (~12%), gallotannic acid (~48%) and 5-sinapoyl-quinic acid (~121%) were observed with UVBH Results indicate that UV-irradiated broccoli sprouts could be exploited as a functional food for fresh consumption or as a source of bioactive phytochemicals with potential industrial applications.

Schinus terebinthifolius: phenolic constituents and in vitro antioxidant, antiproliferative and in vivo anti-inflammatory activities

Schinus terebinthifolius Raddi, Anacardiaceae, native to Brazil, is referred to as “pimento-rosa” and is used to treat inflammatory disease in folk medicine. Studies have reported important pharmacological properties, but these effects have still not been fully exploited. This study reports that the crude extract and isolated compounds of S. terebinthifolius (leaves) have in vitro antioxidant, antiproliferative, and in vivo anti-inflammatory activities. The samples were evaluated for antioxidant activity using 2, 2-diphenyl-1-picrylhydrazyl, β-carotene/linoleic acid and 2,2′-azino-bis-(3-ethylbenzothiazoline)-6-sulphonic acid reagents. The anti-inflammatory effects were assayed against a carrageenan-induced paw oedema model in mice to test doses of 10, 100 and 300mg/kg at different time points in addition to myeloperoxidase activity analysis. The antiproliferative activity was evaluated using ten human tumour cell lines. Two derivatives of gallic acid and four flavonoids were isolated and exhibited considerable antioxidant activity. The extract and its compounds showed selectivity towards ovarian cancer cells, with growth inhibitory activity values ranging from 1.9 to 6.5μg/ml. Sample extracts and methyl gallate significantly inhibited carrageenan-induced oedema in the mice paw oedema experimental model. The calculated topological polar surface area for methyl gallate (86.98Å2) showed good intestinal absorption. The effects reported herein are be related to the presence of flavonoids and the galloyl phenolic derivative content.

Evaluation of cytotoxic, apoptotic, mutagenic, and chemopreventive activities of semi-synthetic esters of gallic acid

Gallic acid and its derivatives are phenolic compounds widely used as food supplements in the form of capsules, liquid extracts, and ointments owing to their good antioxidant properties. Besides, these compounds are potent inhibitors of fungi, bacteria, and some viruses and possess strong antiproliferative and chemopreventive activities. However, gallic acid derivatives are also known to exert harmful effects like mutagenicity and cytotoxicity. The present study aimed to understand and explore the toxicological risks of these compounds. For this, a series of alkyl gallates with side chains varying from five to eight carbons (pentyl, hexyl, heptyl, and octyl gallates) were evaluated for their cytotoxic and pro-apoptotic potential. In addition, the genotoxic effects of alkyl gallates were measured in HepG2 cells using the single cell gel electrophoresis (SCGE)/comet assay and the cytokinesis-blocked micronucleus (CBMN) test. In both the tests, the substances did not induce any significant differences when compared to the control group. In addition, alkyl gallates exhibited a chemopreventive effect, thereby considerably reducing the mutagenicity caused by H2O2. In conclusion, our results suggest that alkyl gallates are non-genotoxic, non-mutagenic, and pro-apoptotic agents, which may serve as suitable and promising candidates for preventing chemically-induced chromosomal damage.

Synthesis and Self-Assembly of Shape Amphiphiles Based on POSS-Dendron Conjugates

Shape has been increasingly recognized as an important factor for self-assembly. In this paper, a series of shape amphiphiles have been built by linking polyhedral oligomeric silsesquioxane (POSS) and a dendron via linkers of different lengths. Three conjugates of octahedral silsesquioxanes (T8-POSS) and dendron are designed and synthesized and are referred to as isobutyl T8-POSS gallic acid derivatives (BPOSS-GAD-1, BPOSS-GAD-2, BPOSS-GAD-3). These samples have been fully characterized by 1H-NMR, 13C-NMR, Fourier transform infrared (FT-IR) spectroscopy and matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry to establish their chemical identity and purity. Driven by different interactions between POSS and dendron, ordered superstructure can be found upon self-assembly. The stabilities and structures of these samples are further studied by using differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), wide-angle X-ray diffraction (WAXD), and molecular simulations. The results show that their melting points range from 74 °C to 143 °C and the molecular packing schemes in the assemblies can form lamellar structure of BPOSS-GAD-3 as determined by the different linkers.

Comparative Evaluation of Phenolic Profile, Antioxidative and Cytotoxic Activities of Different Geranium Species.

Cranesbill (Geranium species) are used traditionally as tonic, antidiabetic, antidiarrheal, antihemorrhoidal, diuretic and for the treatment of cough, fever, tonsillitis, urticaria, kidney pain and gastrointestinal ailments. The leaves of some Geranium species are consumed in traditional Turkish cousin as salad or added to pastry. In the present study, different extracts from G. psilostemon and G. stepporum of the plants were prepared and their SO, NO and ABTS radical scavenging activites were tested. Also, cytotoxic activities of extracts against KB human epidermoid carcinoma cell line tested by MTT method. While EtOAc extracts showed strong radical scavenging activity against SO, NO and ABTS radicals (IC50 of EtOAc extracts of G. psilostemon 29.4, 98.4, µg/ml for SO and NO respectively and TEAC value 0.371 ± 0.29 µM TE) cytotoxic activity against KB cell line was observed for the water extracts of tested species. In order to evaluate phytochemical content of the species; total phenolic, total flavonoid and total flavonol contents of the extracts were estimated and major compounds of the extracts were determined as gallic acid, methyl gallate and pusilagin using HPLC-DAD system. Taken together, the results showed that gallic acid derivatives are important for the bioactivities of Geranium species, and it may be promising possible sources for future novel antioxidants in food and pharmaceutical formulations.

Shushe Acids A-D from Ganoderma Applanatum

Ganoderma applanatum is a fungus used for the prevention and treatment of a variety of disorders in China. In the present study, four new compounds, named shushe acids A-D (1-4), were isolated from the fruiting bodies of this species. Their structures were identified on the basis of spectroscopic methods. Compounds 1-4 are all natural product hybrids composed of derivatives of gallic acid, glycerol and succinic acid. None of the four compounds showed activity against the MCF-7 cell line.

Anti-oxidative, acetylcholinesterase and pancreatic lipase inhibitory activities of compounds from Dasiphora fruticosa, Myricaria alopecuroides and Sedum hybridum

Total of 35 phenolics and flavonols were isolated from flowers and leaves of Dasiphora fruticosa Rydb., from branches of Myricaria alopecuroides Schrenk. and from the herb of Sedum hybridum L. The isolated compounds were identified on the basis of spectral data and tested for their anti-oxidative, acetylcholinesterase and pancreatic lipase inhibitory activities.Quercetin glycosides, gallic acid, (-)EGCG and gossypetin-8-O-xylopyranoside tellimagrandin II exhibited strong anti-oxidative activity by the DPPH scavenging method. The acetylcholinesterase inhibitory activity of quercetin glycosides and (-)EGCG was higher than those of other compounds. Whereas, tellimagrandin II, (-)EGCG and gallic acid derivatives exhibited the most potent inhibitory activity against the pancreatic lipase enzyme among the isolated compounds. Only (-)EGCG showed a prominent activity against all assayed experiments. It was concluded that these plants could be studied further for their potential as anti-oxidative, anti-aging and lipid lowering active products.

DESIGN AND SCREENING OF GALLIC ACID DERIVATIVES AS INHIBITORS OF MALARIAL DIHYDROFOLATE REDUCTASE (DHFR) BY IN SILICO DOCKING

Objective: Malaria is an infection disease caused by plasmodium parasite with high prevalence in tropic and subtropic countries. The aim of this work was to design and screening of gallic acid derivatives as inhibitors of malarial dihydrofolate reductase (DHFR) by in silico docking.Methods: The derivatives were designed by expanding the carboxyl group of gallic acid with open-chain moiety of L-threonine-allyl esters, as well as to modify the hydroxy groups on the aromatic ring of gallic acid with methoxyl group in the derivatives. In silico approach has been utilized in finding the potential antimalaria of gallic acid derivatives. Fourteen Gallic acid derivatives (compound 2-15) were modeled into 3D structures by ACD Labs software. Geometry optimization and minimization of energy 3D structure of gallic acid derivatives as ligands using the MOE software. Docking process and amino acid analysis were executed by using MOE software. Results: In silico docking study resulted in the three top-ranked compounds, namely compound 5, 8 and 12. Among those three top-ranked compounds, compound 12 (octyl gallate), exhibited the strongest interaction and greatest inhibitory activity against the receptor of malarial DHFR.Conclusion Our results clearly demonstrated that compound 12 (octyl gallate) could be developed as a promising candidate for the new anti-malarial agent.

Ulcer Prevention Effect Of 3,4,5-Tihydroxy-N0-[(2-Methyl-1H-Indol-3yl)Methylidene]Benzohydrazide In HCl/Ethanol-Induced Gastric Mucosal Damage In Rats.

The newly synthesized, 3,4,5-Trihydroxy-N 0-[(2-methyl-1H-indol-3-yl)-methylidene] benzohydrazide (TIBH), is an indole and gallic acid derivative. The aim of this research investigation was to evaluate the acute toxicity and the ulcer prevention potential of TIBH in HCl/Ethanol-induced gastric ulcer rat model. Six groups of rats were orally received 5ml/kg of vehicle (1 % Carboxy methyl cellulose) for the normal and ulcer control groups each, Omeprazole (20mg/kg) for positive control, 50 mg/kg, 100 mg/kg and 200 mg/kg of TIBH for experimental groups, respectively. After one hour, instead of rats in the normal group which received 5ml/kg of 1% CMC, other groups received 5ml/kg of HCl/Ethanol. All rats were sacrificed after one additional hour. Gastric juice, gastric mucosa, morphologies of gastric ulcers and protein expressions of both control and treatment groups were evaluated. TIBH showed a ulcer prevention potential by increase of the mucus secretion, decrease of the gastric acidity, up-regulation of HSP70 protein, down-regulation of Bax protein, decrease of the lipid peroxidation and the increase of the Superoxide dismutase (SOD) activity in gastric tissue homogenate. Acute toxicity assay exposed valuable information on the safety of this compound. TIBH had a dose dependent ulcer prevention potential against HCl/Ethanol-triggered gastric ulcer.

Total Synthesis of Ellagitannins via Sequential Site-Selective Functionalization of Unprotected D-Glucose.

A short-step total synthesis of the natural glycosides pterocarinin C and tellimagrandin II (eugeniin) has been performed by sequential and site-selective functionalization of free hydroxy groups of unprotected D-glucose. The key reactions are β-selective glycosidation of a gallic acid derivative using unprotected D-glucose as a glycosyl donor and catalyst-controlled site-selective introduction of a galloyl group into the inherently less reactive hydroxy group of the glucoside.

IN SILICO MOLECULAR DOCKING AND PHARMACOKINETIC PREDICTION OF GALLIC ACID DERIVATIVES AS PPAR-γ AGONISTS

<p><strong>Objective: </strong>To perform molecular docking and pharmacokinetic prediction of gallic acid derivatives as Peroxisome proliferator-activated receptors-γ (PPAR-γ) agonist for the treatment of diabetes.</p><p><strong>Methods: </strong>Molecular docking study on gallic acid and different derivatives of gallic acid was performed using GOLD v5.2 software. In addition to this, all the derivatives were analysed for drug likeliness, Lipinski’s rule and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties using online tools like admet SAR, Molinspiration and Medchem designer.</p><p><strong>Results: </strong>Molecular docking studies reveals that SSP-12, SSP-13 and SSP-40 demonstrated significant binding to the PPAR-γ receptor with good Gold score fitness (73.11, 69.86 and 75.51 respectively) and relative ligand energy (-8.26,-8.33 and-7.82, respectively) as compared to standard drugs i.e. rosiglitazone and pioglitazone, (64.10 and 66.72) and (-4.30 and-2.47) respectively.</p><p><strong>Conclusion: </strong>The final results of molecular docking along with information gathered from pharmacokinetic parameters of gallic acid derivatives may be utilised further for the development of newer PPAR-γ agonists having anti-diabetic potential with better pharmacokinetic and pharmacodynamic profile.</p>

Antioxidative Activity of Gallic Acid Derivatives

Antioxidative Activity of Gallic Acid Derivatives

P2-142 - Cytotoxic Effects of Gallic Acid Derivatives on Hormone Dependent Breast Cancer MCF-7

P2-142 - Cytotoxic Effects of Gallic Acid Derivatives on Hormone Dependent Breast Cancer MCF-7

Thermal and mechanical properties of bio-based polymer networks by thiol-ene photopolymerizations of gallic acid and pyrogallol derivatives

Allylated pyrogallol (A3PG) and acrylated pyrogallol (Ac3PG) as bio-based trienes, and allylated gallic acid (A4GA) and acrylated allyl gallate (Ac3A1GA) as bio-based tetraenes were synthesized from pyrogallol and gallic acid, respectively. Thiol-ene photopolymerizations of the bio-based polyenes and a pentaerythritol-based primary tetrathiol (pS4P) at the allyl/SH ratio of 1/1 produced photo-cured resins (A3PG-pS4P, Ac3PG-pS4P, A4GA-pS4P and Ac3A1GA-pS4P). The FT-IR spectral analysis revealed that thiol-ene reactions of thiol/allyl and thiol/acryloyl groups smoothly proceeded. Gel fractions of acryl-based cured resins were a little higher than those of allyl-based cured resins. The swelling test and dynamic mechanical analysis revealed that GA- and acryl-based cured resins exhibited higher crosslinking densities than PG- and allyl-based cured resins, respectively. A higher order of tan δ peak temperature was Ac3PG-pS4P (48.3 ° C) > Ac3A1GA-pS4P (24.1 ° C) > A4GA-pS4P (22.1 ° C) > A3PG-pS4P (−7.8 ° C). Ac3PG-pS4P displayed the highest 5 % weight loss temperature, tensile strength and tensile modulus among all of the cured resins.

Mutagenicity assessment of propyl propane thiosulfinate: An organosulfur compound derived from Allium sp.

Davilla nitida and Davilla elliptica (Dilleniaceae) are plants that occur predominantly in the cerrado region of South America. They are used in popular medicine to treat stomach diseases, diarrhea and swelling, particularly of the lymph nodes and testicles. Chemical investigation of these two plant species led to the identification of the compounds myricetin-3-O-α-l-rhamnoside (myricitrin), quercetin-3-O-α-l-rhamnoside (quercitrin), myricetin, quercetin and gallic acid derivatives in the leaves of D. nitida and D. elliptica. Therefore, it was concluded that the two species of Davilla possess qualitatively similar chemical profiles. In the present study, the mutagenic and genotoxic potential of these plants and of their isolated compounds was tested in the Salmonella typhimurium assay (Ames test) with strains TA100, TA98, TA102 and TA97a, in the micronucleus test with peripheral blood cells of mice treated in vivo, and in plasmid DNA to analyze DNA strand-breaks. In the assessment of mutagenic potential by the Ames test, extracts from both plant species and a D. nitida ethyl-acetate fraction induced positive responses. On the other hand, none of the extracts showed genotoxic activity in the mouse cells. In the presence of metal ion, D. nitida and D. elliptica aqueous and ethyl-acetate fractions, as well as their isolated compounds, induced single- and double-strand-breaks in plasmid DNA in a cell-free system.

Quantitative determination of a synthetic amide derivative of gallic acid, SG-HQ2, using liquid chromatography tandem mass spectrometry, and its pharmacokinetics in rats

An amide derivative of gallic acid (GA), 3,4,5-trihydroxy-N-(8-hydroxyquinolin-2-yl)benzamide) (SG-HQ2) was recently synthesized, and its inhibitory actions were previously shown on histamine release and pro-inflammatory cytokine expression. In this study, a simultaneous quantification method was developed for the determination of SG-HQ2 and its possible metabolite, GA, in rat plasma using liquid chromatography with a tandem mass spectrometry (LC–MS/MS). After simple protein precipitation with acetonitrile including diclofenac (internal standard, IS), the analytes were chromatographed on a reversed phased column with a mobile phase of acetonitrile and water (60:40, v/v, including 0.1% formic acid). The ion transitions of the precursor to the product ion were principally protonated ion [M+H]+ at m/z 313.2→160.6 for SG-HQ2, and deprotonated ions [M−H]− at m/z 168.7→124.9 for GA and 296.0→251.6 for the IS. The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods.This method was successfully applied to a pharmacokinetic study of SG-HQ2 after intravenous administration in rats.

Phenolic composition and antioxidant capacity of Ugni molinae Turcz. leaves of different genotypes

Ugni molinae Turcz. is a native shrub of Chile, known for its edible berries and its leaves, which have been the focus of recent attention, as a good source of phenolic compounds to be used in cosmetics and food products. The aim of this study was to assess the differences in the phenolic composition and antioxidant capacity of the ethanolic extracts from the leaves of 10 genotypes of U. molinae, that were cultivated under the same soil, climate and agronomical management. Antioxidant activity was assessed by complementary methods (ORAC-Fl, FRAP and DPPH assay), phenolic composition of each extract was analyzed by LC–MS. Phenolic and flavonoid total contents were determined by Folin-Ciocalteu and AlCl3 methods. Significative differences were found by these methods, and ellagitannins, gallic acid derivatives and flavonols were identified as responsible for these differences, showing the influence of the genotype on the phenolic composition of U. molinae leaves.

Methyl gallate, a potent antioxidant inhibits mouse and human adipocyte differentiation and oxidative stress in adipocytes through impairment of mitotic clonal expansion.

Methyl gallate (MG) is a derivative of gallic acid and a potent antioxidant. In this study, we confirmed that MG treatment effectively inhibits lipid accumulation, which occurred mostly in the early stages of adipogenesis. We also showed that shortly after adipogenic induction, MG facilitated a G0/G1 cell cycle arrest. Mechanistic studies revealed that MG treatment inhibited ERK1/2 phosphorylation, which is a key regulator of the G1- to S-phase transition. Furthermore, MG treatment prevented the adipogenic hormonal stimuli-induced inhibition of the cyclin-dependent kinase inhibitor p27Kip1 . This led to inhibition of the transcription factor E2F1 by preventing the phosphorylation of, and thereby activation of its destruction partner RB. MG treatment also downregulated factors that are upstream of RB-E2F1 signaling such as Cdk2, Cyclin E, Cdk4, and Cyclin D1 where Cyclin D3 level was unaffected. We also found that MG treatment markedly decreased the expression and phosphorylation of C/EBPβ, by phosphorylating, and therefore inactivating, GSK3β, which is a prerequisite for its DNA binding capacity, and thereby mitotic clonal expansion (MCE). Ultimately, MG treatment downregulates key terminal adipogenic transcription factors including C/EBPα, PPARγ, aP2 (Fabp4), and adiponectin. Moreover, MG also protects adipocytes from oxidative stress by alleviating intracellular reactive oxygen species and activating Nrf2, HO-1, and PRDX3. Thus, this study provides a mechanistic insight into the anti-adipogenic actions of MG. © 2016 BioFactors, 42(6):716-726, 2016.

Gallic Acid Derivatives (GADs) from Loranthus micranthus Linn. Parasitic on Hevea brasiliensis with Antioxidative Capacity

Semi-preparative High Liquid Column Chromatographic separation of the ethyl acetate soluble fraction of a methanol extract of the leaves of Loranthus micranthus Linn. parasitic on Hevea brasiliensis (Willd. ex A. Juss.) led to the isolation of two gallic acid derivatives (1-2). The structures of the compounds were solved by using spectroscopic methods (1D and 2D NMR and mass spectroscopic data) as well as by comparison with literature values. The compounds were identified as 3,4,5-tri-O-methyl gallic acid (1) and methyl 3-O-methyl gallate (2). The antioxidant activity of the isolated compounds was evaluated by using DPPH assay. Compounds 1 and 2 showed strong antioxidative capacity with inhibitory concentration (IC50) values of 10.0 ± 0.03 and 45.0 ± 0.02 ?M, respectively.Dhaka Univ. J. Pharm. Sci. 14(2): 139-145, 2015 (December)

Anti-ulcer mechanisms of polyphenols extract of Euphorbia umbellata (Pax) Bruyns (Euphorbiaceae)

Ethnopharmacological relevanceEuphorbia umbellata (leitosinha) is used in southern Brazilian folk medicine to treat gastric problems, as well as for its analgesic and anti-inflammatory properties. Aim of studyTo evaluate the anti-ulcer effects of methanolic bark fraction (MF) against in vivo and in vitro assays, as well as an antioxidant, antibacterial and chromatographic study of this fraction. Materials and methodsIn vivo anti-ulcer activity was performed using ethanol and indomethacin models with different MF concentrations (50, 100 or 200mg/Kg). The stomachs of the animals were applied to histological evaluation, and the serum to evaluate the ABTS•+ radical capture. The 200mg/Kg dose was used to analyze the mechanisms involved in antiulcerogenic properties of methanolic fraction. The in vitro activity was performed using several different antioxidant assays, in addition to anti-Helicobacter pylori and anti-urease experiments. The chromatographic study was carried out by LC-MS analysis. ResultsPharmacological investigation of the MF showed an anti-ulcer potential in ethanol and indomethacin in vivo assays. The material presented a high antioxidant activity for several oxidant in vitro systems (DPPH•, ABTS•+, O2•-, HOCl, TauCl and HRP), as well as an ABTS•+ capture increasing (7.5%) by the treated animals serum (when compared to the negative control). Prostaglandins, nitric oxide/ cyclic guanosine monophosphate pathway and involvement of the protein components of the glutathione complex are some of the mechanisms related with this potential anti-ulcer action. The histological examination of the stomachs of the animals showed that the MF also prevents local action of offensive agents. Chemical analysis using LC-QTOF-MS revealed the presence of ellagic and gallic acid derivatives and flavonols. ConclusionThe findings provide scientific basis to the ethnopharmacological purpose of the studied plant and the biological activities of MF of E. umbellata stem bark may be due to the presence of phenolic compounds.