Gallic Acid Derivatives Research Articles

Molecular docking studies of some selected gallic acid derivatives against five non-structural proteins of novel coronavirus

BackgroundThe World Health Organization has recently declared a new coronavirus disease (COVID-19) a pandemic and a global health emergency. The pressure to produce drugs and vaccines against the ongoing pandemic has resulted in the use of some drugs such as azithromycin, chloroquine (sulfate and phosphate), hydroxychloroquine, dexamethasone, favipiravir, remdesivir, ribavirin, ivermectin, and lopinavir/ritonavir. However, reports from some of the clinical trials with these drugs have proved detrimental on some COVID-19 infected patients with side effects more of which cardiomyopathy, cardiotoxicity, nephrotoxicity, macular retinopathy, and hepatotoxicity have been recently reported. Realizing the need for potent and harmless therapeutic compounds to combat COVID-19, we attempted in this study to find promising therapeutic compounds against the imminent threat of this virus. In this current study, 16 derivatives of gallic acid were docked against five selected non-structural proteins of SARS-COV-2 known to be a good target for finding small molecule inhibitors against the virus, namely, nsp3, nsp5, nsp12, nsp13, and nsp14. All the protein crystal structures and 3D structures of the small molecules (16 gallic acid derivatives and 3 control drugs) were retrieved from the Protein database (PDB) and PubChem server respectively. The compounds with lower binding energy than the control drugs were selected and subjected to pharmacokinetics screening using AdmetSAR server. Results4-O-(6-galloylglucoside) gave binding energy values of − 8.4, − 6.8, − 8.9, − 9.1, and − 7.5 kcal/mol against Mpro, nsp3, nsp12, nsp13, and nsp15 respectively. Based on the ADMET profile, 4-O-(6-galloylglucoside) was found to be metabolized by the liver and has a very high plasma protein binding. ConclusionThe result of this study revealed that 4-O-(6-galloylglucoside) could be a promising inhibitor against these SAR-Cov-2 proteins. However, there is still a need for further molecular dynamic simulation, in vivo and in vitro studies to support these findings.

Inhibition of the intestinal postprandial glucose transport by gallic acid and gallic acid derivatives.

Inhibition of glucose uptake in the intestine through sodium-dependent glucose transporter 1 (SGLT1) or glucose transporter 2 (GLUT2) may be beneficial in controlling postprandial blood glucose levels. Gallic acid and ten of its derivatives were identified in the active fractions of Terminalia chebula Retz. fructus immaturus, a popular edible plant fruit which has previously been associated with the inhibition of glucose uptake. Gallic acid derivatives (methyl gallate, ethyl gallate, pentyl gallate, 3,4,6-tri-O-galloyl-β-d-glucose, and corilagin) showed good glucose transport inhibition with inhibitory rates of 72.1 ± 1.6%, 71.5 ± 1.4%, 79.9 ± 1.2%, 44.7 ± 1.2%, and 75.0 ± 0.7% at 5 mM d-glucose and/or 56.3 ± 2.3, 52.1 ± 3.2%, 70.2 ± 1.7%, 15.6 ± 1.6%, and 37.1 ± 0.8% at 25 mM d-glucose. However, only 3,4,6-tri-O-galloyl-β-d-glucose and corilagin were confirmed GLUT2-specific inhibitors. Whilst some tea flavonoids demonstrated minimal glucose transport inhibition, their gallic acid derivatives strongly inhibited transport effect with GLUT2 specificity. This suggests that gallic acid structures are crucial for glucose transport inhibition. Plants, such as T. chebula, which contain high levels of gallic acid and its derivatives, show promise as natural functional ingredients for inclusion in foods and drinks designed to control postprandial glucose levels.

Gallic Acid Derivative Stimulate Osteogenic Differentiation by Regulating Autophagy via JNK/mTOR Signaling Pathways in vitro

This paper was to demonstrate the effects and mechanism of methylated-based gallates 4-O-methylgallic acid on osteoblast differentiation. Cells were treated with different concentrations of 4-O-methylgallic acid.Then researchers evaluated the overall effects of 4-O-methylgallic acid on osteoblast by cell proliferation bioassay, ALP activity assay, Alizarin red S staining and detection the expression level of osteogenic-related gene including runt-related transcription factor 2 (RUNX2), bone sialoprotein (BSP), osteocalcin (OCN), alpha-1 type I collagen (COL1A1).Subsequently, cells were treated with ZXHA-TC with or without the JNK inhibitor SP600125 and the autophagy inhibitor 3-methyladenine (3-MA).Then western blotting and cell transfection were used by two researchers explore the potential relationship and signaling pathway between autophagy and the differentiation of osteoblast mediated by 4-O-methylgallic acid.The results of the present study demonstrated that 4-O-methylgallic acid stimulated cell viability, increased ALP activity, upregulated the expression of osteogenic genes, evoked the expression of autophagy markers. A range of 6.25x10-3μg/ml to 6.25x10-1μg/ml were recommended, within which 6.25x10-2μg/ml showed the best performance. SP600125 and 3-methyladenine suppressed the stimulating effects of 4-O-methylgallic acid on osteogenic differentiation By blocking JNK/mTOR signaling pathway.This study indicated that 4-O-methyl gallic acid stimulated osteoblast differentiation by regulating autophagy via JNK/mTOR signaling pathways.

A Polyphenol-Rich Extract From Entada abyssinica Reduces Oxidative Damage in Cryopreserved Ram Semen.

The Splinter bean, Entada abyssinica, is widely used in folk medicine. In the current work, we profiled the secondary metabolites from E. abyssinica bark extract using LC-MS and investigated its effect on cryopreserved ram semen. Twenty-eight compounds, including tannins and gallic acid derivatives that prevailed in the extract, were tentatively identified. Results showed that the quality of the post-thawed semen showed a significant improvement when the extract was added to the extender at a concentration of 375 μg/mL. The progressive motility and plasma membrane integrity of sperm cells were significantly increased in the post-thawed semen; however, the total antioxidant capacity (TAC) was insignificantly increased. A significant decrease in the concentration of hydrogen peroxide was detected as well. No significant changes were observed in activities of lactate dehydrogenase (LDH), alanine aminotransaminase (ALT), and aspartate transaminase (AST) within the treated samples. Intact sperm percentage was significantly increased, while apoptotic and necrotic sperm percentages were reduced significantly. Molecular docking of some individual components from the extract revealed their potential to interfere with the apoptosis cascade in which Bcl-2 is involved. In conclusion, Entada abyssinica appears to be useful for cryopreservation presumably owing to its polyphenol content that has potent antioxidant capacity scavenging reactive oxygen species (ROS), enhancing the endogenous antioxidant system and inhibiting lipid peroxidation.

Hepatoprotective Activity of Bergenin against Xenobiotics-Induced Oxidative Stress in Human Hepatoma (HepG2) Cells

Bergenin, a natural derivative of gallic acid, has been shown to exert anti-oxidant and anti-inflammatory activities. This study aimed to determine hepatoprotective activity of bergenin against ethanol and tert-butyl hydroperoxide (TBHP) induced oxidative stress in human hepatoma (HepG2) cells. HepG2 cells (5x105 cells/well) were co-treated with ethanol (100 mM) or TBHP (100 µM) and either bergenin (75, 150, and 300 µM) or gallic acid (60 µM, positive control) for 24 h. Cell viability, hematoxylin and eosin staining of cell morphology, cellular injury biomarkers: lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA), and antioxidant biomarkers: superoxide dismutase (SOD), catalase (CAT), and total glutathione (GSH) content, were determined. Ethanol and TBHP decreased cell viability (86.67% and 84.49% of control, respectively), increased LDH toxicity (12.53% and 15.91% of control, respectively), and increased AST, ALT, and MDA levels, compared with the control. Based on cell morphology, both ethanol and TBHP injured HepG2 cells causing the loss of cell nuclei. Treatment of HepG2 cells with either ethanol or TBHP reduced SOD and CAT activities and depleted total GSH content, compared with the control. Bergenin and gallic acid improved the cell morphology, elevated cell viability (95.94-99.20% and 97.72-99.62% of control, respectively), lowered LDH toxicity (8.14-9.10% and 7.82-8.92% of control, respectively), restored AST, ALT, and MDA levels, promoted SOD and CAT activities, and enhanced the total GSH content of ethanol- and TBHP-treated HepG2 cells. Bergenin exhibited hepatoprotective activity via restoration of the oxidant-antioxidant system and is a potential candidate for hepatoprotective treatment.

Chromatographic Separation of Breynia retusa (Dennst.) Alston Bark, Fruit and Leaf Constituents from Bioactive Extracts.

Breynia retusa (Dennst.) Alston (also known as Cup Saucer plant) is a food plant with wide applications in traditional medicine, particularly in Ayurveda. Extracts obtained with four solvents (dichloromethane, methanol, ethyl acetate and water), from three plant parts, (fruit, leaf and bark) were obtained. Extracts were tested for total phenolic, flavonoid content and antioxidant activities using a battery of assays including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), cupric reducing antioxidant capacity (CUPRAC), total antioxidant capacity (TAC) (phosphomolybdenum) and metal chelating. Enzyme inhibitory effects were investigated using acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase and α-glucosidase as target enzymes. Results showed that the methanolic bark extract exhibited significant radical scavenging activity (DPPH: 202.09 ± 0.15; ABTS: 490.12 ± 0.18 mg Trolox equivalent (TE)/g), reducing potential (FRAP: 325.86 ± 4.36: CUPRAC: 661.82 ± 0.40 mg TE/g) and possessed the highest TAC (3.33 ± 0.13 mmol TE/g). The methanolic extracts were subjected to LC-DAD-MSn and NMR analysis. A two-column LC method was developed to separate constituents, allowing to identify and quantify forty-four and fifteen constituents in bark and fruits, respectively. Main compound in bark was epicatechin-3-O-sulphate and isolation of compound was performed to confirm its identity. Bark extract contained catechins, procyanidins, gallic acid derivatives and the sulfur containing spiroketal named breynins. Aerial parts mostly contained flavonoid glycosides. Considering the bioassays, the methanolic bark extract resulted a potent tyrosinase (152.79 ± 0.27 mg kojic acid equivalent/g), α-amylase (0.99 ± 0.01 mmol acarbose equivalent ACAE/g) and α-glucosidase (2.16 ± 0.01 mmol ACAE/g) inhibitor. In conclusion, methanol is able to extract the efficiently the phytoconstituents of B. retusa and the bark is the most valuable source of compounds.

A novel “on-off-on” acylhydrazone-based fluorescent chemosensor for ultrasensitive detection of Pd2+

A novel acylhydrazone-based fluorescent sensor G has been successfully synthesized to achieve ultrasensitive detection of Pd2+ in water. Compound G is composed of gallic acid derivatives and biphenyl by acylhydrazone group, which formed a suspension and promote intermolecular self-assembly in DMF by π-π stacking, van der Waals forces and intermolecular hydrogen bonds, leading to the formation of stable supramolecular organogels OG in DMF by the gel factor G. And the supramolecular organogels OG realized ultra-sensitive detection of Pd2+ in water via fluorescence quenching at 475 nm. The LOD for Pd2+ for the chemosensor G is 2.03 × 10−8 M and the resulting metal gel PdG can also recognize H2OP4− among the various anions by fluorescence spectroscopy. And the sensing mechanism of chemosensor G and metal ions has been studied through a series of characterization methods including FE-SEM, FT-IR, XRD, 1H NMR titrations and XPS, with the results indicating that the π-π stacking and hydrogen bond were broken during the addition of the cation.

ISOLATION AND CHARACTERISATION OF BERGENIN FROM ETHYL ACETATE EXTRACT OF FLUEGGEA VIROSA LEAVES

Bergenin is an important constituent of Flueggea virosa (Euphorbiaceae), a tropical plant with several traditional uses. While there are numerous reports on the isolation and characterization of bergenin, a rapid, high-throughput, readily accessible method for the isolation and characterization of the compound locally has not been reported. Isocratic elution of ethyl acetate extract via vacuum liquid chromatography (VLC) with methanol produced a white amorphous solid (100 mg), which was successfully isolated from 250 g of the plant. On the basis of spectral data (1H, C NMR, COSY, HSQC and HMBC) and comparison with literature reports, the structure of this solid was shown to be bergenin, a dihydroisocoumarin derivative of glucopyranosyl gallic acid.

Microwave-assisted extraction of phenolic compounds with antioxidant and anti-proliferative activities from supercritical CO2 pre-extracted mango peel as valorization strategy

This work includes the second/sequential stage of a green-based valorization strategy of mango peel. An exhausted biomass from a pilot-scale CO2 supercritical extraction process was reused for obtaining phenolic-rich extracts with high antioxidant and anti-proliferative activity, employing microwave-assisted extraction. The effects of microwave power (400–800 W), liquid-to-solid ratio (10–50 mL/g) and extraction time (60–120 s) on process yield, phenolic content, and antioxidant capacity were investigated using a Box-Behnken design. A solution consisting of 60% aqueous ethanol was used as extraction solvent. The results showed that microwave power and liquid-to-solid ratio were the most influential factors on the responses variables. The highest total phenolic content (52.08 mg gallic acid eq./g d. w.) and antioxidant activities (2.75 mmol trolox eq./g extract, and of 6.47 μg/mL expressed in DPPH, EC50) were obtained at 800 W, 50 g/mL, and 90 s. Mango peel extract recovered at optimal conditions provided high anti-proliferative activity against HT-29 colon cancer cells line, after 24 h treatment (IC50 = 22.98 μg/mL). Gallic acid derivatives, such as galloyl-esters, xanthones like mangiferin, flavonoids, including quercetin and quercetin glycosides were tentatively identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Most probably, the compounds responsible for the outstanding anti-proliferative activity.

Cuphea calophylla var. mesostemon (Koehne) S.A. Graham: A Whole-Ethnopharmacological Investigation.

Several species of Cuphea are used medicinally and are reported to have cardioprotective, diuretic, and antihypertensive properties. In Brazil, Cuphea species are collectively called "sete-sangrias" due to their similar appearances and are also used interchangeably for the same therapeutic purposes. So the aim of the study was to characterize morphoanatomy of leaves and stems, evaluate the safety, and investigate the diuretic, hypotensive, vasodilatory, and antioxidant properties of ethanol-soluble fraction of Cuphea calophylla var. mesostemon (Koehne) S.A. Graham. Initially, the morphoanatomical characterization of the leaves and stems of C. calophylla var. mesostemon was performed. For the pharmacological evaluation, the ethanol-soluble fraction from Cuphea calophylla (ESCC) was obtained and chemically characterized by high-performance liquid chromatography coupled with a diode array detector and tandem mass spectrometry techniques. Then, acute toxicity, diuretic, hypotensive, antioxidant, and vasodilatory effects were evaluated in Wistar rats. The main chemical compounds identified from ESCC were gallic acid derivatives, ellagitannins, and flavonoids. ESCC showed no acute toxic effect. ESCC showed no acute toxic effect and the estimated median lethal dose (LD50) was above 2000 mg/kg. ESCC treatment (30, 100, and 300 mg/kg) did not present any significant acute diuretic or hypotensive effects. However, an important reduction in the elimination of electrolytes was observed after the acute administration, and a significant increase in renal sodium elimination was observed after 7 days of treatment. In the cardiac tissue, the groups treated with ESCC presented significant increase in superoxide dismutase activity.

Phytochemical Components and Bioactivity Assessment among Twelve Strawberry (Arbutus unedo L.) Genotypes Growing in Morocco Using Chemometrics.

There are not many exhaustive works emphasizing the amount of genetic diversity among the strawberry tree (Arbutus unedo L.) genotypes in Morocco. This work aims to assess the biochemical composition of strawberry tree fruits, as well as to establish the variation of this composition among them. In this study, total phenols (TP), total flavonoids (TF), condensed tannins (CT) and hydrolyzable tannins (HT), total anthocyanins (TA), and free radical scavenging activity through ABTS were investigated in strawberry tree fruits. Furthermore, qualitative and quantitative analyses of individual phenolic compounds by high-performance liquid chromatography (HPLC) were carried out. Color parameters such as lightness (L*), Chroma (c*), and hue angle (h°) were also investigated. All studied variables showed highly significant differences among all samples with the exception of hydrolyzable tannins and chromatic coordinates. TP varied from 22.63 ± 1.74 to 39.06 ± 2.44 mg GAE/g DW, TF varied from 3.30 ± 0.60 to 8.62 ± 1.10 mg RE/g DW, and TA ranged between 0.12 ± 0.06 and 0.66 ± 0.15 mg cya-3-glu/100 g DW. In addition, CT and HT amounts were in the range of 10.41 ± 1.07–16.08 ± 1.50 mg TAE/g DW and 4.08 ± 2.43–6.34 ± 3.47 TAE/g DW, respectively. Moreover, the IC50 value (ABTS) ranged between 1.75 and 19.58 mg AAE/g DW. 17 phenolic compounds were detected in strawberry tree fruits. Gallocatechol and catechin were the most abundant phenolic compounds. Matrix of correlations revealed significant positive and negative correlations among variables particularly c*, a*, and b*. Principal component analysis (PCA) showed that the first three components formed than 68% of the total inertia. The following variables gallic acid, protocatechuic, gallocatechin, gallic acid derivative, chlorogenic acid, syringic acid, ellagic acid derivative II, L*, and h* were the most involved in the total variance explained. Hierarchical clustering classified samples into one main cluster, with a single branch. The results highlight a high biochemical diversity within studied strawberry genotypes, which is probably more genetically related.

Light quality on growth and phenolic compounds accumulation in Moringa oleifera L. grown in vitro

All plant parts of the Moringa oleifera can contain relevant concentrations of phytochemicals with health benefits. Plants grown in vitro allow pathogen-free plant material production and rapid propagation, and this technique is widely used to obtain secondary metabolites. This study analyzed how light spectrum quality affects growth, chlorophyll, and total phenolic content in M. oleifera plants grown in vitro. M. oleifera seeds were inoculated in MS medium supplemented with 3% sucrose and 0.7% agar and were stored under a controlled temperature, humidity and photoperiod. The light conditions tested were white fluorescent lamps (WFL) and light-emitting diodes (LED: 70% red + 30% blue), both standardized with a photon flux density of 58 μmol m-2s-1. Radiation emitted by WFL and LED did not influence stem germination, height, or diameter. However, WFL provided higher total chlorophyll levels. All plant parts germinated in vitro were analyzed via high-performance liquid chromatography with a diode-array detector (HPLC-DAD), and preliminary analyses revealed preferential synthesis of gallic acid derivatives in the leaves under LED radiation. For the total phenolic content, leaves under the LED and WFL irradiations showed 3.524 ± 0.054 and 3.805 ± 0.304 micrograms, respectively, of gallic acid equivalents per milligram of dry matter (μg GAE mg-1 DM). Light quality did not interfere with phenolic compound accumulation; however, it stimulated the preferential synthesis of gallic acid derivatives in leaves grown under LED radiation, and the evidence indicated that all evaluated organs synthesized nonpolar substances.

Changes in phenolic compounds and antioxidant capacity of Andean raspberries in response to Peronospora sparsa

In Colombia, the Andean raspberry (Rubus glaucus Benth) is of large economic significance because of its use in industry and widespread consumption as a fresh fruit. However, this crop is highly susceptible to disease by Peronospora sparsa, a fungus that causes between 50 % and 70 % production loss. Plants respond to pathogen-induced damage by increasing the production of specific secondary metabolites, such as phenolic compounds, which have broad industrial applications. This work estimated the antioxidant capacity and phenolic content of healthy and Peronospora sparsa-infected Andean raspberry fruits. Antioxidant capacity was analyzed by DPPH and FRAP methods, while phenolic compounds were analyzed by high performance liquid chromatography coupled to diode array detection (HPLC-DAD). According to the DPPH method, antioxidant capacity increased from 45.9 ± 1.61 µmol TE g−1 fresh sample in healthy fruits to 67.02 ± 0.58 µmol TE g−1 fresh sample in affected fruits. The FRAP method revealed an antioxidant response difference from 5.19 ± 0.8 mmol TE 100 g−1 fresh sample in healthy fruits vs. 10.97 ± 0.27 mmol TE 100 g−1 fresh sample in affected fruits. The phenolic compound content was observed in a range of 4.14 ± 1.16 to 72.03 ± 26.68 mg GAE L−1 for healthy fruits and from 4.48 ± 1.76 to 221.89 ± 1.18 mg GAE L−1 for affected fruits. Phenolic acids were the main phenols detected, encompassing derivatives of gallic acid, chlorogenic acid, ferulic acid, ellagic acid, and p-coumaric acid. This work confirmed that the Peronospora sparsa-infected berries contained relatively more antioxidants and phenolic acid compounds than their healthy counterparts, and that this difference was likely due to a defense mechanism to cope with pathogen-induced damage.

Insecticidal and antifungal activities of saline extract from Abarema cochliocarpos bark against pests with relevance to human health and agronomy

Abstract During the last decades, there has been an increasing interest in natural compounds for the control of insect pest. The present study evaluated the insecticidal activity of a saline extract of Abarema cochliocarpos bark against Aedes aegypti, Sitophilus zeamais, Nasutitermes corniger, and Fusarium spp. Thin layer chromatography revealed the presence of anthraquinones, saponins, and hydrolyzable and condensed tannins in the extract. High-performance liquid chromatography with a diode-array detector confirmed the presence of gallic acid, catechin, ellagic acid, and catechin derivatives. The presence of lectins and trypsin inhibitor was also confirmed. The extract exhibited insecticidal activity against the fourth-stage larvae of A. aegypti (LC50- 8.22 μg/mL). Furthermore, the extract did not exhibit insecticidal activity against the adults of S. zeamais even 7 d after treatment. However, a strong deterrent effect was observed. The extract promoted the mortality of N. corniger workers and soldiers (LC50: 1.89 and 1.83 mg/mL, respectively). The extract (0.2–0.8 mg/mL) inhibited the mycelial growth of F. oxysporum (69.0%–83.1% inhibition) and F. lateritium (23.0%–59.0% inhibition). These results indicate that the bark of A. cochliocarpos is a source of bioactive agents that are effective against insect and fungal pests.

Metabolomic Changes in Mango Fruit Peel Associated with Chilling Injury Tolerance Induced by Quarantine Hot Water Treatment

Abstract The application of a quarantine hot water treatment (HWT) induces chilling injury (CI) tolerance in mango fruit, but little is known about the mechanisms involved in this tolerance. The aim of this study was to identify metabolomic changes associated with HWT-induced CI tolerance in 'Keitt' mango fruit. Mature green fruit treated with hot water (HWT; 46.1 °C, 75-90 min) and non-treated (control) were stored for 20 d at 5 °C and ripened for 7 d at 21 °C. The incidence of chilling injury symptoms was registered as CI index. Methanol extracts of fruit peels were used for comparative metabolomics analyses by UPLC-DAD-MS and GC-MS. Total phenolics (TP) were analyzed by the Folin-Ciocalteu assay and the antioxidant activity (AA) was measured by ABTS, DPPH, and FRAP methods. HWT provided CI tolerance to mango fruit as evidenced by a low incidence of symptoms. Fifty-two and 14 metabolites were identified by UPLC-DAD-MS and GC-MS, respectively. These metabolites were classified as galloylquinic acids, gallic acid esters, gallotannins, gallic acid derivatives, benzophenone derivatives, xanthones, flavonoids, organic acids, sugars, fatty acids, and other metabolites (myo-inositol). The HWT before cold storage increased the abundance of galloylquinic acids, gallic acid esters, gallotannins, quercetin 3-O-rhamnoside, and myo-inositol; and it decreased the levels of mangiferin, ribose, malic acid, and palmitic acid. After cold storage and ripening, HWT fruit maintained higher levels of galloylquinic acids, gallic acid esters, gallotannins, quercetin 3-O-rhamnoside, mangiferin, myo-inositol, linolenic acid, and sugars than those in control fruit. HWT fruit also had higher values of TP and AA by the three methods. Control fruit had higher levels of citric acid, malic acid, palmitic acid, and ribose, as well as lower unsaturated/saturated fatty acid ratio. The HWT-induced CI tolerance in mango fruit appears to be associated with an increased content of antioxidants and osmoprotectant metabolites and a higher ratio of unsaturated/saturated fatty acids.

Polyphenol-Enriched Extracts from Trapa acornis Husks Inhibit Her2-Positive SK-BR-3 Breast Cancer Cell Proliferation and In Vivo Tumor Angiogenesis

The study aimed to investigate the antitumor effects of Trapa acornis husks (TAH) extract on SK-BR-3 cells of Her2-positive breast cancer. The bioactive compounds of TAH extracts were analyzed qualitatively and quantitatively by Ultra-Performance Liquid Chromatography/Mass Spectrometry (UPLC-MS)/high-performance liquid chromatographic system (HPLC). The effects of TAH extracts on cell proliferation, cell cycle, and apoptosis of SK-BR-3 cells were determined by CCK-8 and flow cytometry. Besides, the In Vivo antitumor effect of TAH extracts was detected. UPLC-MS/HPLC showed that the main bioactive compounds of TAH were gallic acid and galloylglucose derivatives. TAH extracts significantly inhibited the proliferation of SK-BR-3 cells in a dose- and time-dependent manner (P < 0.01). With the increase of TAH extracts concentration, cells in G2/M stage were increased and cell apoptosis was significantly increased. Immunohistochemical analysis showed that TAH extracts can significantly reduce the positive expression rate of Ki67 and Factor VIII index in tumor tissues. The mRNA expression levels of VEGF, MMP2, MMP9, and uPA were reduced after TAH extracts intervention (P < 0.01). TAH extracts also decreased the protein expression of p-Her2, p-ERK1/2, VEGF, MMP2, MMP9, and uPA (P < 0.01). In conclusion, polyphenol-enriched extracts from TAH might inhibit breast cancer cell proliferation and In Vivo tumor angiogenesis.

Synergistic Effects of Lauryl Gallate and Tamoxifen on Human Breast Cancer Cell.

Background:Tamoxifen (TAM) is widely used for adjuvant therapy in breast cancer patients. Tamoxifen therapy may lead to serious side effects. Anti-apoptotic substances in combination with chemotherapy drugs can result in additive or synergistic effects. Lauryl gallate (LG), a Gallic acid derivative, has been proven to inhibit tumor growth, without affecting normal cells. This study aimed to investigate the synergistic effect of TAM and LG in breast cancer cell line (MCF-7).Methods:In this experimental study, performed in ShahreKord University of Medical Science, Iran in 2017, the MCF-7 cells were treated by final concentrations of 10 μM TAM alone, and in combination with 200 μM of LG. We also used EX-527, as SIRT-1 inhibitor to examine the role of SIRT1 in cell apoptosis. BCL-2 and SIRT1 gene expression were measured by real-time PCR method, and cell apoptosis was investigated by flow cytometry.Results:Tamoxifen alone and in combination with LG decreased BCL-2 expression 2.64±0.75 and 6.38±1.9 fold, respectively, after 48 h (P<0.05). SIRT1 expression was increased 1.67±0.22 and 2.47±0.34 - fold by TAM alone and in combination with LG, respectively (P<0.05). TAM alone and in combination with LG increased the percentage of apoptotic cells 15.79±2.81 and 60.67±6.23 percent, respectively after 48 h (P<0.001).Conclusion:The combination of LG and TAM is more effective for induction of apoptosis of breast cancer cells, compared to individual use of each. Thus, our data pave the way for new therapeutic options for suppressing breast cancer growth.

Amide derivatives of Gallic acid: Design, synthesis and evaluation of inhibitory activities against in vitro α-synuclein aggregation

Gallic acid (GA), a natural phenolic acid, has received numerous attention because of its anti-oxidative, anti-inflammatory, and anti-cancer activity. More importantly, GA can act as an efficient inhibitor of α-Synuclein (α-Syn) aggregation at early stages. Nevertheless, some evidences suggest that GA is unlikely to cross the blood–brain barrier because of its high hydrophilicity. Hence, GA may not be considered as a promising candidate or entering brain and directly affecting the central nervous system. Accordingly, we have designed and synthesized a series of amide derivatives of GA, some of which possess appropriate lipophilicity and hydrophilicity with LogP (2.09–2.79). Meanwhile, these sheet-like conjugated compounds have good π-electron delocalization and high ability of hydrogen-bond formation. Some compounds have shown better in vitro anti-aggregation activities than GA towards α-Syn, with IC50 down to 0.98 μM. The valid modification strategy of GA is considered an efficient way to discover novel inhibitors of α-Syn aggregation.

Comparative studies of two vegetal extracts from Stokesia laevis and Geranium pratense: polyphenol profile, cytotoxic effect and antiproliferative activity

AbstractIn this study, two ethanolic extracts, fromStokesia aster(Slae26) andGeranium pratense(Gpre36) respectively, were evaluated in order to assess the cytotoxic activity and potential antiproliferative activity upon the nontumorigenic human epithelial cell line derived from the mammary gland (MCF-12A) and the human breast tumor cell line (BT-20). The selection of the plant species was done on the basis of their chemical composition, specifically combinations of luteolin derivatives with caffeic and gallic acid derivatives. Therefore, theS. laevisethanolic extract proved its capacity to inhibit the viability of both normal and tumor breast cell lines (i.e., up to 90% cell viability inhibition, IC50= 42 µg/mL). On the contrary, theG. pratenseethanolic extract proved weak stimulatory effects on the viability of the two human breast cell lines studied. The obtained results were discussed in the contexts of computational studies and drug-likeness bioactivity of seven common luteolin derivatives: luteolin, luteolin-7-O-glucoside/cynaroside, luteolin-5-O-glucoside/galuteolin, luteolin-6-C-glucoside/isoorientin, luteolin-8-C-glucoside/orientin, luteolin-3′,4′-di-O-glucoside and luteolin-7,3′-di-O-glucoside. Computational studies have revealed that the hydrophilic behavior of luteolin derivatives (log Pvalues) does not follow other tested parameters (e.g., polar surface area values), possibly explaining different efficacy concerning the biological propertiesin vitro. These predictions could be a starting point for studies on the biochemical mechanism by which luteolin derivatives induce biological effects.

Corilagin induces laryngeal cancer antiproliferation and inhibits growth factor and cytokine signaling pathways in vitro and in vivo

Laryngeal cancer is a prevalent malignancy of the head and neck with a high rate of mortality. Corilagin, a natural gallic acid derivative, was isolated from PhmLlanthi Fructus, a “drug homologous food”, and its in vitro and in vivo activity were investigated. Results of our study demonstrate that corilagin has significant anti-laryngeal cancer activity in vitro and in vivo. It was observed that corilagin inhibits proliferation and migration of cancerous laryngeal cells Hep-2 and TU212 in a concentration-dependent manner and inhibits growth of transplanted tumors in nude mice without apparent signs of toxicity. The anti-cancer effects of corilagin may be attributed to the inhibition of human laryngeal cancer proliferation by activation of mitochondrial apoptotic and endoplasmic reticulum stress signaling pathways and inhibition of Akt and STAT3 pathways.