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Among broad-spectrum anticancer agents, paclitaxel (PTX) has proven to be one of the most effective against solid tumors for which more specific treatments are lacking. However, drawbacks such as neurotoxicity and the development of resistance reduce its therapeutic efficacy. Therefore, there is a need for compounds able to improve its activity by synergizing with it or potentiating its effect, thus reducing the doses required. We investigated the interaction between PTX and tannins, other compounds with anticancer activity known to act as repressors of several proteins involved in oncological pathways. We found that both tannic acid (TA) and ethyl gallate (EG) strongly potentiate the toxicity of PTX in Hep3B cells, suggesting their utility in combination therapy. We also found that AT and EG promote tubulin polymerization and enhance the effect of PTX on tubulin, suggesting a direct interaction with tubulin. Biochemical experiments confirmed that TA, but not EG, binds tubulin and potentiates the apparent binding affinity of PTX for the tubulin binding site. Furthermore, the molecular docking of TA to tubulin suggests that TA can bind to two different sites on tubulin, one at the PTX site and the second at the interface of α and β-tubulin (cluster 2). The binding of TA to cluster 2 could explain the overstabilization in the tubulin + PTX combinatorial assay. Finally, we found that EG can inhibit PTX-induced expression of pAkt and pERK defensive protein kinases, which are involved in resistance to PXT, by limiting cell death (apoptosis) and favoring cell proliferation and cell cycle progression. Our results support that tannic acid and ethyl gallate are potential chemotherapeutic agents due to their potentiating effect on paclitaxel. [ABSTRACT FROM AUTHOR]

The tender shoots of Caesalpinia mimosoides Lam. are used ethnomedically by the traditional healers of Uttara Kannada district, Karnataka (India) for the treatment of wounds. The current study was aimed at exploring phenolenriched fraction (PEF) of crude ethanol extract of tender shoots to isolate and characterize the most active bio-constituent through bioassay-guided fractionation procedure. The successive fractionation and sub-fractionation of PEF, followed by in vitro scratch wound, antimicrobial, and antioxidant activities, yielded a highly active natural antioxidant compound ethyl gallate (EG). In vitro wound healing potentiality of EG was evidenced by a significantly higher percentage of cell migration in L929 fibroblast cells (97.98 ± 0.46% at 3.81 µg/ml concentration) compared to a positive control group (98.44 ± 0.36%) at the 48th hour of incubation. A significantly higher rate of wound contraction (98.72 ± 0.41%), an elevated tensile strength of the incised wound (1,154.60 ± 1.42 g/mm2), and increased quantity of connective tissue elements were observed in the granulation tissues of the 1% EG ointment treated animal group on the 15th post-wounding day. The accelerated wound healing activity of 1% EG was also exhibited by histopathological examinations through Hematoxylin and Eosin, Masson's trichome, and Toluidine blue-stained sections. Significant upregulation of enzymatic and non-enzymatic antioxidant contents (reduced glutathione, superoxide dismutase, and catalase) and down-regulation of oxidative stress marker (lipid peroxidation) clearly indicates the effective granular antioxidant activity of 1% EG in preventing oxidative damage to the skin tissues. Further, in vitro antimicrobial and antioxidant activities of EG supports the positive correlation with its enhanced wound-healing activity. Moreover, molecular docking and dynamics for 100 ns revealed the stable binding of EG with cyclooxygenase-2 (-6.2 kcal/mol) and matrix metalloproteinase-9 (-4.6 kcal/mol) and unstable binding with tumor necrosis factor-a (-7.2 kcal/mol), suggesting the potential applicability of EG in inflammation and wound treatment. [ABSTRACT FROM AUTHOR]

Bovine viral diarrhea virus (BVDV) is a highly contagious viral disease which causes economic losses to the cattle industry. Ethyl gallate (EG) is a phenolic acid derivative which has various potentials to modulate the host response to pathogens, such as via antioxidant activity, antibacterial activity, inhibition of the production of cell adhesion factors, and so on. This study aimed to evaluate if EG influences BVDV infection in Madin-Darby Bovine Kidney (MDBK) cells, and to understand the antiviral mechanism. Data indicated that EG effectively inhibited BVDV infection by co-treatment and post-treatment in MDBK cells with noncytotoxic doses. In addition, EG suppressed BVDV infection at an early stage of the viral life cycle by blocking entry and replication steps but not viral attachment and release. Moreover, EG strongly inhibited BVDV infection by promoting interferon-induced transmembrane protein 3 (IFITM3) expression, which localized to the cytoplasm. The protein level of cathepsin B was significantly reduced by BVDV infection, whereas with treatment with EG, it was significantly enhanced. The fluorescence intensities of acridine orange (AO) staining were significantly decreased in BVDV-infected cells but increased in EG-treated cells. Finally, Western blot and immunofluorescence analyses demonstrated that EG treatment significantly enhanced the protein levels of autophagy markers LC3 and p62. Chloroquine (CQ) significantly increased IFITM3 expression, and Rapamycin significantly decreased it. Thus, EG may regulate IFITM3 expression through autophagy. Our results showed that EG could have a solid antiviral activity on BVDV replication in MDBK cells via increased IFITM3 expression, lysosomal acidification, protease activity, and regulated autophagy. EG might have value for further development as an antiviral agent. [ABSTRACT FROM AUTHOR]

The tender shoots of Caesalpinia mimosoides Lam. are used ethnomedically by the traditional healers of Uttara Kannada district, Karnataka (India) for the treatment of wounds. The current study was aimed at exploring phenol-enriched fraction (PEF) of crude ethanol extract of tender shoots to isolate and characterize the most active bio-constituent through bioassay-guided fractionation procedure. The successive fractionation and sub-fractionation of PEF, followed by in vitro scratch wound, antimicrobial, and antioxidant activities, yielded a highly active natural antioxidant compound ethyl gallate (EG). In vitro wound healing potentiality of EG was evidenced by a significantly higher percentage of cell migration in L929 fibroblast cells (97.98 ± 0.46% at 3.81 μg/ml concentration) compared to a positive control group (98.44 ± 0.36%) at the 48th hour of incubation. A significantly higher rate of wound contraction (98.72 ± 0.41%), an elevated tensile strength of the incised wound (1,154.60 ± 1.42 g/mm2), and increased quantity of connective tissue elements were observed in the granulation tissues of the 1% EG ointment treated animal group on the 15th post-wounding day. The accelerated wound healing activity of 1% EG was also exhibited by histopathological examinations through Hematoxylin and Eosin, Masson’s trichome, and Toluidine blue-stained sections. Significant up-regulation of enzymatic and non-enzymatic antioxidant contents (reduced glutathione, superoxide dismutase, and catalase) and down-regulation of oxidative stress marker (lipid peroxidation) clearly indicates the effective granular antioxidant activity of 1% EG in preventing oxidative damage to the skin tissues. Further, in vitro antimicrobial and antioxidant activities of EG supports the positive correlation with its enhanced wound-healing activity. Moreover, molecular docking and dynamics for 100 ns revealed the stable binding of EG with cyclooxygenase-2 (−6.2 kcal/mol) and matrix metalloproteinase-9 (−4.6 kcal/mol) and unstable binding with tumor necrosis factor-α (−7.2 kcal/mol), suggesting the potential applicability of EG in inflammation and wound treatment.

The Castanopsis cuspidata var. sieboldii (CCS) plant grows predominantly in temperate regions of Asian countries, such as South Korea. Research on CCS has so far concentrated on the nutritional analysis, antioxidant activity, and anti-inflammation properties of its branches. However, the isolation of compounds and structural elucidation of effective single molecules remain unexplored, necessitating further exploration of CCS branches. Therefore, this study demonstrates the antioxidant and antimelanogenic activity of a single substance of ethyl gallate (EG) isolated from CCS branch extracts. Notably, the antimelanogenic (whitening) activity of EG extracted from CCS branches remains unexplored. Tyrosinase inhibition, kinetic enzyme assays, and molecular docking studies were conducted using mushroom tyrosinase in order to examine the antioxidant mechanism and antimelanin activity of EG in B16F10 melanoma cells. Nontoxic EG concentrations were found to be below 5 µg/mL. While EG significantly reduced the levels of whitening-associated proteins, p-CREB, and p-PKA, it dose-dependently inhibited the expression of TYR, TRP-1, TRP-2, and transcription factor (MITF). In addition, EG downregulated melanogenetic gene expression and activated autophagy signals. Therefore, EG extracted from CCS branches could serve as a novel functional cosmetic material with antimelanogenic and autophagy-enhancing activity. [ABSTRACT FROM AUTHOR]

Among broad-spectrum anticancer agents, paclitaxel (PTX) has proven to be one of the most effective against solid tumors for which more specific treatments are lacking. However, drawbacks such as neurotoxicity and the development of resistance reduce its therapeutic efficacy. Therefore, there is a need for compounds able to improve its activity by synergizing with it or potentiating its effect, thus reducing the doses required. We investigated the interaction between PTX and tannins, other compounds with anticancer activity known to act as repressors of several proteins involved in oncological pathways. We found that both tannic acid (TA) and ethyl gallate (EG) strongly potentiate the toxicity of PTX in Hep3B cells, suggesting their utility in combination therapy. We also found that AT and EG promote tubulin polymerization and enhance the effect of PTX on tubulin, suggesting a direct interaction with tubulin. Biochemical experiments confirmed that TA, but not EG, binds tubulin and potentiates the apparent binding affinity of PTX for the tubulin binding site. Furthermore, the molecular docking of TA to tubulin suggests that TA can bind to two different sites on tubulin, one at the PTX site and the second at the interface of α and β-tubulin (cluster 2). The binding of TA to cluster 2 could explain the overstabilization in the tubulin + PTX combinatorial assay. Finally, we found that EG can inhibit PTX-induced expression of pAkt and pERK defensive protein kinases, which are involved in resistance to PXT, by limiting cell death (apoptosis) and favoring cell proliferation and cell cycle progression. Our results support that tannic acid and ethyl gallate are potential chemotherapeutic agents due to their potentiating effect on paclitaxel.

Bovine viral diarrhea virus (BVDV) is a highly contagious viral disease which causes economic losses to the cattle industry. Ethyl gallate (EG) is a phenolic acid derivative which has various potentials to modulate the host response to pathogens, such as via antioxidant activity, antibacterial activity, inhibition of the production of cell adhesion factors, and so on. This study aimed to evaluate if EG influences BVDV infection in Madin-Darby Bovine Kidney (MDBK) cells, and to understand the antiviral mechanism. Data indicated that EG effectively inhibited BVDV infection by co-treatment and post-treatment in MDBK cells with noncytotoxic doses. In addition, EG suppressed BVDV infection at an early stage of the viral life cycle by blocking entry and replication steps but not viral attachment and release. Moreover, EG strongly inhibited BVDV infection by promoting interferon-induced transmembrane protein 3 (IFITM3) expression, which localized to the cytoplasm. The protein level of cathepsin B was significantly reduced by BVDV infection, whereas with treatment with EG, it was significantly enhanced. The fluorescence intensities of acridine orange (AO) staining were significantly decreased in BVDV-infected cells but increased in EG-treated cells. Finally, Western blot and immunofluorescence analyses demonstrated that EG treatment significantly enhanced the protein levels of autophagy markers LC3 and p62. Chloroquine (CQ) significantly increased IFITM3 expression, and Rapamycin significantly decreased it. Thus, EG may regulate IFITM3 expression through autophagy. Our results showed that EG could have a solid antiviral activity on BVDV replication in MDBK cells via increased IFITM3 expression, lysosomal acidification, protease activity, and regulated autophagy. EG might have value for further development as an antiviral agent.

The emergence of the high correlation between type 2 diabetes and obesity with complicated conditions has led to the coinage of the term "diabesity". AMP-activated protein kinase (AMPK) activators and peroxisome proliferator-activated receptor (PPARγ) antagonists have shown therapeutic activity for diabesity, respectively. Hence, the discovery of compounds that activate AMPK as well as antagonize PPARγ may lead to the discovery of novel therapeutic agents for diabesity. In this study, the knockdown of PTPN6 activated AMPK and suppressed adipogenesis in 3T3-L1 cells. By screening a library of 1033 natural products against PTPN6, we found ethyl gallate to be the most selective inhibitor of PTPN6 (Ki = 3.4 μM). Subsequent assay identified ethyl gallate as the best PPARγ antagonist (IC50 = 5.4 μM) among the hit compounds inhibiting PTPN6. Ethyl gallate upregulated glucose uptake and downregulated adipogenesis in 3T3-L1 cells as anticipated. These results strongly suggest that ethyl gallate, which targets both PTPN6 and PPARγ, is a potent therapeutic candidate to combat diabesity. [ABSTRACT FROM AUTHOR]

The Castanopsis cuspidata var. sieboldii (CCS) plant grows predominantly in temperate regions of Asian countries, such as South Korea. Research on CCS has so far concentrated on the nutritional analysis, antioxidant activity, and anti-inflammation properties of its branches. However, the isolation of compounds and structural elucidation of effective single molecules remain unexplored, necessitating further exploration of CCS branches. Therefore, this study demonstrates the antioxidant and antimelanogenic activity of a single substance of ethyl gallate (EG) isolated from CCS branch extracts. Notably, the antimelanogenic (whitening) activity of EG extracted from CCS branches remains unexplored. Tyrosinase inhibition, kinetic enzyme assays, and molecular docking studies were conducted using mushroom tyrosinase in order to examine the antioxidant mechanism and antimelanin activity of EG in B16F10 melanoma cells. Nontoxic EG concentrations were found to be below 5 µg/mL. While EG significantly reduced the levels of whitening-associated proteins, p-CREB, and p-PKA, it dose-dependently inhibited the expression of TYR, TRP-1, TRP-2, and transcription factor (MITF). In addition, EG downregulated melanogenetic gene expression and activated autophagy signals. Therefore, EG extracted from CCS branches could serve as a novel functional cosmetic material with antimelanogenic and autophagy-enhancing activity.

Qi Zhang,1 Jing Nie,2 Su-Juan Chen,2 Qiang Li2 1Department of Natural Medicine, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350122, China; 2School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China Background: The aim of this study was to investigate the bioactive constituents of Qingwen Baidu Decoction (QBD) in a rat model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Our previous studies showed that ethyl gallate (EG) and pentagalloylglucose (PGG) were the active components of QBD for the treatment of ALI. Materials and methods: We isolated two compounds and identified the structures of them by nuclear magnetic resonance and mass spectrometer. Lung injury was induced by intratracheal instillation with LPS (5 mg/kg). Rats were randomly divided into six groups: Control group; LPS group; 5 mL/kg DEX + LPS group; 6.6 g/kg QBD extract + LPS group; 17.16 mg/kg PGG + LPS group; 7.26 mg/kg EG + LPS group. The effects of compounds on LPS-induced the number of total cells, neutrophils influx, protein leakage, W/D weight ratio and pulmonary histological changes were examined. Results: The results demonstrated that pretreatment with EG and PGG could notably inhibit lung edema and attenuate the pulmonary histological changes (P

The emergence of the high correlation between type 2 diabetes and obesity with complicated conditions has led to the coinage of the term “diabesity”. AMP-activated protein kinase (AMPK) activators and peroxisome proliferator-activated receptor (PPARγ) antagonists have shown therapeutic activity for diabesity, respectively. Hence, the discovery of compounds that activate AMPK as well as antagonize PPARγ may lead to the discovery of novel therapeutic agents for diabesity. In this study, the knockdown of PTPN6 activated AMPK and suppressed adipogenesis in 3T3-L1 cells. By screening a library of 1033 natural products against PTPN6, we found ethyl gallate to be the most selective inhibitor of PTPN6 (Ki = 3.4 μM). Subsequent assay identified ethyl gallate as the best PPARγ antagonist (IC50 = 5.4 μM) among the hit compounds inhibiting PTPN6. Ethyl gallate upregulated glucose uptake and downregulated adipogenesis in 3T3-L1 cells as anticipated. These results strongly suggest that ethyl gallate, which targets both PTPN6 and PPARγ, is a potent therapeutic candidate to combat diabesity.

The usefulness of the structure of galloyl hydrazide (3,4,5-trihydroxybenzohydrazide, coded as 2nz in this article) as a privileged structural system in pharmaceutical organic and medicinal chemistry has prompted the advances of the further therapeutic potentials of this known antioxidant/antitumor compound and, in addition to that, it acts generally as a very important organic reaction intermediate for molecule planning (including synthesis of many important biologically active molecules), as it undergoes various types of chemical reactions. The data of the two synthetic methods (including the new green one), presented in this research article, provides sharp adequate chemical data about the challenging synthesis, separation (purification), and characterization of this compound. A new and very fast one-pot solventless greener microwave-assisted method of synthesis, in addition to the much slower old conventional one, is used in this present research; and followed by full precise purification and characterization (including chromatographic separation; physicochemical identification; IR, 1H-NMR, 13C-NMR, and mass spectroscopic analyses along with elemental analyses for structure elucidation) of 2nz. • Galloyl hydrazide is a very important and unique organic chemical intermediate with, mainly, antioxidant and anticancer biological activities. • Galloyl hydrazide synthesis in the previous literature is very challenging, confusing, not standardized, and without any consensus. • The main objective of this new research is to make two standard and fixed methods of synthesis (conventional and greener) of galloyl hydrazide through designing and constructing a new one-pot solventless greener microwave-assisted synthetic method, in addition to redesigning and qualifying the old traditional conventional heating one; both methods are followed by very accurate identification and characterization data (which can be referenced for the efficient reproducibility in the organic and pharmaceutical chemistry community) of galloyl hydrazide.

OBJECTIVES: The objective of this study is to analyze the antiproliferative activity of Acacia nilotica (L.) leaf ethanolic extract against cancer KB cells and to determine the mode of cancer cytotoxicity. MATERIALS AND METHODS: In this study, high-performance liquid chromatography and liquid chromatography-mass spectrometry analysis were done to confirm the presence of ethyl gallate as a major bioactive phenolic in the leaf ethanolic extract of A. nilotica, further dose-dependent (0–120 μg/mL) antiproliferative effect was investigated in human carcinoma cell line KB. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, reactive oxygen species, mitochondrial membrane potential loss, DNA damage, and apoptosis were evaluated. RESULTS: A. nilotica leaf ethanolic extract (ANLEE) showed effective concentration (EC50) of 40 μg/mL. Interference of growth was significantly (P < 0.05) high in KB cells treated with ANLEE when compared to untreated control, but less when compared to the reference drug paclitaxel. In addition, the in vivo acute toxicity study demonstrated the safe limit of administration of 2000 mg/kg body weight ANLEE by the histological analysis in rats. The results from the present study indicate that mitochondria and DNA of KB cells are severely affected leading to apoptosis. CONCLUSIONS: ANLEE is a prospective source for cancer therapy and therefore should be highlighted to explore on its wide range of safety in rats and efficacy against human carcinoma cell line KB. [ABSTRACT FROM AUTHOR]

Metronidazole (MTZ) is an antibacterial drug widely used for the treatment of protozoan and anaerobic infections in humans and animals. However, its low bioavailability necessitates the frequent administration of a high dose to attain an effective plasma concentration profile for therapy. To reduce the dose of MTZ, we have prepared a new cocrystal between MTZ and ethyl gallate (EG). The solid-state properties of MTZ-EG were characterized using complimentary techniques, including thermal, spectroscopic, microscopic, and X-ray crystallographic methods. The MTZ-EG cocrystal exhibits a higher solubility and faster dissolution than MTZ. The bioavailability of MTZ in rats was increased by 36% when MTZ-EG was used.

Helicanthus elastica (Desr.) Danser (Loranthaceae) is a less-known medicinally important mistletoe species occurring in India. It is used to check abortion, and also in vesical calculi and kidney affections. There are no detailed studies reporting the antimicrobial potential of this plant. Based on the traditional use and the rich phenolic composition of the whole plant, the antimicrobial property of the alcohol extract was analyzed and the results are outlined in the present paper. For the analysis, zone of inhibition, and minimum inhibitory concentration were used, and the total activity was assayed by standard methodologies. The antimicrobial activity was studied against bacteria like Aeromonas hydrophila, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes, Vibrio fischeri, and a fungus Candida albicans. Of the eight tested bacteria, the alcoholic extract of H. elastica was found to be active against K. pneumoniae, A. hydrophila, E. coli, and V. fischeri at concentration ranging from 250 to 500 μg/ml. C. albicans showed inhibition only at a concentration of 2000 μg/ml.

Plant species have traditionally been revered for their unparalleled pharmacognostic applications. We outline a non-iterative multi-parallel metabolomic-cum-bioassay-guided methodology toward the functional characterization of ethanol extracts from the Betulaceae family plants (n = 10). We performed mass spectrometry (MS)-based multivariate analyses and bioassay-guided (ABTS antioxidant activity and cytoprotective effects against H2O2-induced cell damage) analyses of SPE fractions. A clearly distinct metabolomic pattern coupled with significantly higher bioactivities was observed for 40% methanol SPE eluate. Further, the 40% SPE eluate was subjected to preparative high-performance liquid chromatography (prep-HPLC) analysis, yielding 72 sub-fractions (1 min−1), with the highest antioxidant activities observed for the 15 min and 31 min sub-fractions. We simultaneously performed hyphenated-MS-based metabolite characterization of bioactive components for both the 40% methanol SPE fraction and its prep-HPLC sub-fraction (15 min and 31 min). Altogether, 19 candidate metabolites were mainly observed to contribute toward the observed bioactivities. In particular, ethyl gallate was mainly observed to affect the antioxidant activities of SPE and prep-HPLC fractions of Alnus firma extracts. We propose an integrated metabolomic-cum-bioassay-guided approach for the expeditious selection and characterization of discriminant metabolites with desired phenotypes or bioactivities.

This study aimed to test the effectiveness of ethyl gallate (EG) against S. mutans biofilm formation on solid surfaces (polystyrene, glass) and acidogenicity, and to examine the effect on expression of related genes. The biofilm that is formed by S. mutans bacteria was evaluated using colorimetric assay and optical profilometry, while the pH of the biofilm growth medium was measured with microelectrode. The expression of genes encoding glucan binding protein B (gbpB), glucosyltranferases B, -C, -D (gtfB, -C, -D) and F-ATPase (atpD, atpF) was assessed using a quantitative reverse transcription-polymerase chain reaction (RT-qPCR). It was revealed that all of the EG concentrations significantly suppressed S. mutans biofilm build-up on polystyrene and glass surfaces, and inhibited acidogenicity, in a dose-dependent manner, compared to the activity of untreated bacteria (p < 0.05). The highest concentration of EG (3.53 mM) reduced biofilm formation on polystyrene and glass surfaces by 68% and more than 91%, respectively, and prevented a decrease in pH levels by 95%. The RT-qPCR data demonstrate that the biofilm-producing bacteria treated with EG underwent significant gene expression changes involving the gtfC (a 98.6 increase in fold change), gtfB gene (a 47.5 increase in fold change) and the gbpB gene (a 13.8 increase in fold change). However, for the other genes tested (gtfD, atpD and atpF), the EG treatments did not produce significant expression change compared to the control. EG produced significant gene expression change in three genes—gtfC, gtfB, and gbpB; it has the capacity to inhibit S. mutans biofilm formation on solid surfaces (polystyrene, glass), as well as acidogenicity. Therefore, EG might be used as an antibiofilm and/or anticaries agent for oral formulations in order to reduce the prevalence of dental caries.

Caesalpinia coriaria (C. coriaria), also named cascalote, has been known traditionally in México for having cicatrizing and inflammatory properties. Phytochemical reports on Caesalpinia species have identified a high content of phenolic compounds and shown antineoplastic effects against cancer cells. The aim of this study was to isolate and identify the active compounds of a water:acetone:ethanol (WAE) extract of C. coriaria pods and characterize their cytotoxic effect and cell death induction in different cancer cell lines. The compounds isolated and identified by chromatography and spectroscopic analysis were stigmasterol, ethyl gallate and gallic acid. Cytotoxic assays on cancer cells showed different ranges of activities. A differential effect on cell cycle progression was observed by flow cytometry. In particular, ethyl gallate and tannic acid induced G2/M phase cell cycle arrest and showed interesting effect on microtubule stabilization in Hep3B cells observed by immunofluorescence. The induction of apoptosis was characterized by morphological characteristic changes, and was supported by increases in the ratio of Bax/Bcl-2 expression and activation of caspase 3/7. This work constitutes the first phytochemical and cytotoxic study of C. coriaria and showed the action of its phenolic constituents on cell cycle, cell death and microtubules organization. [ABSTRACT FROM AUTHOR]

Many phytochemicals have been recognized to have potential therapeutic efficacy in cancer treatment. In this study, we investigated ethyl gallate (EG) for possible proapoptotic effects in the human promyelocytic leukemia cell line, HL-60. We examined cell viability, morphological changes, DNA content and fragmentation, and expression of apoptosis-related proteins for up to 48 h after EG treatment. The results showed that EG induced morphological changes and DNA fragmentation and reduced HL-60 cell viability in a dose-dependent and time-dependent manner. Western blotting analysis indicated that EG-mediated HL-60 apoptosis mainly occurred through the mitochondrial pathway, as shown by the release of cytochrome c, apoptosis-inducing factor (AIF), and endonuclease G (Endo G), as well as the upregulation of Bcl-2-associated X protein (Bax). EG also activated the death receptor-dependent pathway of apoptosis by enhancing the expression of caspases-8, -9, and -3 and the Bcl-2 interacting domain (Bid). Collectively, our results showed that EG induces apoptosis in HL-60 via mitochondrial-mediated pathways.

Ethyl gallate is a phenolic compound richly contained in Longan. In traditional Chinese medicine, Longan is widely known as a fruit with “hot” properties, with a tendency to promote inflammatory and certain other responses. The mechanism for its proinflammatory as well as health beneficial effects is poorly understood. Based on our earlier observation that certain natural phenolic compounds can serve as reducing cosubstrates for cyclooxygenases (COXs), we sought to test a hypothesis that ethyl gallate may activate the catalytic activity of the COX enzymes. Results from studies using cultured cells and animals show that ethyl gallate can activate the production of prostaglandin E2, a representative prostaglandin tested in this study. Computational analysis indicates that ethyl gallate can activate the peroxidase active sites of COX-1 and COX-2 by serving as a reducing cosubstrate. The effect of ethyl gallate is abrogated by galangin, which is known to bind to the same peroxidase active sites of COX-1 and COX-2 as a competitive inhibitor. The findings of this study offer support for a novel hypothesis that the proinflammatory as well as health beneficial effects of Longan may be partly attributable to the activation of COX-1 and COX-2 by ethyl gallate.

Background: To extract, purify, and identify the effective constituents of aqueous extract of Fructus Chebulae Immaturus, and analyze the bactericidal effects of total tannins. Methods: Preparative thin layer chromatography and semi-preparative high performance liquid chromatography were used to isolate and purify the total tannin fraction. ¹H- and 13C- NMR spectroscopy were used to elucidate compound structures. The antibacterial activities of total tannins and ethyl gallate on Klebsiella pneumoniae (KP) and Staphylococcus aureus (SA) were determined through minimum inhibitory concentration and minimum bactericidal concentration assays. Their antibacterial mechanisms of action were explored by transmission electron microscopy and scanning electron microscopy. Results: Five compounds were isolated: ellagic acid, ethyl gallate, arjugenin, β-sitosterol, and tri-n-butyl chebulate. Tri-n-butyl chebulate is a newly-reported compound. Total tannins and ethyl gallate both had favorable bactericidal effects against KP and SA. Conclusion: In vivo and in vitro pharmacodynamic experiment demonstrated that the effective components of Fructus Chebulae Immaturus possessed significant antibacterial effects, and were nontoxic and safe. Trial registration: No results of a health care intervention on human participants [ABSTRACT FROM AUTHOR]

Background Recently, enormous research has been focused on natural bioactive compounds possessing potential antioxidant and anticancer properties using cell lines and animal models. Acacia nilotica (L.) is widely distributed in Asia, Africa, Australia and Kenya. The plant is traditionally used to treat mouth, ear and bone cancer. However, reports on Acacia nilotica (L.) Wild. Ex. Delile subsp. indica (Benth.) Brenan regarding its toxicity profile is limited. Hence in this study, we investigated the antioxidant capacity and acute toxicity of ethyl gallate, a phenolic antioxidant present in the A. nilotica (L.) leaf extract. Methods The antioxidant activity of ethyl gallate against Fenton’s system (Fe3+/H2O2/ascorbic acid) generated oxidative damage to pBR322 DNA and BSA was investigated. We also studied the interaction of ethyl gallate to CT-DNA by wave scan and FTIR analysis. The amount of ethyl gallate present in the A. nilotica (L.) leaf extract was calculated using HPLC and represented in gram equivalence of ethyl gallate. The acute toxicity profile of ethyl gallate in the A. nilotica (L.) leaf extract was analyzed in albino Wistar rats. Measurement of liver and kidney function markers, total proteins and glucose were determined in the serum. Statistical analysis was done using statistical package for social sciences (SPSS) tool version 16.0. Results Ethyl gallate was found to be effective at 100 μg/mL concentration by inhibiting the free radical mediated damage to BSA and pBR322 DNA. We also found that the interaction of ethyl gallate and A. nilotica (L.) leaf extract to CT-DNA occurs through intercalation. One gram of A. nilotica (L.) leaf extract was found to be equivalent to 20 mg of ethyl gallate through HPLC analysis. Based on the acute toxicity results, A. nilotica (L.) leaf extract and ethyl gallate as well was found to be non-toxic and safe. Conclusions Results revealed no mortality or abnormal biochemical changes in vivo and the protective effect of A. nilotica (L.) leaf extract and ethyl gallate on DNA and protein against oxidative stress in vitro. Hence, A. nilotica (L.) leaf extract or ethyl gallate could be used as potential antioxidants with safe therapeutic application in cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract: The change in size and structure of monodisperse poly(N-isopropylacrylamide) (PNIPAM) microcapsules in response to varying temperature and ethyl gallate (EG) concentration has been investigated systematically. Monodisperse PNIPAM microspheres and core-shell microcapsules were fabricated via a microfluidic approach. The volume phase transition temperature (VPTT) of PNIPAM microspheres in aqueous solutions with varying EG concentrations were investigated systematically, and the experimental results showed that the VPTT of PNIPAM microspheres in EG aqueous solution decreased with increasing the EG concentration, due to the hydrogen bonding between PNIPAM networks and EG molecules. The change in size and structure of core-shell PNIPAM microcapsules in response to varying temperature and EG concentration was investigated visually by using a confocal laser scanning microscope (CLSM). The core-shell PNIPAM microcapsules changed their volume from swollen to shrunken state upon heating or increasing the EG concentration, and released the colored oil cores suddenly when the environmental temperature was increased to just above the VPTT or the EG concentration was increased to above a critical concentration. From the experimental data, a state diagram of the intact-to-broken transformation of core-shell PNIPAM microcapsules in aqueous solution as a function of temperature and EG concentration has been constructed for the first time. [Copyright &y& Elsevier]

Many phytochemicals have been recognized to have potential therapeutic efficacy in cancer treatment. In this study, we investigated ethyl gallate (EG) for possible proapoptotic effects in the human promyelocytic leukemia cell line, HL-60. We examined cell viability, morphological changes, DNA content and fragmentation, and expression of apoptosis-related proteins for up to 48 h after EG treatment. The results showed that EG induced morphological changes and DNA fragmentation and reduced HL-60 cell viability in a dose-dependent and time-dependent manner. Western blotting analysis indicated that EG-mediated HL-60 apoptosis mainly occurred through the mitochondrial pathway, as shown by the release of cytochrome c, apoptosis-inducing factor (AIF), and endonuclease G (Endo G), as well as the upregulation of Bcl-2-associated X protein (Bax). EG also activated the death receptor-dependent pathway of apoptosis by enhancing the expression of caspases-8, -9, and -3 and the Bcl-2 interacting domain (Bid). Collectively, our results showed that EG induces apoptosis in HL-60 via mitochondrial-mediated pathways. [ABSTRACT FROM AUTHOR]

Arjunarishta (Parthadyarishta) is an important Ayurvedic formulation used for cardiovascular disorders and is prepared by fermenting the decoction of specified plant materials using flowers of Woodfordia fruticosa. In present communication, an HPLC-PDA method was developed for the standardization of Arjunarishta by quantitative estimation of major antioxidant compounds, ellagic acid, gallic acid, ethyl gallate, quercetin and kaempferol as markers. The developed method was validated with respect to linearity, precision, accuracy, and robustness. The HPLC analysis showed an increase in amount of ellagic acid and gallic acid during preparation, i.e. decoction vs formulation. A similar increase in free radical scavenging activity of formulation vs decoction was also observed. Arjunolic acid and arjunic acid were not detected in the formulation. [ABSTRACT FROM AUTHOR]