Combined administration of gallic acid and glibenclamide mitigate systemic complication and histological changes in the cornea of diabetic rats induced with streptozotocin

Purpose: To determine the effect of gallic acid or its combination with glibenclamide on some biochemical markers and histology of the cornea of streptozotocin (STZ) induced diabetic rats. Methods: Following induction of diabetes, 24 male albino rats were divided into four groups of six rats each. Groups 1 and 2 (control and diabetic) received rat pellets and distilled water; group 3 (gallic acid) received rat pellets and gallic acid (10 mg/kg, orally) dissolved in the distilled water; and group 4 (gallic acid + glibenclamide) received rat pellets, gallic acid (10 mg/kg, orally), and glibenclamide (5 mg/kg, orally) dissolved in the distilled water. The treatments were administered for three months after which the rats were sacrificed after an overnight fast. Blood and sera were collected for the determination of biochemical parameters, while their eyes were excised for histology. Results: STZ administration to the rats induced insulin resistance, hyperglycemia, microprotenuria, loss of weight, oxidative stress, inflammation, and alteration of their cornea histology, which was abolished following supplementation with gallic acid or its combination with glibenclamide. Conclusions: The study showed the potentials of gallic acid and glibenclamide in mitigating systemic complication and histological changes in the cornea of diabetic rats induced with STZ.

Effect and mechanism of leonurine on pressure overload-induced cardiac hypertrophy in rats / 中国中药杂志

To investigate the effects of leonurine(Leo) on abdominal aortic constriction(AAC)-induced cardiac hypertrophy in rats and its mechanism. A rat model of pressure overload-induced cardiac hypertrophy was established by AAC method. After 27-d intervention with high-dose(30 mg·kg~(-1)) and low-dose(15 mg·kg~(-1)) Leo or positive control drug losartan(5 mg·kg~(-1)), the cardiac function was evaluated by hemodynamic method, followed by the recording of left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVESP), as well as the maximum rate of increase and decrease in left ventricular pressure(±dp/dt_(max)). The degree of left ventricular hypertrophy was assessed based on heart weight index(HWI) and left ventricular mass index(LVWI). Myocardial tissue changes and the myocardial cell diameter(MD) were measured after hematoxylin-eosin(HE) staining. The contents of angiotensin Ⅱ(AngⅡ) and angiotensin Ⅱ type 1 receptor(AT1 R) in myocardial tissue were detected by ELISA. The level of Ca~(2+) in myocardial tissue was determined by colorimetry. The protein expression levels of phospholipase C(PLC), inositol triphosphate(IP3), AngⅡ, and AT1 R were assayed by Western blot. Real-time quantitative PCR(qRT-PCR) was employed to determine the mRNA expression levels of β-myosin heavy chain(β-MHC), atrial natriuretic factor(ANF), AngⅡ, and AT1 R. Compared with the model group, Leo decreased the LVSP, LVEDP, HWI, LVWI and MD values, but increased ±dp/dt_(max) of the left ventricle. Meanwhile, it improved the pathological morphology of myocardial tissue, reduced cardiac hypertrophy, edema, and inflammatory cell infiltration, decreased the protein expression levels of PLC, IP3, AngⅡ, AT1 R, as well as the mRNA expression levels of β-MHC, ANF, AngⅡ, AT1 R, c-fos, and c-Myc in myocardial tissue. Leo inhibited AAC-induced cardiac hypertrophy possibly by influencing the RAS system.

Gallic Acid: A Potential Anti-Cancer Agent / 中国结合医学杂志

Cancer is one of the most devastating diseases worldwide and definitive therapeutics for treating cancer are not yet available despite extensive research efforts. The key challenges include limiting factors connected with traditional chemotherapeutics, primarily drug resistance, low response rates, and adverse side-effects. Therefore, there is a high demand for novel anti-cancer drugs that are both potent and safe for cancer prevention and treatment. Gallic acid (GA), a natural botanic phenolic compound, can mediate various therapeutic properties that are involved in anti-inflammation, anti-obesity, and anti-cancer activities. More recently, GA has been shown to exert anti-cancer activities via several biological pathways that include migration, metastasis, apoptosis, cell cycle arrest, angiogenesis, and oncogene expression. This review discusses two aspects, one is the anti-cancer potential of GA against different types of cancer and the underlying molecular mechanisms, the other is the bibliometric analysis of GA in cancer and tumor research. The results indicated that lung cancer, prostate cancer, stomach cancer, and colon adenocarcinoma may become a hot topic in further research. Overall, this review provides evidence that GA represents a promising novel, potent, and safe anti-cancer drug candidate for treating cancer.

Inhibition of α-glucosidase, pancreatic lipase, and antioxidant property of Myrcia hatschbachii D. Legrand containing gallic and ellagic acids / Inhibición de la α-glucosidasa, la lipasa pancreática y la propiedad antioxidante de Myrcia hatschbachii D. Legrand que contiene ácidos gálico y elágico

Several species of the Myrcia genus have been used in folk medicine to treat diabetes. Therefore, the aim of this work was to investigate the inhibitory activity of α-glucosidase and pancreatic lipase in the crude extract (EBF) and in the ethyl acetate fraction (FFA) of Myrcia hatschbachii, as well as to identify isolated phenolic compounds and to evaluate the antioxidant property and preliminary in vitro toxicity against Artemia salina. EBF (IC50: 3.21 µg/mL) and FFA (IC50: 1.14 µg/mL) showed inhibitory activity superior to acarbose (IC50: 193.65 µg/mL). In addition, they showed inhibitory effects of pancreatic lipase (IC50: 556.58 µg/mL for EBF and 532.68 µg/mL for FFA), antioxidant potential, absence of preliminary toxicity and presence of gallic andellagic acids in FFA. The relevant results in the inhibition of α-glucosidase and pancreatic lipase motivate new studies for the development of herbal medicines that assist in the treatment of diabetic patients.

Varias especies del género Myrcia se han utilizado en la medicina popular para tratar la diabetes. Por lo tanto, el objetivo de este trabajo fue investigar la actividad inhibitoria de la α-glucosidasa y la lipasa pancreática en el extracto crudo (EBF) y en la fracción de acetato de etilo (FFA) de Myrcia hatschbachii, así como identificar compuestos fenólicos aislados y evaluar la propiedad antioxidante y toxicidad in vitro preliminar contra Artemia salina. EBF (IC50: 3.21 µg/mL) y FFA (IC50: 1.14 µg/mL) mostraron una actividad inhibitoria superior a la acarbosa (IC50: 193.65 µg/mL). Además, mostraron efectos inhibitorios de la lipasa pancreática (IC50: 556.58 µg/mL para EBF y 532.68 µg/mL para FFA), potencial antioxidante, ausencia de toxicidad preliminar y presencia de ácidos gálico y elágico en FFA. Los resultados relevantes en la inhibición de la α-glucosidasa y la lipasa pancreática motivan nuevos estudios para el desarrollo de medicamentos a base de hierbas que ayudan en el tratamiento de pacientes diabéticos.

Castor Bean Cake Protein-based Biodegradable Films: Gallic Acid Effect

Abstract: The objective of this work was to evaluate the effect of gallic acid (GA) concentration on some physical properties and biodegradability of films produced with proteins extracted from the castor bean cake. The films, prepared by the casting technique, showed homogeneous and brownish appearance. As the GA concentration increased (from 0 to 10 g/100 g protein), the films gradually became darker and more opaque; while the gloss had few significant differences. Solubility, tensile strength and elasticity modulus values of films varied due to changing concentrations of gallic acid. Elongation at break and water vapor permeability values did not have significant changes. A 60% mineralization value of the film containing GA was obtained at 21 days, evidencing its biodegradability. These dark and opaque films could be used in agriculture, specifically in seedling bags as the dark color decrease the incidence of light, preventing root weakening, and the seedlings can be transplanted directly without removal of the film.

Renoprotective Effects of Gallic Acid Against Gentamicin Nephrotoxicity Through Amelioration of Oxidative Stress in Rats

Abstract Gallic acid (GA), as a strong antioxidant, was selected in this study to investigate its possible nephroprotective effects against gentamicin (GM)-induced nephrotoxicity. Twenty-four rats were separated into three groups (n=8): group 1 (control group) received saline (0.5 mL/day), group 2 (GM group) received GM (100 mg/kg/day), and group 3 (treated group) received GM (100 mg/kg/day) and GA (100mg/kg/day). All treatments were performed intraperitoneally for 12 days. After 12 days, the rats were euthanized, and kidneys were removed immediately. For serum preparation, blood samples were collected before killing. Kidney paraffin sections were prepared from one of the kidneys and stained by the periodic acid-Schiff process. GA significantly decreased GM-induced renal histopathological injuries, including tubular necrosis, tubular cast, and leucocyte infiltration compared with the GM group. Additionally, GA significantly improved proteinuria, serum levels of urea and creatinine, and serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with nephrotoxic animals. Furthermore, GA caused a significant improvement in the levels of cholesterol (Chol), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and cardiac risk ratios 1 and 2 in comparison with nephrotoxic animals. GA administration was observed to significantly improve the levels of lipid peroxidation, nitric oxide (NO), and glutathione (GSH) compared with the GM group. Finally, the activities and gene expression levels of catalase (CAT) and glutathione peroxidase (GPX) significantly increased following GA administration compared with the GM group. Our results indicated that GA has potential protective effects against GM nephrotoxicity by reducing oxidative stress in rats.

Protective effect of gallic acid against cisplatin-induced ototoxicity in rats / Efeito protetor do ácido gálico contra a ototoxicidade induzida por cisplatina em ratos

Abstract Introduction: Cisplatin is an antineoplastic agent widely used in the treatment of a variety of cancers. Ototoxicity is one of the main side-effects restricting the use of cisplatin. Objective: The purpose of this study was to investigate the protective efficacy of gallic acid, in biochemical, functional and histopathological terms, against ototoxicity induced by cisplatin. Methods: Twenty-eight female Sprague Dawley rats were included. Rats were randomly assigned into four groups of seven animals each. Cisplatin group received a single intraperitoneal dose of 15 mg/kg cisplatin. Gallic acid group received intraperitoneal gallic acid at 100 mg/kg for five consecutive days. Cisplatin + gallic acid group received intraperitoneal gallic acid at 100 mg/kg for five consecutive days and a single intraperitoneal dose of 15 mg/kg cisplatin at 3rd day. A control group received 1 mL intraperitoneal saline solution for five consecutive days. Prior to drug administration, all rats were exposed to the distortion product otoacoustic emissions test. The test was repeated on the 6th day of the study. All rats were then sacrificed; the cochleas were removed and set aside for biochemical and histopathological analyses. Results: In cisplatin group, Day 6 signal noise ratio values were significantly lower than those of the other groups. Also, malondialdehyde levels in cochlear tissues were significantly higher, superoxide dismutase and glutathione peroxidase activities were significantly lower compared to the control group. Histopathologic evaluation revealed erosion in the stria vascularis, degeneration and edema in the connective tissue layer in endothelial cells, impairment of outer hair cells and a decrease in the number of these calls. In the cisplatin + gallic acid group, this biochemical, histopathological and functional changes were reversed. Conclusion: In the light of our findings, we think that gallic acid may have played a protective role against cisplatin-induced ototoxicity in rats, as indicated by the distortion product otoacoustic emissions test results, biochemical findings and immunohistochemical analyses.

Resumo Introdução: A cisplatina é um agente antineoplásico amplamente usado no tratamento de vários tipos de câncer. A ototoxicidade é um dos principais efeitos colaterais que restringem o uso da cisplatina. Objetivo: O objetivo deste estudo foi investigar a eficácia protetora do ácido gálico, em termos bioquímicos, funcionais e histopatológicos, contra a ototoxicidade induzida por cisplatina. Método: Vinte e oito ratas Sprague-Dawley foram incluídas. As ratas foram distribuídas aleatoriamente em quatro grupos de sete animais cada. O grupo cisplatina recebeu uma única dose intraperitoneal de 15 mg/kg de cisplatina. O grupo ácido gálico recebeu ácido gálico via intraperitoneal a uma dose de 100 mg/kg durante cinco dias consecutivos. O grupo cisplatina + ácido gálico recebeu ácido gálico via intraperitoneal a uma dose de 100 mg/kg durante cinco dias consecutivos e uma única dose intraperitoneal de 15 mg/kg de cisplatina no terceiro dia. O grupo controle recebeu 1 mL de solução salina via intraperitoneal por cinco dias consecutivos. Antes da administração do fármaco, todos os ratos foram expostos ao teste de emissões otoacústicas - produto de distorção. O teste foi repetido no sexto dia do estudo. Todos os ratos foram então sacrificados; as cócleas foram removidas e reservadas para análises bioquímicas e histopatológicas. Resultados: No grupo cisplatina, os valores da relação sinal-ruído do dia 6 foram significativamente mais baixos aos dos outros grupos. Além disso, os níveis de malondialdeído nos tecidos cocleares foram significativamente mais altos, e as atividades de superóxido dismutase e glutatione peroxidase foram significativamente mais baixas em comparação com o grupo controle. A avaliação histopatológica revelou erosão na estria vascular, degeneração e edema na camada de tecido conjuntivo em células endoteliais, comprometimento das células ciliadas externas e diminuição do número dessas células. No grupo cisplatina + ácido gálico, estas alterações bioquímicas, histopatológicas e funcionais foram revertidas. Conclusão: Tendo em vista os nossos achados, consideramos que o ácido gálico pode ter desempenhado um papel protetor contra a ototoxicidade induzida por cisplatina em ratas, conforme indicado pelos resultados do teste emissões otoacústicas - produto de distorção, achados bioquímicos e análises imuno-histoquímicas.

Effects of gallic acid and physical exercise on passive avoidance memory in male rat

Learning and memory play main roles in daily life of human, and memory represents the basis of all trainings and learning. The aim of the current study is to investigate the effects of gallic acid and physical exercise on the levels of passive avoidance memory in rat. In this experimental study, 46 rats weighing 200-300 g were randomLy divided to six groups of eight each: including control group, groups treated with 10 and 20 mg/kg gallic acid, group undergoing physical exercise alone, and groups both undergoing physical exercise and treated with 10 and 20 mg/kg gallic acid. The interventions continued for 10 days. After the intervention, passive avoidance memory was measured by shuttle box, blood samples were taken, and serum and brain antioxidant capacity and malondialdehyde (MDA) levels were measured. Secondary latency in shuttle box significantly increased in groups undergoing treadmill exercise and undergoing treadmill exercise + treating 10 and 20 mg/kg gallic acid. In groups treated with 10 and 20 mg/kg gallic acid alone, secondary latency increased significantly. Results confirmed the effects of gallic acid and physical exercise, either alone or combined, in improving memory.

Effect of gallic acid addition on some mechanical properties of self-adhesive resin cements

Abstract Self-adhesive resin cements (RCs) activate matrix metalloproteinase (MMP) and cathepsin-related collagen degradation, and gallic acid (GA) inhibits the activity of both MMPs and cysteine cathepsins. The purpose of this study was to evaluate the setting time, biaxial flexural strength, and Vickers hardness of self-adhesive RCs after the addition of two different concentrations of GA. RelyX U200 (3M ESPE) and Panavia SA (Kuraray) were modified with 0.5 and 1 wt% GA. The setting time of five samples in each RC group was assessed using a thermocouple apparatus as described in the ISO 4049 test. Biaxial flexure strength was measured using a universal testing machine until failure. Vickers hardness was measured with three randomized indentations on the surface of each resin disc. RCs without GA were used as control. Data were analyzed using a one-way analysis of variance and Tukey's HSD test (α = 0.05). The setting times ranged from 2.4 to 4.6 min for RelyX and from 4.9 to 6.0 min for Panavia. The biaxial flexure strength ranged from 76.5 to 109.7 MPa for RelyX and from 73.3 to 108.2 MPa for Panavia. Vickers hardness values ranged from 41.6 to 58.6 for RelyX and 27.2 to 33.6 for Panavia. The addition of 0.5 and 1 wt% GA to improve durability of resin-dentin bonds had no adverse effects on setting time, whereas the biaxial flexure strength and Vickers hardness values for the tested materials were significantly reduced.

Study on commodity specification and grade standard and quality evaluation of Galla Chinensis / 中国中药杂志

This paper is aimed to study the commodity specification and grade standard of Galla Chinensis,for standardizing market order and guide the market circulation,and provide a basis for standardization of Galla Chinensis. With 33 samples of Galla Chinensis from market as the object of the research,the herbal textual research and market research were carried out. Then the grading indicator were selected by the descriptive statistics,principal component analysis and cluster analysis,combining with production practice,the commodity specification and grade standard of Galla Chinensis were set out. The data of moisture,ash,gallic acid as the internal index were used to analyze the relationship between the quality difference between grades and the appearance characters and the intrinsic composition. Herbal textual research and market research found that the high quality of Galla Chinensis characterized with large,complete,wall thick,grayish brown characteristics,and Galla Chinensis could be divided into gallnuts and horned gall. Through principal component analysis and cluster analysis,combining actual production and herbal record,screening,the length,diameter,single weight,the number of 500 g were determined as 4 grading indicators,the commodity specification was divided into two: gallnuts and horned gall,the grades was divided into two: selected goods and mixed goods. The result of correlation analysis showed there was no significant correlation between the internal index and the appearance characters of Galla Chinensis. The result of multiple comparison showed that the ash content of the selected goods was smaller than that of the mixed goods,but it did not reach significant. The content of gallic acid of the selected goods and the mixed goods of gallnuts were higher than selected goods of horned gall,and higher than mixed goods of horned galls. Using the length,diameter,single weight,the number of 500 g as the appearance characters index. Combining with the herbal textual research and market research,we have divided two specifications and two grades for the commodity specification and grade standard of Galla Chinensis,which can provide a basis for industry standards and national standards.

Antioxidant and growth inhibitory activities of Mesembryanthemum crystallinum L. in HCT116 human colon cancer cells / 한국영양학회지

PURPOSE: This study examined the antioxidant and cancer cell growth inhibitory activities of an ethanol extract and different solvent fractions of Mesembryanthemum crystallinum L. (ice plant). METHODS: The ice plant was freeze-dried, extracted with 99.9% ethanol, and then fractionated with hexane, ethyl acetate, butanol, and water. The total polyphenol content (TPC), total carotenoid content (TCC), 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity (RSA), and ferric reducing antioxidant power (FRAP) were measured. Assays using 2′,7′-dichlorofluorescin-diacetate and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide were performed to measure the intracellular reactive oxygen species (ROS) and cell growth, respectively. Annexin V/propidium iodide staining and cell cycle analysis were performed for the detection of apoptosis and cell cycle arrest. RESULTS: TPC, TCC, RSA, and FRAP of the ethanol extract (EE) were 3.7 mg gallic acid equivalent/g, 13.2 µg/g, 21.0% (at a concentration of 5 mg/mL), and 21.0% (at a concentration of 5 mg/mL), respectively. Among the different solvent fractions, the butanol fraction (BF) showed the highest TPC (5.4 mg gallic acid equivalent/g), TCC (86.6 µg/g), RSA (34.9% at 5 mg/mL), and FRAP (80.8% at 5 mg/mL). Treatment of HCT116 human colon cancer cells with EE and BF at concentrations of 250 and 500 µg/mL reduced the levels of intracellular ROS. Concomitantly, EE and BF resulted in the dose-dependent inhibition of cell growth (at the concentrations of 125, 250, and 500 µg/mL for 24 ~ 48 h) and the induction of apoptosis (at the concentrations of 250 and 500 µg/mL for 48 h) in HCT116 cells. An increased G2/M cell population was also found in the BF-treated cells. CONCLUSION: These results suggest that ice plant possesses antioxidant and growth inhibitory activities in colon cancer cells.

Carpinus turczaninowii extract modulates arterial inflammatory response: a potential therapeutic use for atherosclerosis

BACKGROUND/OBJECTIVES: Vascular inflammation is an important feature in the atherosclerotic process. Recent studies report that leaves and branches of Carpinus turczaninowii (C. turczaninowii) have antioxidant capacity and exert anti-inflammatory effects. However, no study has reported the regulatory effect of C. turczaninowii extract on the arterial inflammatory response. This study therefore investigated modulation of the arterial inflammatory response after exposure to C. turczaninowii extract, using human aortic vascular smooth muscle cells (HAoSMCs). MATERIALS/METHODS: Scavenging activity of free radicals, total phenolic content (TPC), cell viability, mRNA expressions, and secreted levels of cytokines were measured in LPS-stimulated (10 ng/mL) HAoSMCs treated with the C. turczaninowii extract. RESULTS: C. turczaninowii extract contains high amounts of TPC (225.6 ± 21.0 mg of gallic acid equivalents/g of the extract), as well as exerts time-and dose-dependent increases in strongly scavenged free radicals (average 14.8 ± 1.97 µg/mL IC50 at 40 min). Cell viabilities after exposure to the extracts (1 and 10 µg/mL) were similar to the viability of non-treated cells. Cytokine mRNA expressions were significantly suppressed by the extracts (1 and 10 µg/mL) at 6 hours (h) after exposure. Interleukin-6 secretion was dose-dependently suppressed 2 h after incubation with the extract, at 1–10 µg/mL in non-stimulated cells, and at 5 and 10 µg/mL in LPS-stimulated cells. Similar patterns were also observed at 24 h after incubation with the extract (at 1–10 µg/mL in non-stimulated cells, and at 10 µg/mL in the LPS-stimulated cells). Soluble intracellular vascular adhesion molecules (sICAM-1) secreted from non-stimulated cells and LPS-stimulated cells were similarly suppressed in a dose-dependent manner after 24 h exposure to the extracts, but not after 2 h. In addition, sICAM-1 concentration after 24 h treatment was positively related to IL-6 levels after 2 h and 24 h exposure (r = 0.418, P = 0.003, and r = 0.524, P < 0.001, respectively). CONCLUSIONS: This study demonstrates that C. turczaninowii modulates the arterial inflammatory response, and indicates the potential to be applied as a therapeutic use for atherosclerosis.

Active compounds and derivatives of camellia sinensis responding to erosive attacks on dentin

Abstract This research explored the potential of Camellia sinensis-derived teas and active compounds to be used as treatments to prevent dentin wear. Human root dentin slabs were randomly assigned to 5 groups (n = 10) as follows: distilled water (DW, control), epigallocatechin-3-gallate (EGCG), theaflavin gallate derivatives (TF), commercial green tea (GT), and commercial black tea (BT). The samples were submitted to a pellicle formation and an erosive cycling model (5x/day, demineralization using 0.01 M hydrochloric acid/60 s) followed by remineralization (human stimulated saliva/60 min) for three days. The samples were treated for 5 min using the test group solutions between the erosive cycles. Dentin changes were assessed with profilometry analysis and FT-Raman spectroscopy. The data regarding wear were analyzed by ANOVA followed by Tukey's test (p < 0.05). EGCG, TF derivatives, and both regular teas significantly suppressed erosive dentin loss (38-47%, p < 0.05). No obvious changes in the Raman spectra were detected in the specimens; however, the DW group had a minor relationship of 2880/2940 cm−1. The phenolic contents in both green and black tea and the important catechins appear to have protective effects on dentin loss.

Nematicidal Compounds from the Leaves of Schinus terebinthifolius Against Root-knot Nematode, Meloidogyne incognita Infecting Tomato

The root-knot nematode, Meloidogyne incognita caused a serious damage to many plants. The phenolic components of the leaves of Schinus terebinthifolius were investigated as potential nematicidal agents for M. incognita. Nine compounds were isolated and characterized as viz., 1,2,3,4,6-pentagalloyl glucose (1), kaempferol-3-O-α-L-rhamnoside (Afzelin) (2), quercetin-3-O-α-L-rhamnoside (Quercetrin) (3), myricetin (4), myricetin-3-O-α-L-rhamnoside (Myricetrin) (5), methylgallate (6), protocatechuic acid (7), quercetin (8), and gallic acid (9) using nuclear magnetic resonance (NMR) spectroscopy. Compound 1 showed pronounced nematicidal activity compared to Oxamyl as a positive control. It showed the lowest eggs-hatchability (34%) and the highest mortality in nematode population (21% after 72 hours of treatment) at a concentration of 200 µg/mL. It exhibited the best suppressed total nematode population, root galling and number of eggmasses in infected tomato plants. The total carbohydrates and proteins were also significantly induced by 1 with reduction in total phenolics and increase in defense-related proteins. Thus, compound 1 could be a promising, more safe and effective natural nematicidal agent for the control of root-knot nematodes.

Interaction between ascorbic acid and gallic acid in a model of fructose-mediated protein glycation and oxidation

Background: Dietary plant-based foods contain combinations of various bioactive compounds such as phytochemical compounds and vitamins. The combined effect of these vitamins and phytochemicals remains unknown, especially in the prevention of diabetes and its complications. The present study aimed to investigate the combined effect of ascorbic acid and gallic acid on fructose-induced protein glycation and oxidation. Results: Ascorbic acid (15 µg/mL) and gallic acid (0.1 µg/mL) reduced fructose-induced formation of advanced glycation end products (AGEs) in bovine serum albumin (BSA; 10 mg/mL) by 15.06% and 37.83%, respectively. The combination of ascorbic acid and gallic acid demonstrated additive inhibition on the formation of AGEs after 2 weeks of incubation. In addition, synergistic inhibition on the formation of amyloid cross-ß structure and protein carbonyl content in fructose-glycated BSA was observed. At the same concentration, the combination of ascorbic acid and gallic acid produced a significant additive effect on the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity. Conclusion: Combining natural compounds such as ascorbic acid and gallic acid seems to be a promising strategy to prevent the formation of AGEs.

Mistura de Ácido Gálico e Ciclosporina e seus Efeitos sobre a Disfunção Cardíaca Induzida pela Isquemia / Reperfusão e Expressão de eNOS/iNOS / Gallic Acid and Cyclosporine Mixture and their Effects on Cardiac Dysfunction Induced by Ischemia/Reperfusion and eNOS/iNOS Expression

Fundamento: Embora muitas pesquisas tenham sido conduzidas com um determinado antioxidante ou mPTP individualmente, pouca atenção tem sido dada para os efeitos da co-administração de um antioxidante e um inibidor de mPTP sobre a disfunção cardíaca após a lesão de I/R. Objetivos: Este estudo objetiva determinar os efeitos do ácido gálico (como antioxidante) combinado com a ciclosporina A (CsA) (como inibidor de mPTP) na função cardíaca e endotelial na disfunção induzida por I/R (função de NO). Métodos: Ratos Wistar machos foram pré-tratados com ácido gálico (7,5, 15 ou 30 mg.kg-1 de peso corporal, diariamente) por um período de 10 dias. Em seguida, o coração foi isolado e exposto a isquemia de 30 minutos e perfundido por CsA (0,2 µM) 20 min durante o período de reperfusão. Resultados: Os dados mostraram que o tamanho do infarto foi significativamente diminuído por CsA e ácido gálico sozinho (p < 0,05, ANOVA unidirecional seguido de teste LSD). A combinação de ambos os fármacos, entretanto, apresentou efeitos de melhora mais significativos (p < 0,001). A combinação destes dois fármacos melhorou mais significativamente a taxa máxima de aumento e de queda da pressão ventricular (± dp.dt-1 máx), o duplo produto (DP), a pressão ventricular esquerda desenvolvida (PVED), a frequência cardíaca e o fluxo coronário quando comparada à aplicação de apenas um deles (p < 0,05, medidas repetidas ANOVA seguidas de teste de LSD). Conclusões: Em conclusão, o benefício de um antioxidante concomitante com um inibidor da mPTP poderia ter efeitos mais benéficos sobre a disfunção cardíaca induzida pela lesão I/R

Background: Although many researches have been conducted on either a certain antioxidant or mPTP individually, little attention has been drawn to the effects of co-administration of an antioxidant and mPTP inhibitor together on cardiac dysfunction after I/R injury. Objectives: This study aims at determining the effects of gallic acid (as Antioxidant) combined with cyclosporine A (CsA) (as mPTP inhibitor) on I/R induced cardiac and endothelial (role of NO) dysfunction. Methods: Male Wistar rats were pretreated with gallic acid (7.5, 15, or 30mg.kg-1 body weight, daily) for a period of 10 days. Then, the heart was isolated and exposed to 30-minute ischemia and perfused by CsA (0.2 µM) 20 min during reperfusion period. Results: The data have shown that infarct size was decreased significantly by CsA and gallic acid alone (p < 0.05, one way ANOVA followed by LSD test), however the combination of both drugs had more significant improving effects (p < 0.001). The combination of these two drugs improved more significantly maximum rate of rise and fall of ventricular pressure (±dp.dt-1 max), rate pressure product (RPP), left ventricular developed pressure (LVDP), heart rate and coronary flow rather than applying each one alone (p < 0.05, repeated measurement ANOVA followed by LSD test). Conclusion: In conclusion, benefiting from an antioxidant concomitant with an mPTP inhibitor could have more improving effects on the cardiac dysfunction induced by I/R injury

Neuroprotective effects of Momordica charantia extract against hydrogen peroxide-induced cytotoxicity in human neuroblastoma SK-N-MC cells / 한국영양학회지

PURPOSE: Many studies have suggested that neuronal cells protect against oxidative stress-induced apoptotic cell death by polyphenolic compounds. We investigated the neuroprotective effects and the mechanism of action of Momordica charantia ethanol extract (MCE) against H₂O₂-induced cell death of human neuroblastoma SK-N-MC cells. METHODS: The antioxidant activity of MCE was measured by the quantity of total phenolic acid compounds (TPC), quantity of total flavonoid compounds (TFC), and 2,2-Diphenyl-1-pycrylhydrazyl (DPPH) radical scavenging activity. Cytotoxicity and cell viability were determined by CCK-8 assay. The formation of reactive oxygen species (ROS) was measured using 2,7-dichlorofluorescein diacetate (DCF-DA) assay. Antioxidant enzyme (SOD-1,2 and GPx-1) expression was determined by real-time PCR. Mitogen-activated protein kinases (MAPK) pathway and apoptosis signal expression was measured by Western blotting. RESULTS: The TPC and TFC quantities of MCE were 28.51 mg gallic acid equivalents/extract g and 3.95 mg catechin equivalents/extract g, respectively. The IC₅₀ value for DPPH radical scavenging activity was 506.95 µg/ml for MCE. Pre-treatment with MCE showed protective effects against H₂O₂-induced cell death and inhibited ROS generation by oxidative stress. SOD-1,2 and GPx-1 mRNA expression was recovered by pre-treatment with MCE compared with the presence of H₂O₂. Pre-treatment with MCE inhibited phosphorylation of p38 and the JNK pathway and down-regulated cleaved caspase-3 and cleaved PARP by H₂O₂. CONCLUSION: The neuroprotective effects of MCE in terms of recovery of antioxidant enzyme gene expression, down-regulation of MAPK pathways, and inhibition apoptosis is associated with reduced oxidative stress in SK-N-MC cells.

Identificación de ácidos polifenólicos en el extracto metanólico de las hojas de terminalia catappa Linn / Identification of polyphenolic acids in the methanolic extract from Terminalia catappa Linn leaves

INTRODUCCIÓN: diferentes extractos de Terminalia Catappa Linn. (Combretaceae) han demostrado de forma internacional, propiedades farmacológicas beneficiosas para la salud humana. Estas propiedades han sido atribuidas en lo fundamental a los polifenoles y glicósidos, encontrados en hojas, corteza y frutos. En Cuba esta especie es catalogada como una planta invasora y existen pocas investigaciones sobre su composición química y estudios farmacológicos. OBJETIVOS: identificar y cuantificar los ácidos polifenólicos presentes en el extracto metanólico de las hojas de T. catappa utilizándose la cromatografía de gases acoplada a espectrometría de masas. MÉTODOS: las hojas amarillo-rojizas fueron secadas, molidas, desgrasadas con hexano y y con posterioridad extraídas con metanol en un baño ultrasónico. El extracto se filtró y el disolvente se eliminó al vacío. El extracto seco se hidrolizó con ácido clorhídrico y se extrajo con acetato de etilo. Se determinó el rendimiento de extracción, las características organolépticas y los polifenoles totales mediante el método de Follin-Ciocalteu. La composición química del extracto hidrolizado se llevó a cabo por cromatografía de gases acoplada a espectrometría de masas, previa formación de los derivados trimetilsilil. RESULTADOS: se obtuvo un líquido de color pardo rojizo oscuro de olor característico. El contenido total de polifenoles fue 184,6 (mg Pirogalol/100 g Extracto). Se detectaron 37 compuestos por cromatografía de gases acoplada a espectrometría de masas en el extracto metanólico hidrolizado. Este extracto está compuesto de manera general por ácidos polifenólicos como el ácido gálico; ácido vanílico; ácido 3,4-dihidroxibenzoico; ácido 2,5-dihidroxi-benzoico y ácido 4- hidroxibenzoico. También se detectaron otros compuestos con elevados contenidos como ácido elágico y ácido levulínico. CONCLUSIONES: el extracto metanólico de hojas de T. catappa que crece en Cuba mostró un elevado contenido de ácidos polifenólicos, donde los ácidos gálico y elágico fueron los mayoritarios. La presencia de estos compuestos pudiera justificar las propiedades medicinales atribuidas a esta especie, a la vez que servirían de base para continuar con futuras pruebas farmacológicas que avalen sus usos con fines farmacéuticos.

INTRODUCTION: Different extracts of Terminalia Catappa Linn. (Combretaceae) internationally have shown pharmacological properties beneficial to human health. These properties have been largely attributed to polyphenols and their glycosides found in the leaves, bark and fruits. In Cuba this species is listed as an invasive plant and there is limited research on its chemical composition and pharmacological studies. OBJECTIVES: To identify and quantify the polyphenolic acids that could be present in the methanol extract of Terminalia catappa leaves using gas chromatography-mass spectrometry. METHODS: The yellow-red leaves were dried, ground, defatted with hexane and then extracted with methanol in an ultrasonic bath. The extract was filtered and the solvent removed under vacuum. The dry extract was hydrolyzed with hydrochloric acid and extracted with ethyl acetate. The extraction yield, the organoleptic characteristics and the total polyphenols by Follin-Ciocalteu method were determined. The chemical composition of the hydrolyzed extract was performed by gas chromatography-mass spectrometry after formation of trimethylsilyl derivatives. RESULTS: A dark reddish brown liquid with a characteristic odor was obtained. The total polyphenol content was 184.6 (mg Pyrogallol/100g extract). By mean of gas chromatography-mass spectrometry a total of 37 compounds were detected in the hydrolyzed methanol extract. This extract consists mainly of polyphenolic acids such as gallic acid; vanillic acid; 3,4-dihydroxybenzoic acid; 2,5-dihydroxybenzoic acid and 4- hydroxybenzoic acid. Other compounds with high content as ellagic acid and levulinic acid were also detected. CONCLUSIONS: The methanolic extract obtained from the leaves of Terminalia catappa growing in Cuba showed a high content of polyphenolic acids where gallic acid and ellagic predominated. The presence of these compounds could justify the medicinal properties attributed to this species, while providing the basis for further future pharmacological evidence to support its use for pharmaceutical purposes.

Experimental study on the effects of bismuth subgallate on the inflammatory process and angiogenesis of the oral mucosa / Estudo experimental sobre os efeitos do subgalato de bismuto no processo inflamatório e de angiogênese em mucosa bucal

ABSTRACT INTRODUCTION: Bismuth subgallate is a salt derived from heavy metal. The aim of this study was to evaluate the effect of this salt on some phases of healing. OBJECTIVES: To assess the effect of subgallate on mucosa and to evaluate the association between the use of bismuth subgallate and neogenesis of vessels in oral mucosal wounds. METHODS: This was a prospective and experimental study. This study used sixty rats, which were divided into control and experimental groups. The animals were submitted to a surgical procedure, which caused oral mucosal injury. A saline solution was applied on the wound of the control group, and in the experimental group, a solution of bismuth subgallate was administrated. RESULTS: The experimental group showed greater inflammatory reaction with increasing monomorphic proliferation. There was increased vessel proliferation in the control group. CONCLUSION: Bismuth subgallate had a negative influence on the healing process, delaying the rate of new vessel formation and optimal wound healing.

RESUMO INTRODUÇÃO: O subgalato de bismuto é um sal derivado de metal pesado. A ideia desta pesquisa é avaliar sua interferência em alguma das fases da cicatrização. OBJETIVO: Delinear a ação do subgalato em mucosas. Avaliar a relação entre a utilização do subgalato de bismuto e a neoformação de vasos nas feridas em mucosa oral, para evidenciar o possível benefício resultante do seu uso. MÉTODO: Estudo experimental, prospectivo. Utilizou-se sessenta ratos, que foram divididos igualmente em grupo controle e experimento. Foram submetidos a um procedimento cirúrgico onde foi feito uma lesão na mucosa oral dos animais, após, uma solução de soro fisiológico foi aplicada sobre a lesão do grupo controle e sobre a ferida do grupo experimento foi aplicada uma solução de subgalato de bismuto. RESULTADOS: o grupo experimento apresentou maior reação inflamatória com crescente proliferação monomórfica. Vasos: houve maior proliferação no grupo controle. CONCLUSÕES: concluiu-se que o subgalato de bismuto teve uma ação negativa no processo de cicatrização, atrasando a velocidade de formação dos neovasos e a cicatrização ideal da ferida operatória.

Effect of Gallic acid on dementia type of Alzheimer disease in rats: electrophysiological and histological studies

Introduction: To study the effect of gallic acid [GA] on hippocampal long-term potentiation [LTP] and histological changes in animal model of Alzheimer disease [AD] induced by beta-amyloid [Abeta]

Methods: Sixty-four adult male Wistar rats [300 +/- 20 g] were divided into 8 groups: 1] Control [Cont]; 2] AD; 3] Sham; 4-7] AD+GA [50, 100, and 200 mg/kg for 10 days, orally] or vehicle, 8] Cont+GA100, Abeta [1microg/microL in each site] was infused into hippocampus bilaterally. Changes of amplitude and slope of LTP induced in hippocampal dentate gyrus [DG] were evaluated by high frequency stimulation [HFS] of perforant path [PP]

Results: Data showed that LTP amplitude and area under curve significantly impaired in AD rats [P<0.001], while significantly improved in AD rats treated with GA [P<0.05, P<0.01]

Conclusion: Current findings suggest that GA reduces neural damage and brain amyloid neuropathology and improves cognitive function via free radicals scavenging and inhibiting oligomerization of Abeta but with no effect on healthy rats