RESUMEN
Biofilms, which consist of microorganisms embedded in a polymer-rich matrix, contribute to a variety of infections and increase antimicrobial resistance. Thus, there is a constant need to develop new chemotherapeutic agents to combat biofilms. This review article focuses on the use of alkyl gallates, gallic acid and its esters (methyl, ethyl, propyl, butyl, hexyl, octyl, and dodecyl gallate), most of which are found in plants, to inhibit biofilm formation. The studies under review reveal that alkyl gallates have the capacity to prevent biofilm development and eradicate mature biofilms through mechanisms that suppress the synthesis of the extracellular polymeric matrix, inhibit quorum-sensing signaling, and alter the microbial cell membrane. The effects are stronger the greater the length of the alkyl chain. Moreover, the alkyl gallates' preventive activity against biofilm formation occurs at doses below the minimum inhibitory concentration. More importantly, combining alkyl gallates with antimicrobials or blue-light irradiation produces a synergistic effect on the inhibition of biofilm formation that can be used to treat infections and overcome microbial resistance.
Asunto(s)
Antibacterianos , Ácido Gálico , Ácido Gálico/farmacología , Antibacterianos/farmacología , Percepción de Quorum , BiopelículasRESUMEN
A novel conjugate of docetaxel and biotin (designated as IDD-1010) was designed and chemically synthesized via an ester linkage at position 2' carbon in docetaxel. The synthesized pure IDD-1010 exhibits a potent anti-cancer activity in in vitro and in vivo studies. At 10 nM, IDD-1010 has induced increased apoptosis and mitotic arrest of PC3-Luc prostate cancer cells, causing aneuploidy and cell death at higher concentrations. Toxicology studies indicate that the maximal tolerated dose (MTD) of IDD-1010 is 150 mg/kg in mice; equivalent to about 12.2 mg/kg of body weight, or to about an 850 mg dose for a patient weighing 70 kg. The MTD-treated mice exhibited weight gain similar to that of the control group, with no gross pathological signs at 14 days post-dosing. At a lower dose, IDD-1010 treatment did not lead to any significant weight loss in mice, although decreased the tumor volume stemming from injecting cancer cells into the dorsal loop of mouse prostate, and it was found to be more potent than Paclitaxel (reference drug). Similarly, IDD-1010 treatment significantly reduced tumor weight and thereby increased the percentage of mice survival as compared to reference drug-treated and control groups. To summarize, the described experiments using IDD-1010, as compared to the reference drug, strongly suggest a potential treatment utility with a wider therapeutic window for prostate cancer. Henceforth, clinical research on such a novel drug candidate would be greatly worthwhile.
Asunto(s)
Antineoplásicos/farmacología , Biotina/química , Docetaxel/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Animales , Antineoplásicos/química , Apoptosis , Proliferación Celular , Docetaxel/química , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The accumulation of biofilm by Streptococcus mutans bacteria on hard tooth tissues leads to dental caries, which remains one of the most prevalent oral diseases. Hence, the development of new antibiofilm agents is of critical importance. The current study reports the results from testing the effectiveness of octyl gallate (C8-OG) against: (1) S. mutans biofilm formation on solid surfaces (polystyrene, glass), (2) acidogenicity, (3) and the expression of biofilm-related genes. The amount of biofilm formed by S. mutans bacteria was evaluated using the colorimetric method and optical profilometry. The pH of the biofilm growth medium was measured with microelectrode. A quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to assess the expression of genes encoding glucan binding protein B (gbpB), glucosyltransferases B, -C, -D (gtfB, -C, -D), and the F-ATPase ß subunit of the F1 protein (atpD). The results show that C8-OG significantly diminished biofilm formation by exposed S. mutans on solid surfaces and suppressed acidogenicity in a dose-dependent manner, compared to unexposed bacteria (p < 0.05). The C8-OG concentration of 100.24 µM inhibited S. mutans biofilm development on solid surfaces by 100% and prevented a decrease in pH levels by 99%. In addition, the RT-qPCR data demonstrate that the biofilm-producing bacteria treated with C8-OG underwent a significant reduction in gene expression in the case of the four genes under study (gbpB, gtfC, gtfD, and atpD), and there was a slight decrease in expression of the gtfB gene. However, C8-OG treatments did not produce significant expression change compared to the control for the planktonic cells, although there was a significant increase for the atpD gene. Therefore, C8-OG might be a potent antibiofilm and/or anticaries agent for oral formulations that aim to reduce the prevalence of dental caries.
Asunto(s)
Ácidos/metabolismo , Biopelículas/efectos de los fármacos , Ácido Gálico/análogos & derivados , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Streptococcus mutans/genética , Streptococcus mutans/fisiología , Antibacterianos/farmacología , Biomasa , Ácido Gálico/química , Ácido Gálico/farmacología , Genes Bacterianos , Vidrio/química , Poliestirenos/química , Streptococcus mutans/efectos de los fármacos , Propiedades de SuperficieRESUMEN
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.
Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/genética , Biopelículas/efectos de los fármacos , Ácido Gálico/análogos & derivados , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Streptococcus mutans/efectos de los fármacos , Adhesión Bacteriana/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Biopelículas/crecimiento & desarrollo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Medios de Cultivo/química , Caries Dental/microbiología , Caries Dental/prevención & control , Relación Dosis-Respuesta a Droga , Ácido Gálico/farmacología , Vidrio/química , Glucosiltransferasas/genética , Glucosiltransferasas/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Lectinas/genética , Lectinas/metabolismo , Pruebas de Sensibilidad Microbiana , Poliestirenos/química , ATPasas de Translocación de Protón/genética , ATPasas de Translocación de Protón/metabolismo , Streptococcus mutans/genética , Streptococcus mutans/crecimiento & desarrollo , Streptococcus mutans/metabolismoRESUMEN
OBJECTIVES: The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs. MATERIALS: A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes. METHOD: The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules. RESULTS: By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab. CONCLUSION: The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.
Asunto(s)
Antiinflamatorios/clasificación , Productos Biológicos/clasificación , Modelos Teóricos , Fitoquímicos/clasificación , Antiinflamatorios/química , Productos Biológicos/química , Fitoquímicos/químicaRESUMEN
OBJECTIVES: The aim was to evaluate the activity of seven medicinal, anti-inflammatory plants at the hH4R with focus on defined chemical compounds from Curcuma longa. MATERIALS: Activities were analyzed with membrane preparations from Sf9 cells, transiently expressing the hH4R, Gαi2 and Gß1γ2 subunits. METHODS: From the methanolic extract of C. longa curcumin (1), demethoxycurcumin (2) and bis(4-hydroxy-cinnamoyl)methane (3) were isolated, purified with HPLC (elution-time 10.20, 9.66, 9.20 min, respectively) and together with six additional extracts, were characterized via radioligand binding studies at the hH4R. RESULTS: Compounds from C. longa were the most potent ligands at the hH4R. They exhibited estimated K i values of 4.26-6.26 µM (1.57-2.31 µg/mL) (1); 6.66--8.97 µM (2.26-3.04 µg/mL) (2) and 10.24-14.57 µM (3.16-4.49 µg/mL) (3) (95% CI). The estimated K i value of the crude extract of curcuma was 0.50-0.81 µg/mL. Fractionated curcumin and the crude extract surpassed the effect of pure curcumin with a K i value of 5.54 µM or 2.04 µg/mL [95% CI (4.47-6.86 µM), (1.65-2.53 µg/mL)]. CONCLUSION: Within this study, defined compounds of C. longa were recognized as potential ligands and reasonable lead structures at the hH4R. The mode of anti-inflammatory action of curcumin was further elucidated and the role of extracts in traditional phytomedicine was strengthened.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Curcuma/química , Extractos Vegetales/farmacología , Receptores Histamínicos H4/efectos de los fármacos , Unión Competitiva/efectos de los fármacos , Línea Celular , Membrana Celular/efectos de los fármacos , Curcumina/análogos & derivados , Curcumina/química , Curcumina/farmacología , Diarilheptanoides , Relación Dosis-Respuesta a Droga , Humanos , Extractos Vegetales/química , Plantas Medicinales , Ensayo de Unión RadioliganteRESUMEN
Based on DFT, MP2, and the density functional from Truhlar group (hybrid GGA: MPW1k) calculations for an acid-catalyzed hydrolysis of nine Kirby's N-alkylmaleamic acids and two atenolol prodrugs were designed. The calculations demonstrated that the amide bond cleavage is due to intramolecular nucleophilic catalysis by the adjacent carboxylic acid group and the rate-limiting step is determined based on the nature of the amine leaving group. In addition, a linear correlation of the calculated and experimental rate values has drawn credible basis for designing atenolol prodrugs that are bitterless, are stable in neutral aqueous solutions, and have the potential to release the parent drug in a sustained release manner. For example, based on the calculated B3LYP/6-31 G (d,p) rates, the predicted t1/2 (a time needed for 50% of the prodrug to be converted into drug) values for atenolol prodrugs ProD 1-ProD 2 at pH 2 were 65.3 hours (6.3 hours as calculated by GGA: MPW1K) and 11.8 minutes, respectively. In vitro kinetic study of atenolol prodrug ProD 1 demonstrated that the t1/2 was largely affected by the pH of the medium. The determined t1/2 values in 1N HCl, buffer pH2, and buffer pH 5 were 2.53, 3.82, and 133 hours, respectively.
Asunto(s)
Atenolol/química , Profármacos/química , Atenolol/síntesis química , Química Farmacéutica , Diseño de Fármacos , Hidrólisis , Cinética , Estructura Molecular , Profármacos/síntesis químicaRESUMEN
Based on density functional theory (DFT) calculations for the acid-catalyzed hydrolysis of several maleamic acid amide derivatives four tranexamic acid prodrugs were designed. The DFT results on the acid catalyzed hydrolysis revealed that the reaction rate-limiting step is determined on the nature of the amine leaving group. When the amine leaving group was a primary amine or tranexamic acid moiety, the tetrahedral intermediate collapse was the rate-limiting step, whereas in the cases by which the amine leaving group was aciclovir or cefuroxime the rate-limiting step was the tetrahedral intermediate formation. The linear correlation between the calculated DFT and experimental rates for N-methylmaleamic acids 1-7 provided a credible basis for designing tranexamic acid prodrugs that have the potential to release the parent drug in a sustained release fashion. For example, based on the calculated B3LYP/6-31G(d,p) rates the predicted t1/2 (a time needed for 50 % of the prodrug to be converted into drug) values for tranexamic acid prodrugs ProD 1-ProD 4 at pH 2 were 556 h [50.5 h as calculated by B3LYP/311+G(d,p)] and 6.2 h as calculated by GGA: MPW1K), 253 h, 70 s and 1.7 h, respectively. Kinetic study on the interconversion of the newly synthesized tranexamic acid prodrug ProD 1 revealed that the t1/2 for its conversion to the parent drug was largely affected by the pH of the medium. The experimental t1/2 values in 1 N HCl, buffer pH 2 and buffer pH 5 were 54 min, 23.9 and 270 h, respectively.
Asunto(s)
Hemorragia/tratamiento farmacológico , Profármacos/síntesis química , Ácido Tranexámico/síntesis química , Diseño de Fármacos , Hemorragia/patología , Humanos , Concentración de Iones de Hidrógeno , Hidrólisis , Cinética , Profármacos/farmacocinética , Ácido Tranexámico/farmacocinéticaRESUMEN
Screening of phytochemical Ephedra alte crude extract by GC-MS and HPLC analysis indicated the presence of alkaloids, tannins, flavonoids, terpenoids, and phenolic acid in the extract. The total phenolic content of E. alte methanol extract was 39.43 mg of Gallic acid eq/g, crude E. alte with 56.74, and 2.42 µg Trolox equivalent antioxidant capacity (TEAC)/g of plant extract according to DPPH and FRAP assay, respectively. The antimicrobial activity of E. alte against Staphylococcus aureus, staphylococcus epidermidis, Escherichia coli, and Klebsiellaoxytoca demonstrated a mean zone diameter of inhibition ranging from 0 to 17 mm. The MIC of the extracts ranged from 0.5 to 1.0 mg/mL. E. alte extract inhibits pepsin enzyme activity with IC50 values of 213.67 µg/ml. This study revealed that E. alte extract has pepsin enzyme inhibitory, antibacterial, antioxidant activities. The current outcomes indicate that E. alte might be employed as a natural agent for managing GERD and infectious diseases.
RESUMEN
Artichoke-like wild thistles are often used in Palestinian cuisine. One of the most commercially recognized species of these wild edible thistles is Gundelia tournefortii, a common plant in the Mediterranean region. G. tournefortii, or 'Akoob' in Arabic, remains uncultivated, harvested wild by local populations and considered highly valuable due to its reputed health benefits. The present study aimed to investigate the anticancer effects of G. tournefortii on the human colon carcinoma HCT-116 cell line. Methanol and hexane extracts were identified to exert considerable antitumor activity against the HCT-116 cancer cell line, while the aqueous extract was inactive. The phytochemical profiles of the methanol and hexane extracts were investigated using gas chromatography-mass spectrometry. A total of 6 of the 27 natural compounds identified, including sitosterol, stigmasterol, lupeol, gitoxigenin, α-amyrin and artemisinin, have been previously validated as being active against cancerous cells. Therefore, the presence of these phytochemicals in G. tournefortii is of importance in its role in preventing and treating cancer.
RESUMEN
BACKGROUND: A considerable worldwide increase in the rate of invasive fungal infections and resistance toward antifungal drugs was witnessed during the past few decades. Therefore, the need for newer antifungal candidates is paramount. Nature has been the core source of therapeutics for thousands of years, and an impressive number of modern drugs including antifungals were derived from natural sources. In order to facilitate the recognition of potential candidates that can be derived from natural sources, an iterative stochastic elimination optimization technique to index natural products for their antifungal activity was utilized. METHODS: A set of 240 FDA-approved antifungal drugs, which represent the active domain, and a set of 2,892 natural products, which represent the inactive domain, were used to construct predictive models and to index natural products for their antifungal bioactivity. The area under the curve for the produced predictive model was 0.89. When applying it to a database that is composed of active/inactive chemicals, we succeeded to detect 42% of the actives (antifungal drugs) in the top one percent of the screened chemicals, compared with one-percent when using a random model. RESULTS AND CONCLUSION: Eight natural products, which were highly scored as likely antifungal drugs, are disclosed. Searching PubMed showed only one molecule (Flindersine) out of the eight that have been tested was reported as an antifungal. The other seven phytochemicals await evaluation for their antifungal bioactivity in a wet laboratory.
Asunto(s)
Antifúngicos/clasificación , Antifúngicos/farmacología , Productos Biológicos/clasificación , Productos Biológicos/farmacología , Algoritmos , Antifúngicos/química , Productos Biológicos/química , Bases de Datos FarmacéuticasRESUMEN
Background: The wild population of spotted golden thistle, Scolymus maculatus, which belongs to the Compositae family, is believed to be one of the multi-curative wild plants mentioned in Flora Palaestina. This study aims to disclose the phytochemical composition, antioxidant potential, and antimicrobial activity of wild S. maculatus collected from the farms of Kabul, a village in northwest Galilee, for the first time. Methods: The phytochemical components of crude S. maculatus extracts from methanol, ethyl acetate, and n-hexane solvents were separated and identified using gas chromatography-mass spectrometry (GC-MS) in the electron impact (EI) mode. The free radical scavenging of the plant extracts was measured by DPPH assay. The microdilution test was used to determine the minimum inhibitory concentrations (MICs) of different S. maculatus extracts and to evaluate their antimicrobial activities. Results: Thirty-two phytochemicals were found in S. maculatus extracts including stigmasterol, γ-sitosterol, lupeol, lupeol acetate, and ß-amyrin. Phytochemicals, such as 2-linoleoylglycerol, γ-sitosterol, ß-amyrin, lupeol, (3α)-12-oleanen-3-yl acetate, and lupenyl acetate, were found to dominate the methanol extract. Most of these compounds were also observed in ethyl acetate and n-hexane extracts, but at different levels, in addition to some other minor compounds. The various extracts were investigated for their antioxidant and antimicrobial activity. The ethanolic and the methanolic extracts were shown to exhibit the highest free radical scavenging by DPPH assay with a half-maximally effective concentration (EC50) of 0.37 and 0.65 mg/mL respectively, while the other three extracts (aqueous, ethyl acetate and n-hexane) were less active and their EC50 (effective concentration at which DPPH radical was scavenged by 50%) were above 1.0 mg/mL. Moreover, MICs were determined to be effective against Staphylococcus aureus, Salmonella typhimurium, and Candida albicans microorganisms. Ethyl acetate and the ethanolic extracts are active against the three types of microorganisms at a minimum inhibitory concentration (MIC) of 0.5 mg/mL, while aqueous and the n-hexane extracts are inactive against Salmonella typhimurium. Conclusions: The results show that S. maculatus extracts are a rich source of compounds that can play an important role in human health, and in a broader context, in the treatment of various diseases, such antimicrobial and antioxidant-related ailments.
RESUMEN
Majorana syriaca (Zaatar in Arabic), belonging to the mint family, Labiates, is cultivated widely and grows wild in the mountains of Palestine between the months April to August. In order to determine the secondary metabolites from wild leaves of Palestinian M. syriaca, comparative analysis by static headspace (HS) and steam distillation (SD) GC-MS was used. Among the samples examined, the major constituents identified varied greatly throughout the different harvesting periods. Headspace revealed major volatiles and semi-volatiles of alpha-pinene, beta-myrecene, o-cymene, p-cymene, gamma-terpinene, thymol, and carvacrol. We found that the most abundant monoterpenes, i.e. gamma-terpinene and p-cymene were decreased in the month of May since they are the biogenetic precursors (via enzymic hydroxylation) of the phenolic terpenes, thymol and carvacrol. The harvesting time, location and the thyme type (i.e., wild) affects the yield of essential oils as reflected by normal steam distillation.
Asunto(s)
Monoterpenos/metabolismo , Hojas de la Planta/química , Timol/metabolismo , Thymus (Planta)/química , Cimenos , Cromatografía de Gases y Espectrometría de Masas , Medio Oriente , Aceites Volátiles/análisisRESUMEN
The aim of this study is to disclose the potential bioactive components of Cuscuta palaestina, a native parasitic natural plant of flora palaestina and to open direction towards new prospective application. GC-MS analysis identified 18 components in the methanolic extract of C. palaestina for the first time. The most appealing among them are Sesamin and two other phytosterols (Campesterol and Stigmasterol), all of which are documented in the scientific literature for their anticancer activity. Quantitation of Sesamin extracted from C. palaestina by HPLC-PDA with the use of three organic solvents showed that the Sesamin content in the methanolic extract was the highest. Following the disclosure of Sesamin presence in C. palaestina, we raised the question of whether it is produced naturally in C. palaestina or acquired from the host plant. The quantitation of Sesamin in C. palaestina was performed while being with five different host plants, and was compared with the amount of Sesamin in C. palaestina grown alone. The findings reveal that Sesamin is an endogenous secondary metabolite in C. palaestina. Thus, further studies are required to prove if C. palaestina can be used as an alternative source of anticancer phytochemicals, mainly Sesamin, and if proteins in the Sesamin production pathway could be valid biological targets for the development of novel and selective pesticides for control/ eradication of C. palaestina and maybe some other Cuscuta species. As well, the findings from this study raise a big question of whether inferring Sesamin production in C. palaestina could reduce its attack ability to host plants.
Asunto(s)
Cuscuta/química , Dioxoles/química , Dioxoles/aislamiento & purificación , Lignanos/química , Lignanos/aislamiento & purificación , Calibración , Cuscuta/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Lignanos/biosíntesisRESUMEN
Background: The goals of the current study were to address a new concept termed a health benefits' index (HBI) and to verify the type of correlation between the pricing of honey and its HBI/medicinal properties. Diverse types of honey from different origins and places were investigated for their antioxidant and antimicrobial activity. Methods: We have utilized a modified protocol of the DPPH assay for measuring free radical scavenging and the microdilution test for the determination of antibacterial/antifungal minimum inhibitory concentrations (MICs). MICs were determined against Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and Candida albicans microorganisms. Employing a "combined benefits approach" enabled us to attach to each honey type a unique number of HBI that correlate with honey health and medicinal values. Results: The various types of honey demonstrated significant but variable antioxidant, antibacterial, and antifungal activities. Types of wildflower-labeled honey were found to have a wide range of HBI values and medicinal properties, probably due to their containing different nectar contents/phytochemicals. Moreover, an inconsiderable correlation was detected between the market prices of different types of honey and their HBIs. Conclusions: The proposed index of health benefits could be recalculated/updated following measurement of more and more medicinal properties, such as anti-inflammatory, antidiabetic, and anticancer activities. This index could be used as an effective tool for consumers of honey to evaluate the real value of the purchased product.
RESUMEN
BACKGROUND: A comparative analysis by using static headspace (HS) and steam distillation (SD) GC-MS of the volatile and the semi-volatile secondary metabolites from leaves of cultivated Majorana syriaca. METHODS: The essential oils endogenous to cultivated thyme were isolated and identified by HS-GC-MS technology and compared to those from SD-GC-MS. RESULTS: The HS-GC-MS results showed that the Palestinian cultivated thyme is rich in monoterpene hydrocarbons and phenolic monoterpenes such as alpha-phellandrene, alpha-pinene, beta-myrcene, m-cymene, p-cymene, gamma-terpinene, thymol and carvacrol. In all the samples gamma-terpinene, p-cymene, thymol and carvacrol were the most abundant compounds. CONCLUSIONS: HS and SD-GC-MS have proved that most of the cultivated thyme samples examined has thymol isomer as the major phenolic constituent.
Asunto(s)
Monoterpenos/análisis , Origanum/química , Timol/análisis , Thymus (Planta)/química , Cimenos , Cromatografía de Gases y Espectrometría de Masas , Medio Oriente , Hojas de la Planta/químicaRESUMEN
The production of olive oil generates massive quantities of by-product called olive mill wastewater (OMWW). The uncontrolled disposal of OMWW poses serious environmental problems. The OMWW effluent is rich in several polyphenolic compounds. Liquid-liquid extraction of OMWW using ethyl acetate solvent was used to enrich phenolic compounds under investigation. Total phenolic and flavonoid content and antioxidant activity of the extract were determined. HPLC coupled to photodiode array (PDA) detector was used to analyze the main three phenolic compounds of OMWW, namely, hydroxytyrosol, tyrosol, and oleuropein. The antimicrobial activity of the extract was also investigated. Additionally, the OMWW extract was used as natural preservative and antioxidants for olive oil. Results showed that OMWW is very rich in phenolic compounds and has strong antioxidant activity. HPLC analysis showed that the extract contains mainly hydroxytyrosol and tyrosol but no oleuropein. The OMWW extract showed also positive activities as antibacterial (gram positive and gram negative) and antifungal as well as activities against yeast. The addition of OMWW extract to olive oil samples has an effect on the stability of olive oil as reflected by its acid value, peroxide value, K232 and K270, and total phenolic content.
RESUMEN
BACKGROUND: Ephedra is among Palestinian medicinal plants that are traditionally used in folkloric medicine for treating many diseases. Ephedra is known to have antibacterial and antioxidant effects. The goal of this study is to evaluate the antioxidant activity of different extracts from the Ephedra alata plant growing wild in Palestine, and to analyze their phenolic and flavonoid constituents by HPLC/PDA and HPLC/MS. MATERIALS AND METHODS: Samples of the Ephedra alata plant grown wild in Palestine were extracted with three different solvents namely, 100% water, 80% ethanol, and 100% ethanol. The extracts were analyzed for their total phenolic content (TPC), total flavonoid content (TFC), antioxidant activity (AA), as well as phenolic and flavonoids content by HPLC/PDA/MS. RESULTS: The results revealed that the polarity of the extraction solvent affects the TPC, TFC, and AA of extracts. It was found that both TPC and AA are highest for plant extracted with 80% ethanol, followed by 100% ethanol, and finally with 100% water. TFC however was highest in the following order: 100% ethanol > 80% ethanol > water. Pearson correlation indicated that there is a significant correlation between AA and TPC, but there is no correlation between AA and TFC. Simultaneous HPLC-PDA and UHPLC-MS analysis of the ethanolic plant extracts revealed the presence of Luteolin-7-O-glucuronide flavone, Myricetin 3-rhamnoside and some other major polyphenolic compounds that share myricetin skeleton. CONCLUSION: Ephedra alata extract is rich in potent falvonoid glycosidic compounds as revealed by their similar overlaid UV-Vis spectra and UHPLC-MS results. On the basis of these findings, it is concluded that Ephedra alata constitutes a natural source of potent antioxidants that may prevent many diseases and could be potentially used in food, cosmetics, and pharmaceutical products.
Asunto(s)
Antioxidantes/farmacología , Ephedra/química , Flavonoides/farmacología , Fenoles/farmacología , Extractos Vegetales/farmacología , Antioxidantes/análisis , Cromatografía Líquida de Alta Presión , Flavonas/análisis , Flavonas/farmacología , Flavonoides/análisis , Glicósidos/análisis , Glicósidos/farmacología , Luteolina/análisis , Luteolina/farmacología , Espectrometría de Masas/métodos , Oxidación-Reducción , Fenoles/análisis , Extractos Vegetales/química , Polifenoles/análisis , Polifenoles/farmacología , SolventesRESUMEN
Modeling G-Protein Coupled Receptors (GPCRs) is an emergent field of research, since utility of high-quality models in receptor structure-based strategies might facilitate the discovery of interesting drug candidates. The findings from a quantitative analysis of eighteen resolved structures of rhodopsin family "A" receptors crystallized with antagonists and 153 pairs of structures are described. A strategy termed endeca-amino acids fragmentation was used to analyze the structures models aiming to detect the relationship between sequence identity and Root Mean Square Deviation (RMSD) at each trans-membrane-domain. Moreover, we have applied the leave-one-out strategy to study the shiftiness likelihood of the helices. The type of correlation between sequence identity and RMSD was studied using the aforementioned set receptors as representatives of membrane proteins and 98 serine proteases with 4753 pairs of structures as representatives of globular proteins. Data analysis using fragmentation strategy revealed that there is some extent of correlation between sequence identity and global RMSD of 11AA width windows. However, spatial conservation is not always close to the endoplasmic side as was reported before. A comparative study with globular proteins shows that GPCRs have higher standard deviation and higher slope in the graph with correlation between sequence identity and RMSD. The extracted information disclosed in this paper could be incorporated in the modeling protocols while using technique for model optimization and refinement.
Asunto(s)
Modelos Moleculares , Conformación Proteica , Rodopsina/química , Secuencia de Aminoácidos , Humanos , Simulación de Dinámica Molecular , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Receptores Acoplados a Proteínas G/química , Relación Estructura-ActividadRESUMEN
Streptococcus mutans (S. mutans) bacterium is the most well recognized pathogen involved in pathogenesis of dental caries. Its virulence arises from its ability to produce a biofilm and acidogenicity, causing tooth decay. Discovery of natural products capable to inhibit biofilm formation is of high importance for developing health care products. To the best of our knowledge, in all previous scientific reports, a colorimetric assay was applied to test the effect of sumac and methyl gallate (MG) on S. mutans adherence. Quantitative assessment of the developed biofilm should be further performed by applying an optical profilometry assay, and by testing the effect on both surface roughness and thickness parameters of the biofilm. To the best of our knowledge, this is the first study to report the effect of sumac extract and its constituent MG on biofilm formation using an optical profilometry assay. Testing antibacterial activity of the sumac extract and its fractions revealed that MG is the most bioactive component against S. mutans bacteria. It reduced S. mutans biofilm biomass on the polystyrene surface by 6893%, whereas 1 mg/ml MG was able to decrease the biofilm roughness and thickness on the glass surface by 99%. MG also prevented a decrease in pH level by 97%. These bioactivities of MG occurred in a dosedependent manner and were significant vs. untreated bacteria. The findings are important for the development of novel pharmaceuticals and formulations of natural products and extracts that possess antibiofilm activities with primary applications for oral health, and in a broader context, for the treatment of various bacterial infections.