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This study was designed to investigate chemical composition and biological activities of the Anthriscus cerefolium methanolic extract. Chemical characterization of the extracts was performed by LC-HRMS/MS analysis. Antimicrobial activities of the extract were investigated on six bacteria and eight fungi while antioxidant activity was assessed by six different assays. Anti-enzymatic activity of the methanolic extract was tested on five enzymes associated with therapy of neurodegenerative diseases and diabetes mellitus type 2. Cytotoxic properties of the extract were tested on human immortalized keratinocytes (HaCaT) and tumor cell lines (SiHa, MCF7, HepG2). Anti-inflammatory activity of the extract was assessed on bacteria mediated inflammation model using HaCaT cell line. Molecular docking studies of enzymes and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis were performed. The results showed that the obtained extract was rich in phenolic compounds (a total of seventy-two were identified), with malonyl-1,4-O-dicaffeoylquinic acid and 3,5-O-dicaffeoylquinic acid dominating in the sample. The extract expressed antimicrobial, antioxidant, anti-enzymatic, cytotoxic and anti-inflammatory properties. The identified compounds demonstrated strong binding to the acetylcholinesterase (AChE) and to a lesser extent, to the butyrylcholinesterase (BChE), glucosidase, amylase, and modestly, to tyrosinase. KEGG pathway analysis has shown that the certain phenolic compounds may be related to anti-tumor, anti-inflammatory and anti-microbial activities of the extract. The data obtained suggest that phenolic compounds of the extract and their mixtures should be considered for future research as ingredients in pharmaceutical and nutraceutical formulations.
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Antiinflamatorios , Antioxidantes , Simulación del Acoplamiento Molecular , Extractos Vegetales , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antioxidantes/farmacología , Antiinflamatorios/farmacología , Línea Celular Tumoral , Antiinfecciosos/farmacología , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Fenoles/farmacologíaRESUMEN
The present study was performed to determine the chemical constituents, cytotoxicity, antioxidant and enzyme inhibition activities of the aerial parts of Glaucium acutidentatum Hausskn. and Bornm. (family Papaveraceae). Methanolic and aqueous extracts were prepared by maceration, homogenizer-assisted extraction (HAE) and infusion. Results showed that the highest total phenolic and flavonoids contents were obtained from the methanol extracts obtained by HAE (53.22 ± 0.10 mg GAE/g) and maceration (30.28 ± 0.51 mg RE/g), respectively. The aporphine, beznyltetrahydroisoquinoline, and protopine types of Glaucium alkaloids have been tentatively identified. Among them, glaucine was identified in all extracts. Flavonoids, phenolic acids, coumarins, organic acids and fatty acids were also detected. Methanolic extract obtained using the HAE method displayed the highest anti-DPPH (41.42 ± 0.62 mg TE/g), total antioxidant (1.20 ± 0.17 mmol TE/g), Cu2+ (113.55 ± 6.44 mg TE/g), and Fe3+ (74.52 ± 4.74 mg TE/g) reducing properties. The aqueous extracts obtained by infusion and HAE methods exerted the best anti-ABTS (103.59 ± 1.49 mg TE/g) and chelating (19.81 ± 0.05 mg EDTAE/g) activities, respectively. Methanolic extract from HAE recorded the highest acetylcholinesterase (2.55 ± 0.10 mg GALAE/g) and α-amylase (0.51 ± 0.02 mmol ACAE/g) inhibition activities, while that obtained by maceration showed the best butyrylcholinesterase (3.76 ± 0.31 mg GALAE/g) inhibition activity. Both extracts revealed the best tyrosinase inhibitory activity (25.15 ± 1.00 and 26.79 ± 2.36 mg KAE/g, p ≥ 0.05). G. acutidentatum maceration-derived aqueous extract showed selective anticancer activity against cells originating from human hypopharyngeal carcinoma. In conclusion, these findings indicated that G. acutidentatum is a promising source of alkaloids and phenolic compounds for variable pharmaceutical formulations.
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Tanacetum nitens ( Boiss. & Noë) Grierson is an aromatic perennial herb used in Turkish traditional medicine to treat headache, fever, and skin diseases. This study aimed to investigate the chemical composition, antioxidant, enzyme inhibition, and cytotoxic properties of T. nitens aerial parts. Organic solvent extracts were prepared by sequential maceration in hexane, dichloromethane, ethyl acetate, and methanol while aqueous extracts were obtained by maceration or infusion. Nuclear magnetic resonance (NMR) and LC-DAD-MS analysis allowed the identification and quantification of different phytoconstituents including parthenolide, tanacetol B, tatridin B, quinic acid derivatives, ß-sitosterol, and glycoside derivatives of quercetin and luteolin. The type and amount of these phytochemicals recovered by each solvent were variable and significant enough to impact the biological activities of the plant. Methanolic and aqueous extracts displayed the highest scavenging and ions-reducing properties while the dichloromethane and ethyl acetate extracts exerted the best total antioxidant activity and metal chelating power. Results of enzyme inhibition activity showed that the hexane, ethyl acetate, and dichloromethane extracts had comparable anti-acetylcholinesterase activity and the latter extract revealed the highest anti-butyrylcholinesterase activity. The best α-amylase and α-glucosidase inhibition activities were obtained from the hexane extract. The dichloromethane and ethyl acetate extracts exhibited the highest cytotoxic effect against the prostate carcinoma DU-145 cells. In conclusion, these findings indicated that T. nitens can be a promising source of biomolecules with potential therapeutic applications.
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Benzene sulfonamides are an important biological substituent for several activities. In this study, hybridization of benzene sulfonamide with piperazine derivatives were investigated for their antioxidant capacity and enzyme inhibitory potencies. Six molecules were synthesized and characterized. DPPH, ABTS, FRAP, CUPRAC, chelating and phosphomolybdemum assays were applied to evaluate antioxidant capacities. Results show that compounds have high antioxidant capacity and compound 4 has the best antioxidant activity among them. Compound 4 has higher antioxidant activity than references for FRAP (IC50: 0.08â¯mM), CUPRAC (IC50: 0.21â¯mM) and phosphomolybdenum (IC50: 0.22â¯mM) assays. Besides this, compound 4 has moderate DPPH and ABTS antioxidant capacity. Furthermore, enzyme inhibition activities of these molecules were investigated against AChE, BChE, tyrosinase, α-amylase and α-glucosidase enzymes. It was revealed that all compounds have good enzyme inhibitory potential except for α-amylase enzyme. The best inhibitory activities were observed for AChE with compound 5 the same value (IC50: 1.003â¯mM), for BChE with compounds 2 and 5 the same value (IC50: 1.008â¯mM), for tyrosinase compound 4 (IC50: 1.19â¯mM), and for α-glucosidase with compound 3 (IC50: 1.000â¯mM). Docking studies have been conducted with these molecules, and the results correlate well with the inhibitory assays.
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Aim: A highly efficient one-step method has been developed for the synthesis of benzofuranyl derivatives from 2-benzoylcyclohexane-1-carboxylic acid derivatives using chlorosulfonyl isocyanate. This novel method provides a practical, cost-effective and efficient approach. Materials & methods: The inhibitory effects of benzofuranyl derivatives on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were investigated. Ki values were determined to range from 0.009 to 0.61 µM for AChE and 0.28 to 1.60 µM for BChE. Molecular docking analysis provided insights into the interaction modes and binding patterns of these compounds with AChE and BChE. Conclusion: Kinetic findings of our study suggest that some of our compounds exhibited more effective low micromolar inhibition compared with the reference, and these derivatives could be used to design more powerful agents.
[Box: see text].
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Acetilcolinesterasa , Benzofuranos , Butirilcolinesterasa , Inhibidores de la Colinesterasa , Simulación del Acoplamiento Molecular , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/síntesis química , Acetilcolinesterasa/metabolismo , Acetilcolinesterasa/química , Benzofuranos/química , Benzofuranos/farmacología , Benzofuranos/síntesis química , Humanos , Relación Estructura-Actividad , Cinética , Estructura MolecularRESUMEN
The present study aimed to investigate the chemical profile, antioxidant, and enzyme inhibition properties of extracts from fruits and aerial parts (leaves and twigs) of Tamarix aphylla and T. senegalensis. Hexane, dichloromethane, ethyl acetate (EtOAc), and methanol extracts were prepared sequentially by maceration. Results revealed that EtOAc extracts of T. senegalensis and T. aphylla fruits contained the highest total phenolic content (113.74 and 111.21 mg GAE/g) while that of T. senegalensis (38.47 mg RE/g) recorded the highest total flavonoids content. Among the quantified compounds; ellagic, gallic, 3-hydroxybenzoic, caffeic, syringic, p-coumaric acids, isorhamnetin, procyanidin B2, and kaempferol were the most abundant compounds in the two species. EtOAc extracts of the two organs of T. senegalensis in addition to MeOH extract of T. aphylla aerial parts displayed the highest chelating power (21.00-21.30 mg EDTAE/g, p > 0.05). The highest anti-AChE (3.11 mg GALAE/g) and anti-BChE (3.62 mg GALAE/g) activities were recorded from the hexane and EtOAc extracts of T. senegalensis aerial parts and fruits, respectively. EtOAc extracts of the fruits of the two species exerted the highest anti-tyrosinase (anti-Tyr) activity (99.44 and 98.65 mg KAE/g, p > 0.05). Also, the EtOAc extracts of the both organs of the two species exhibited highest anti-glucosidase activity (0.88-0.90 mmol ACAE/g, p > 0.05) while the best anti-α-amylase activity was recorded from the dichloromethane extract of T. senegalensis fruits (0.74 mmol ACAE/g). In this study, network pharmacology was employed to examine the connection between compounds from Tamarix and their potential effectiveness against Alzheimer's disease. The compounds demonstrated potential interactions with pivotal genes including APP, GSK3B, and CDK5, indicating a therapeutic potential. Molecular docking was carried out to understand the binding mode and interaction of the compounds with the target enzymes. Key interactions observed, such as H-bonds, promoted the binding, and weaker ones, such as van der Waals attractions, reinforced it. These findings suggest that these two Tamarix species possess bioactive properties with health-promoting effects.
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Hydrophilic, lipophilic extracts and essential oil of four hops varieties from Slovenia were examined in this study. Lipophilic extracts were obtained by supercritical extraction (SFE), while for hydrophilic extracts ultrasound and microwave extraction were employed. Essential oils were isolated by the hydrodistillation process. The lipophilic composition of essential oils and lipophilic extracts was determined by GC-MS analysis. Monoterpenes and sesquiterpene hydrocarbons were the most abundant class of compounds in oils (62.27-79.65 %), with myrcene being the most abundant constituent. Limonene and trans-caryophyllene were two terpenes determined in all essential oils while only trans-caryophyllene was detected in SFE samples. Antioxidant, antimicrobial, and cytotoxic activity, determined by applying in vitro assays, was more influenced by extraction technique than by varieties. Molecular docking was carried out to gain insight into the potential cancer protein targets BCL-2 and MMP9, whereby humulene epoxide II displayed good binding configuration within the cavities of the two proteins.
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Humulus , Aceites Volátiles , Sesquiterpenos Policíclicos , Humulus/química , Simulación del Acoplamiento Molecular , Aceites Volátiles/química , Terpenos/químicaRESUMEN
Plant species C. majus, which is a very rich source of secondary metabolites, was used to obtain extracts, using a conventional extraction technique. For the extraction of bioactive molecules, three solvents were used: ethyl acetate, methanol and water, which differ from each other based on their polarity. The obtained extracts were examined in terms of chemical composition, antioxidant, enzyme inhibitory activity, and cytotoxic effects. The research results indicate that methanol was a better and more efficient extractant in the process of isolating bioactive compounds than ethyl acetate and water. The chemical composition of this solvent, i.e. its polarity, contributed the most to the extraction of alkaloids and flavonoids. The high content of total phenolic compounds in the methanol extract, as well as individual alkaloids, caused a very strong antioxidant activity, as well as a strong inhibitory power when it comes to inhibiting the excessive activity of cholinesterase and tyrosinase. Methanol and ethyl acetate extracts achieved very good cytotoxic activity against cancerous cells HGC-27 and HT-29 and did not exert a toxic effect on non-cancerous cell lines (HEK293). Extracts of plant species C. majus, especially methanol extract could be characterized as a very good starting plant material for the formulation of products intended for various branches of the food and pharmaceutical industry.
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Acetatos , Alcaloides , Chelidonium , Humanos , Extractos Vegetales/química , Chelidonium majus , Metanol , Células HEK293 , Estructura Molecular , Alcaloides/farmacología , Alcaloides/química , Solventes/química , Antioxidantes , Agua , Chelidonium/químicaRESUMEN
The present study was designed to evaluate the chemical composition, antioxidant, enzyme inhibition and cytotoxic properties of different extracts from aerial parts of V. diversifolium (family Scrophulariaceae), a plant that is native to Lebanon, Syria and Turkey. Six extracts, namely, hexane, dichloromethane (DCM), ethyl acetate (EtOAc), ethanol (EtOH), 70% EtOH, and water (aqueous) were prepared by maceration. The EtOH extract was predominated by the presence of rutin (4280.20 µg g-1) and p-coumaric acid (3044.01 µg g-1) while the highest accumulation of kaempferol-3-glucoside (1537.38 µg g-1), caffeic acid (130.13 µg g-1) and 4-hydroxy benzoic acid (465.93 µg g-1) was recorded in the 70% EtOH, aqueous, and EtOAc extracts, respectively. The EtOH (46.86 mg TE/g) and 70% EtOH (46.33 mg TE/g) extracts displayed the highest DPPH radical scavenging result. Both these extracts, along with the aqueous one, exerted the highest ABTS radical scavenging result (73.03-73.56 mg TE/g). The EtOH and 70% EtOH extracts revealed the most potent anti-AChE (2.66 and 2.64 mg GALAE/g) and anti-glucosidase (1.07 and 1.09 mmol ACAE/g) activities. The aqueous extract was the most efficacious in inhibiting the proliferation of prostate cancer (DU-145) cells with an IC50 of 8.71 µg/mL and a Selectivity Index of 3.7. In conclusion, this study appraised the use of V. diversifolium aerial parts as a potential therapeutic source for future development of phytopharmaceuticals that target specific oxidative stress-linked diseases including diabetes, cancer, cardiovascular disease, and Alzheimer's disease among others.
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Histone deacetylase 6 (HDAC6) contributes to cancer metastasis in several cancers, including triple-negative breast cancer (TNBC)-the most lethal form that lacks effective therapy. Although several efforts have been invested to develop selective HDAC6 inhibitors, none have been approved by the FDA. Toward this goal, existing computational studies used smaller compound libraries and shorter MD simulations. Here, we conducted a structure-based virtual screening of ZINC "Druglike" library containing 17,900,742 compounds using a Glide virtual screening protocol comprising various filters with increasing accuracy. The top 20 hits were subjected to molecular dynamics simulation, MM-GBSA binding energy calculations, and further ADMET prediction. Furthermore, enzyme inhibition assay and cell viability assay were performed on six available compounds from the identified hits. C4 (ZINC000077541942) with a good profile of predicted drug properties was found to inhibit HDAC6 (IC50: 4.7 ± 11.6 µM) with comparative affinity to that of the known HDAC6 selective inhibitor Tubacin (TA) in our experiments. C4 also demonstrated cytotoxic effects against triple-negative breast cancer (TNBC) cell line MDA-MB-231 with EC50 of 40.6 ± 12.7 µM comparable to that of TA (2-20 µM). Therefore, this compound, with pharmacophore features comprising a non-hydroxamic acid zinc-binding group, heteroaromatic linker, and cap group, is proposed as a novel HDAC6 inhibitor.
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Simulación de Dinámica Molecular , Neoplasias de la Mama Triple Negativas , Humanos , Supervivencia Celular , Histona Desacetilasa 6/antagonistas & inhibidores , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/química , Simulación del Acoplamiento Molecular , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , ZincRESUMEN
Phytolacca americana L. is of great interest as a traditional additive in various folk remedies in several countries, including Turkey. We aimed to determine the chemical profile (assisted by high-Performance liquid chromatography-electrospray ionization-tandem mass apectrometry (HPLC-ESI-MS/MS) experiments of three extracts obtained by different polarity solvents viz. ethyl acetate (to extract semipolar compounds), methanol and water (to extract highly polar metabolites) from P. americana leaves. Their anti-diabetic effects were investigated in vitro by assessing their inhibition toα-amylase and α-glucosidase. Assessment of the neuroprotective potential of the three extracts was carried out against acetyl-(AChE) and butyryl-(BChE) cholinesterase enzymes. HPLC-ESI-MS/MS experiments showed a total of 17 chromatographic peaks primarily classified to six flavonoids, two saponins, and six fatty acids. Antioxidant assays revealed remarkable activity for the ethyl acetate and methanol extracts. The BChE inhibition was considerably more significant (4.08 mg galantamine equivalent (GALAE)/g) for the ethyl acetate extract, whereas the methanol extract had good inhibitory efficacy for AChE (2.05 mg GALAE/g). Through network pharmacology, the compounds' mechanism of action of targeted key gene in their associated diseases were identified. The hubb gene signal transducer and activator of transcription 3 (STAT3) and tumour necrosis factor (TNFα) where the P. americana compound's site of action in inflammation bowel disease. The results offer possibilities for the prospective application of P. americana in metabolic regulation, blood glucose control, and as a source of bioactive compounds with cholinesterase enzyme inhibitory characteristics which could be of relevance in the cosmetic or pharmaceutical industry for combating melanogenesis.Communicated by Ramaswamy H. Sarma.
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Hippomarathrum scabrum L. is an endemic medicinal plant in Turkey; however, there have been few studies investigating the phytochemistry and biological properties of these plants has not been investigated. The aim of this work is to determine the chemical composition of different extracts (extracts obtained by using supercritical carbon dioxide extraction, accelerated solvent extraction, homogenizer-assisted extraction, microwave-assisted extraction, and ultrasound-assisted extraction from Hippomarathrum scabrum L., and evaluate their biological properties. The analysis revealed that 5-O-caffeoylquinic acid, rutin, and isorhamnetin 3-O-rutinoside were the main bioactive compounds. The extract obtained by accelerated extraction contains the highest concentration of 5-O-Caffeoylquinic acid (7616.74 ± 63.09 mg/kg dry extract) followed by the extract obtained by homogenizer-assisted extraction (6682.53 ± 13.04 mg/kg dry extract). In antioxidant tests, all extracts expressed significant antioxidant activity. Also, cytotoxic and anticancer effects of these plant extracts were detected in the human prostate cancer cell line. Intrinsic apoptotic genes were up-regulated and anti-apoptotic genes were down-regulated in human prostate cancer cells after inhibition concentration dose treatment. The findings are promising, and suggest the use of these plant extracts could be used as natural sources with different biological activities, as well as anticancer agents.
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Antioxidantes , Ácido Clorogénico/análogos & derivados , Neoplasias de la Próstata , Ácido Quínico/análogos & derivados , Masculino , Humanos , Antioxidantes/análisis , Extractos Vegetales/química , Componentes Aéreos de las Plantas/químicaRESUMEN
The genus Stachys L., one of the largest genera of the Lamiaceae family, is highly represented in Turkey. This study was conducted to determine the bio-pharmaceutical potential and phenolic contents of six different extracts from aerial parts of Stachys tundjeliensis. The obtained results showed that the ethanol extract exhibited the highest antioxidant activity in the antioxidant assays. Meanwhile, the ethanol extract displayed strong inhibitory activity against α-tyrosinase, the dichloromethane extract exhibited potent inhibition against butyrylcholinesterase, and the n-hexane extract against α-amylase. Based on ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry analysis, more than 90 secondary metabolites, including hydroxybenzoic acid, hydroxycinnamic acid, and their glycosides, acylquinic acids, phenylethanoid glycosides, and various flavonoids were identified or tentatively annotated in the studied S. tundjeliensis extracts. It was observed that the application of S. tundjeliensis eliminated H2 O2 -induced oxidative stress. It was determined that protein levels of phospho-nuclear factor kappa B (NF-κB), receptor for advanced glycation endproducts, and activator protein-1, which are activated in the nucleus, decreased, and the synthesis of matrix metalloproteinase (MMP)-2 and MMP-9 also decreased to basal levels. Overall, these findings suggest that S. tundjeliensis contains diverse bioactive compounds for the development of nutraceuticals or functional foods with potent biological properties.
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Stachys , Stachys/química , Extractos Vegetales/química , Butirilcolinesterasa , Receptor para Productos Finales de Glicación Avanzada , Relación Estructura-Actividad , Antioxidantes/farmacología , Antioxidantes/química , Glicósidos , EtanolRESUMEN
Hibiscus sabdariffa L. (Family: Malvaceae) is believed to be domesticated by the people of western Sudan sometime before 4000 BC for their nutritional and medicinal properties. This study aimed to investigate the chemical profile, antioxidant activity, and enzyme inhibition property of extracts from red roselle (RR) and white roselle (WR) varieties grown in Sudan. Three aqueous extracts obtained by maceration, infusion, and decoction, in addition to the methanolic one, were prepared from the two roselle varieties. Results showed that the highest total phenolic and flavonoid contents of RR were obtained from the extracts prepared by infusion (28.40 mg GAE/g) and decoction (7.94 mg RE/g) respectively, while those from the WR were recorded from the methanolic extract (49.59 mg GAE/g and 5.81 mg RE/g respectively). Extracts of RR were mainly characterized by high accumulation of chlorogenic acid (6502.34-9634.96 mg kg-1), neochlorogenic acid (937.57-8949.61 mg kg-1), and gallic acid (190-4573.55 mg kg-1). On the other hand, neochlorogenic acid (1777.05-6946.39 mg kg-1) and rutin (439.29-2806.01 mg kg-1) were the dominant compounds in WR. All extracts from RR had significant (p < 0.05) higher antioxidant activity than their respective WR except in their metal chelating power, where the methanolic extract of the latter showed the highest activity (3.87 mg EDTAE/g). RR extracts prepared by infusion recorded the highest antioxidant values (35.09, 52.17, 65.62, and 44.92 mg TE/g) in the DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), CUPRAC (cupric ion reducing antioxidant capacity), and FRAP (ferric reducing antioxidant power) assays, respectively. All aqueous extracts from the WR exerted significant (p < 0.05) acetylcholinesterase (AChE) inhibitory activity (3.42-4.77 mg GALAE/g; GALAE = galantamine equivalents), while only one extract, obtained by maceration, from RR exerted AChE inhibitory activity (4.79 mg GALAE/g). All extracts of the RR showed relatively higher BChE (butyrylcholinesterase) inhibitory activity (3.71-4.23 mg GALAE/g) than the WR ones. Methanolic extracts of the two roselle varieties displayed the highest Tyr (tyrosinase) inhibitory activity (RR = 48.25 mg KAE/g; WR = 42.71 mg KAE/g). The methanolic extract of RR exhibited the highest amylase (0.59 mmol ACAE/g) and glucosidase (1.46 mmol ACAE/g) inhibitory activity. Molecular docking analysis showed that delphinidin 3,5-diglucoside, rutin, isoquercitrin, hyperoside, and chlorogenic acid exerted the most promising enzyme inhibitory effect. In conclusion, these findings indicated that the chemical profiles and biological activity of roselle varied according to the variety, extraction solvent, and technique used. These two roselle varieties can serve as a valuable source for the development of multiple formulations in food, pharmaceutical, and cosmetic industries.
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In this context, phytochemicals were extracted from Ranunculus constantinopolitanus using ethyl acetate (EA), ethanol, ethanol/water (70%), and water solvent. The analysis encompassed quantification of total phenolic and flavonoid content using spectrophotometric assays, chemical profiling via high performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) for the extracts, and assessment of antioxidant activity via 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), Cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), metal chelating (MCA), and phosphomolybdenum (PBD) assays. Moreover, antimicrobial activity was assessed against four different bacterial strains, as well as various yeasts. Enzyme inhibitory activities were evaluated against five types of enzymes. Additionally, the extracts were examined for their anticancer and protective effects on several cancer cell lines and the human normal cell line. All of the extracts exhibited significant levels of ferulic acid, kaempferol, and caffeic acid. All tested extracts demonstrated antimicrobial activity, with Escherichia coli and Pseudomonas aeruginosa being most sensitive to EA and ethanol extracts. Molecular docking studies revealed that kaempferol-3-O-glucoside strong interactions with AChE, BChE and tyrosinase. In addition, network pharmacology showed an association between gastric cancer and kaempferol-3-O-glucoside. Based on the results, R. constantinopolitanus can be a potential reservoir of bioactive compounds for future bioproduct innovation and pharmaceutical industries.
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Antiinfecciosos , Ranunculus , Humanos , Antioxidantes/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Espectrometría de Masas en Tándem , Simulación del Acoplamiento Molecular , Agua , Etanol , Antiinfecciosos/farmacología , Antiinfecciosos/análisisRESUMEN
The chemical composition as well as antioxidant, antiproliferative, and enzyme inhibition activities of extracts from aerial parts of Thymus leucostomus H ausskn. & V elen. obtained with hexane, methanol, and water were evaluated. Results showed that the methanol extract had significantly (p < 0.05) the highest total phenolic content (TPC; 107.80 mg GAE/g) and total flavonoids content (TFC; 25.21 mg RE/g) followed by the aqueous extract (102.72 mg GAE/g and 20.88 mg RE/g, respectively). LC-MS/MS-guided profiling of the three extracts revealed that rosmarinic acid (34.8%), hesperetin (42.9%), and linoleic acid (18%) were the dominant compounds in the methanol, aqueous and hexane extracts, respectively. GC-MS analysis of the hexane extract showed that É£-sitosterol (29.9%) was the major constituent. The methanol extract displayed significantly (p < 0.05) the highest Cu++ , Fe+++ , and Mo(VI) ions scavenging and reducing properties while the aqueous extract exerted significantly (p < 0.05) the highest metal chelating power (42.51 mg EDTAE/g). Both the hexane and methanol extracts effectively inhibited the acetylcholinesterase enzyme (2.63 and 2.65 mg GALAE/g, respectively) while the former extract exerted significantly (p < 0.05) the highest butyrylcholinesterase (2.32 mg GALAE/g), tyrosinase (19.73 mg KAE/g), and amylase (1.16 mmol ACAE/g) inhibition capacity. The aqueous extract exhibited the best glucosidase inhibition property (0.49 mmol ACAE/g). The methanol and hexane extracts exerted a higher cytotoxic effect on HT-29 (IC50 : 8.12 µg/mL) and HeLa (IC50 = 8.08 µg/mL) cells, respectively. In conclusion, these results provide valuable insight into the potential use of T. leucostomus bioactive extracts in different pharmaceutical applications.
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Antioxidantes , Hexanos , Antioxidantes/farmacología , Antioxidantes/química , Cromatografía Liquida , Cromatografía de Gases y Espectrometría de Masas , Hexanos/análisis , Metanol/análisis , Butirilcolinesterasa , Acetilcolinesterasa , Espectrometría de Masas en Tándem , Extractos Vegetales/química , Relación Estructura-ActividadRESUMEN
Plants from the Nepeta genus have been proved to possess different pharmacological properties, among which are antimicrobial, antioxidant, anti-inflammatory, analgesic, and cytotoxic effects. Nepeta italica is a medicinal plant traditionally used for its analgesic effects, and in the present study, the phytochemical composition and biological effects of hexane, dichloromethane (DCM), ethyl acetate (EA), ethanol, ethanol-water, and water extracts of the aerial parts were investigated for determining phenolic composition, antioxidant effects, and anti-inflammatory effects in isolated mouse colon specimens exposed to lipopolysaccharide (LPS). Polar extracts were the richest in terms of phenolic compounds, especially rosmarinic acid. In parallel, ethanol, ethanol-water, and water extracts were also the most effective as scavenging/reducing and enzyme inhibition agents, especially towards cholinesterases and α-glucosidase, and in inhibiting the LPS-induced cyclooxygenase-2 (COX-2) and tumor necrosis factor α (TNFα) gene expression in mouse colon. This poses the basis for future in vivo investigations for confirming the protective effects of polar extracts of N. italica against inflammatory bowel diseases.
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Bacteriophages (phages) are viruses that mainly infect bacteria and are ubiquitously distributed in nature, especially to their host. Phage engineering involves nucleic acids manipulation of phage genome for antimicrobial activity directed against pathogens through the applications of molecular biology techniques such as synthetic biology methods, homologous recombination, CRISPY-BRED and CRISPY-BRIP recombineering, rebooting phage-based engineering, and targeted nucleases including CRISPR/Cas9, zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). Management of bacteria is widely achieved using antibiotics whose mechanism of action has been shown to target both the genetic dogma and the metabolism of pathogens. However, the overuse of antibiotics has caused the emergence of multidrug-resistant (MDR) bacteria which account for nearly 5 million deaths as of 2019 thereby posing threats to the public health sector, particularly by 2050. Lytic phages have drawn attention as a strong alternative to antibiotics owing to the promising efficacy and safety of phage therapy in various models in vivo and human studies. Therefore, harnessing phage genome engineering methods, particularly CRISPR/Cas9 to overcome the limitations such as phage narrow host range, phage resistance or any potential eukaryotic immune response for phage-based enzymes/proteins therapy may designate phage therapy as a strong alternative to antibiotics for combatting bacterial antimicrobial resistance (AMR). Here, the current trends and progress in phage genome engineering techniques and phage therapy are reviewed.
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Infecciones Bacterianas , Bacteriófagos , Terapia de Fagos , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriófagos/genética , Farmacorresistencia Bacteriana/genética , BacteriasRESUMEN
Adenosine deaminase (ADA) is a Zn2+-containing enzyme that catalyzes the irreversible deamination of adenosine to inosine or deoxyadenosine to deoxyinosine. In addition to this enzymatic function, ADA mediates cell-to-cell interactions involved in lymphocyte co-stimulation or endothelial activation. ADA is implicated in cardiovascular pathologies such as atherosclerosis and certain types of cancers, including lymphoma and leukemia. To date, only two drugs (pentostatin and cladribine) have been approved for the treatment of hairy cell leukemia. In search of natural ADA inhibitors, we demonstrated the binding of selected phenolic compounds to the active site of ADA using molecular docking and molecular dynamics simulation. Our results show that phenolic compounds (chlorogenic acid, quercetin, and hyperoside) stabilized the ADA complex by forming persistent interactions with the catalytically essential Zn2+ ion. Furthermore, MM-GBSA ligand binding affinity calculations revealed that hyperoside had a comparable binding energy score (ΔG = - 46.56 ± 8.26 kcal/mol) to that of the cocrystal ligand in the ADA crystal structure (PDB ID: 1O5R) (ΔG = - 51.97 ± 4.70 kcal/mol). Similarly, chlorogenic acid exhibited a binding energy score (ΔG = - 18.76 ± 4.60 kcal/mol) comparable to those of the two approved ADA inhibitor drugs pentostatin (ΔG = - 14.54 ± 2.25 kcal/mol) and cladribine (ΔG = - 25.52 ± 4.10 kcal/mol) while quercetin was found to have modest binding affinity (ΔG = - 8.85 ± 7.32 kcal/mol). This study provides insights into the possible inhibitory potential of these phenolic compounds against ADA.
Asunto(s)
Inhibidores de la Adenosina Desaminasa , Pentostatina , Inhibidores de la Adenosina Desaminasa/farmacología , Inhibidores de la Adenosina Desaminasa/química , Simulación del Acoplamiento Molecular , Quercetina/farmacología , Cladribina , Ligandos , Ácido Clorogénico , Simulación de Dinámica MolecularRESUMEN
Faced with the serious consequences resulting from the abusive and repeated use of synthetic chemicals, today rethinking crop protection is more than necessary. It is in this context that the essential oils of the Lamiaceae Ocimum gratissimum and Ocimum canum, the Poaceae Cymbopogon citratus and nardus and a Rutaceae Citrus sp. of known chemical compositions were experimented. The evaluation of the larvicidal potential of the essential oils was done by the method of topical application of the test solutions, on the L1-L2 stage larvae from the first generation of S. frugiperda obtained after rearing in an air-conditioned room. Lethal concentrations (LC10 , LC50 and LC90 ) were determined after 48â h. After assessing the larvicidal potential of essential oils, molecular docking was carried out to study protein-ligand interactions and their propensity to bind to insect enzyme sites (AChE). The essential oil of O. gratissimum was the most effective with the lowest lethal concentrations (LC10 =0.91 %, LC50 =1.91 % and LC90 =3.92 %). The least toxic oil to larvae was Citrus sp. (LC10 =5.44 %, LC50 =20.50 % and LC90 =77.41 %). Molecular docking revealed that p-cymene and thymol from O. gratissimum essential oil are structurally similar and bind to the AChE active site via predominantly hydrophobic interactions and a H-bond with Tyr374 in the case of thymol. The essential oil of O. gratissimum constitutes a potential candidate for the development of biological insecticides for the fight against insect pests and for the protection of the environment.