RESUMO
The chemical profiles of both Zygophyllum album (Z. album) aerial parts and roots extracts were evaluated with LC-ESI-TOF-MS/MS analysis. Twenty-four compounds were detected. Among them, some are detected in both the aerial parts and the roots extracts, and others were detected in the aerial parts only. The detected compounds were mainly flavonoids, phenolic compounds, triterpenes and other miscellaneous compounds. Such compounds contribute to the diverse pharmacological activities elicited by the Z. album species. This study aimed to elucidate the antiepileptic effect of Z. album aerial parts and roots crude extracts against pentylenetetrazole (PTZ)-induced kindling in mice. Male albino mice were divided into four groups, eight animals each. All groups, except the control group, were kindled with PTZ (35 mg/kg i.p.), once every alternate day for a total of 15 injections. One group was left untreated (PTZ group). The remaining two groups were treated prior to PTZ injection with either Z. album aerial parts or roots crude extract (400 mg/kg, orally). Pretreatment with either extract significantly reduced the seizure scores, partially reversed the histological changes in the cerebral cortex and exerted antioxidant/anti-inflammatory efficacy evinced by elevated hippocampal total antioxidant capacity and SOD and catalase activities, parallel to the decrement in MDA content, iNOS activity and the TXNIB/NLRP3 axis with a subsequent decrease in caspase 1 activation and a release of IL-1ß and IL-18. Moreover, both Z. album extracts suppressed neuronal apoptosis via upregulating Bcl-2 expression and downregulating that of Bax, indicating their neuroprotective and antiepileptic potential. Importantly, the aerial parts extract elicited much more antiepileptic potential than the roots extract did.
RESUMO
The antimicrobial resistance of pathogenic microorganisms against commercial drugs has become a major problem worldwide. This study is the first of its kind to be carried out in Egypt to produce antimicrobial pharmaceuticals from isolated native taxa of the fungal Chaetomium, followed by a chemical investigation of the existing bioactive metabolites. Here, of the 155 clinical specimens in total, 100 pathogenic microbial isolates were found to be multi-drug resistant (MDR) bacteria. The Chaetomium isolates were recovered from different soil samples, and wild host plants collected from Egypt showed strong inhibitory activity against MDR isolates. Chaetomium isolates displayed broad-spectrum antimicrobial activity against C. albicans, Gram-positive, and Gram-negative bacteria, with inhibition zones of 11.3 to 25.6 mm, 10.4 to 26.0 mm, and 10.5 to 26.5 mm, respectively. As a consecutive result, the minimum inhibitory concentration (MIC) values of Chaetomium isolates ranged from 3.9 to 62.5 µg/mL. Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) analysis was performed for selected Chaetomium isolates with the most promising antimicrobial potential against MDR bacteria. The LC-MS/MS analysis of Chaetomium species isolated from cultivated soil at Assuit Governate, Upper Egypt (3), and the host plant Zygophyllum album grown in Wadi El-Arbaein, Saint Katherine, South Sinai (5), revealed the presence of alkaloids as the predominant bioactive metabolites. Most detected bioactive metabolites previously displayed antimicrobial activity, confirming the antibacterial potential of selected isolates. Therefore, the Chaetomium isolates recovered from harsh habitats in Egypt are rich sources of antimicrobial metabolites, which will be a possible solution to the multi-drug resistant bacteria tragedy.
Assuntos
Anti-Infecciosos , Chaetomium , Chaetomium/química , Cromatografia Líquida , Espectrometria de Massas em Tandem , Anti-Infecciosos/metabolismo , Antibacterianos/química , Bactérias/metabolismo , Testes de Sensibilidade Microbiana , SoloRESUMO
Crude or semi-purified extracts of plants can play a significant role as antitumor agents. They were used as stabilizing and reducing agents in the preparation of silver nanoparticles (AgNPs) that allows these particles to have more efficient cytotoxic activity. In the current study, the extract of Marrubium alysson L., a plant of common occurrence in Egypt was used to synthesize AgNPs for the first time, where comparison of anticancer activity of crude and phenolic extracts with the AgNPs were extensively studied against cancer cell lines PC-3 and HCT-116. Interestingly, AgNPs of the crude extract exhibited promising cytotoxicity with IC50 values of 10.4 and 16.3 µg/ml, while AgNPs of the phenolic extract exhibited very potent cytotoxicity with IC50 values of 2.66 and 1.34 µg/ml compared to Doxorubicin (as a standard reference drug) that exhibited IC50 values of 5.13 and 4.36 µg/ml, respectively against the tested cells. Additionally, AgNPs of the phenolic extract induced apoptosis in HCT-116 with a higher ratio than in PC-3 cells. It induced apoptosis in PC-3 cells by 79.3-fold change, while it induced total colon apoptotic cell death by 228.3-fold change compared to untreated control. Finally, the apoptotic activity of AgNPs of the phenolic extract in the treated PC-3 and HCT-116 cells was confirmed using RT-PCR. As a result, AgNPs of the phenolic extract could be considered a promising anticancer candidate through apoptosis-induction.Communicated by Ramaswamy H. Sarma.
RESUMO
Phytochemical study of the ethyl acetate root extract of Zygophyllum album has resulted in the isolation of a new saponin, Zygo-albuside D (1), along with two known compounds; (3-O-[ß-D-quinovopyranosyl]-quinovic acid) (2), which is first reported in the root, and catechin (3), first reported in the genus. Their chemical structures were established by NMR and high-resolution mass spectrometry (HRMS). The new saponin (1) exhibited promising cytotoxicity with IC50 values of 3.5 and 5.52 µM on A549 and PC-3 cancer cell lines, respectively, compared to doxorubicin with IC50 values of 9.44 and 11.39 µM on A549 and PC-3 cancer cell lines, respectively. While it had an IC50 value of 46.8 µM against WISH cells. Investigating apoptosis-induction, compound 1 induced total apoptotic cell death in A549 lung cancer cells by 32-fold; 21.53% compared to 0.67% in the untreated control cells. Finally, it upregulated the pro-apoptotic genes and downregulated the antiapoptotic gene using gene expression levels. Compound 1 exhibited remarkable CDK-2 target inhibition by 96.2% with an IC50 value of 117.6 nM compared to Roscovitine. The molecular docking study further confirmed the binding affinity of compound 1 as CDK2 and Bcl2 inhibitors that led to apoptosis induction in A549 cancer cells. Hence, this study highlights the importance of compound 1 in the design of a new anticancer agent with specific mechanisms.
RESUMO
This study uses a liquid chromatography-electrospray ionization-tandem mass spectrometry method to determine ß-Sitosterol and Ferulic acid in Pygeum africanum extract. Chromatographic separation of the two analytes was performed on an ACQUITY UPLC H-Class system coupled with Xevo TQD mass spectrometer and HSS T3 C18 column (2.1 X 50 mm, 1.8 µm). Mobile phase A consisted of an aqueous solution of 0.1% formic acid (v/v), and mobile phase B was 0.1% formic acid (v/v) in methanol pumped through a gradient elution mode. Mass spectrometer parameters were optimized using an electrospray ionization source in the positive and negative ionization modes. The quantification of the two analytes was performed using multiple reaction monitoring transitions. The method was fully validated per (FDA) guidelines regarding linearity, accuracy, precision, carryover and selectivity. The proposed method was applied successfully to determine the two investigated compounds in commercially available pharmaceutical products.
Assuntos
Prunus africana , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos TestesRESUMO
The main purpose of this work is to investigate the phytochemical composition of Marrubium alysson L. non-polar fraction. GC/MS analysis was used to evaluate the plant extract's saponifiable and unsaponifiable matter. Although M. alysson L. lipoidal matter saponification produced 30.3% of fatty acid methyl esters and 69.7% of unsaponifiable matter. Phytol was the most dominant substance in the unsaponifiable materials. Notably, marrubiin which is one of the most prominent metabolites of Marrubium alysson L. was not detected through our adopted GC/MS technique. Thus, further characterization was proceeded through simple and rapid HPTLC analysis which successfully managed to identify marrubiin. Based on the regression equation, the concentration of marrubiin in M. alysson L. extract was 14.09 mg/g of dry extract. Concerning acetylcholinesterase inhibitory activity, both the crude M. alysson L. total methanolic extract and the non-polar fraction displayed reasonable inhibitory activity against acetylcholinesterase (AChE), whereas the pure compound marrubiin was considered to be the most effective and potent AChE inhibitor, with an IC50 value of 52.66 (µM). According to the molecular docking studies, potential sites of interaction between the pure chemical marrubiin and AChE were examined. The results show that Tyr124 on AChE residue was critical to the activity of the aforementioned drug. Based on the depicted marrubin AChE inhibition activity and reported safety profile, this chemical metabolite is considered as a promising lead compound for further pre-clinical investigation as well as drug development and optimization.
RESUMO
The current work demonstrates a comparative study between aerial and root parts of Zygophyllum album L. The total phenolic (TPC) and flavonoid content (TFC), in addition to the antioxidant activity, of the crude extracts were investigated, where the aerial parts revealed a higher value overall. By means of UV-VIS and HPLC, rutin and caffeic acid were detected and then quantified as 5.91 and 0.97 mg/g of the plant extract, respectively. Moreover, the biosynthesis of AgNPs utilizing the crude extract of the arial parts and root of Z. album L. and the phenolic extracts was achieved in an attempt to enhance the cytotoxicity of the different plant extracts. The prepared AgNPs formulations were characterized by TEM and zeta potential measurements, which revealed that all of the formulated AgNPs were of a small particle diameter and were highly stable. The mean hydrodynamic particle size ranged from 67.11 to 80.04 nm, while the zeta potential ranged from 29.1 to 38.6 mV. Upon biosynthesis of the AgNPs using the extracts, the cytotoxicity of the tested samples was improved, so the polyphenolics AgNPs of the aerial parts exhibited a potent cytotoxicity against lung A549 and prostate PC-3 cancer cells with IC50 values of 6.1 and 4.36 µg/mL, respectively, compared with Doxorubicin (IC50 values of 6.19 and 5.13 µg/mL, respectively). Regarding the apoptotic activity, polyphenolics AgNPs of the aerial parts induced apoptotic cell death by 4.2-fold in PC-3 and 4.7-fold in A549 cells compared with the untreated control. The mechanism of apoptosis in both cancerous cells appeared to be via the upregulation proapoptotic genes; p53, Bax, caspase 3, 8, and 9, and the downregulation of antiapoptotic gene, Bcl-2. Hence, this formula may serve as a good source for anticancer agents against PC-3 and A549 cells.
RESUMO
Cynara scolymus L. (Family: Compositae) or artichoke is a nutritious edible plant widely used for its hepatoprotective effect. Crude extracts of flower, bract, and stem were prepared and evaluated for their in vitro antioxidant activity and phenolic content. The flower crude extract exhibited the highest phenolic content (74.29 mg GAE/gm) as well as the best in vitro antioxidant activity using total antioxidant capacity (TAC), ferric reducing antioxidant power (FEAP), and 1,1-diphenyl-2-picrylhyazyl (DPPH) scavenging assays compared with ascorbic acid. Phenolic fractions of the crude extracts of different parts were separated and identified using high-performance liquid chromatography HPLC-DAD analysis. The silver nanoparticles of these phenolic fractions were established and tested for their cytotoxicity and apoptotic activity. Results showed that silver nanoparticles of a polyphenolic fraction of flower extract (Nano-TP/Flowers) exhibited potent cytotoxicity against prostate (PC-3) and lung (A549) cancer cell lines with IC50 values of 0.85 µg/mL and 0.94 µg/mL, respectively, compared with doxorubicin as a standard. For apoptosis-induction, Nano-TP/Flowers exhibited apoptosis in PC-3 with a higher ratio than in A549 cells. It induced total prostate apoptotic cell death by 227-fold change while it induced apoptosis in A549 cells by 15.6-fold change. Nano-TP/Flowers upregulated both pro-apoptotic markers and downregulated the antiapoptotic genes using RT-PCR. Hence, this extract may serve as a promising source for anti-prostate cancer candidates.
Assuntos
Cynara scolymus , Nanopartículas Metálicas , Neoplasias , Antioxidantes/química , Apoptose , Ácido Ascórbico , Linhagem Celular , Cynara scolymus/química , Doxorrubicina , Inflorescência/química , Fenóis/química , Extratos Vegetais/química , Polifenóis/farmacologia , PrataRESUMO
Different parts of Cynara scolymus L. and their green synthesized eco-friendly silver nanoparticles (AgNPs) were screened for their cytotoxicity and apoptotic activity. Results showed that flower extract AgNPs exhibited more potent cytotoxicity compared to the normal form against PC-3 and A549 cell lines with IC50 values of 2.47 µg/mL and 1.35 µg/mL, respectively. The results were compared to doxorubicin (IC50 = 5.13 and 6.19 µg/mL, respectively). For apoptosis-induction, AgNPs prepared from the flower extract induced cell death by apoptosis by 41.34-fold change and induced necrotic cell death by 10.2-fold. Additionally, they induced total prostate apoptotic cell death by a 16.18-fold change, and it slightly induced necrotic cell death by 2.7-fold. Hence, green synthesized flower extract AgNPs exhibited cytotoxicity in A549 and PC-3 through apoptosis-induction in both cells. Consequently, synthesized AgNPs were further tested for apoptosis and increased gene and protein expression of pro-apoptotic markers while decreasing expression of anti-apoptotic genes. As a result, this formula may serve as a promising source for anti-cancer candidates. Finally, liquid chromatography combined with electrospray mass spectrometry (LC-ESI-MS) analysis was assessed to identify the common bioactive metabolites in crude extracts of stem, flower, and bract.
RESUMO
Phragmanthera austroarabica (Loranthaceae), a semi-parasitic plant, is well known for its high content of polyphenols that are responsible for its antioxidant and anti-inflammatory activities. Gallic acid, catechin, and methyl gallate are bioactive metabolites of common occurrence in the family of Loranthaceae. Herein, the concentrations of these bioactive metabolites were assessed using high-performance thin layer chromatography (HPTLC). Methyl gallate, catechin, and gallic acid were scanned at 280 nm. Their concentrations were assessed as 14.5, 6.5 and 43.6 mg/g of plant dry extract, respectively. Phragmanthera austroarabica extract as well as the three pure compounds were evaluated regarding the cytotoxic activity. The plant extract exhibited promising cytotoxic activity against MDA-MB-231 breast cells with the IC50 value of 19.8 µg/mL while the tested pure compounds displayed IC50 values in the range of 21.26-29.6 µg/mL. For apoptosis investigation, P. austroarabica induced apoptotic cell death by 111-fold change and necrosis by 9.31-fold change. It also activated the proapoptotic genes markers and inhibited the antiapoptotic gene, validating the apoptosis mechanism. Moreover, in vivo studies revealed a significant reduction in the breast tumor volume and weight in solid Ehrlich carcinoma (SEC) mice. The treatment of SEC mice with P. austroarabica extract improved both hematological and biochemical parameters with amelioration in the liver and kidney histopathology to near normal. Taken together, P. austroarabica extract exhibited promising anti-cancer activity through an apoptosis-induction.
RESUMO
Despite the efficient anti-cancer capabilities of methotrexate (MTX), it may induce myelosuppression, liver dysfunction and testicular toxicity. The purpose of this investigation was to determine whether Marrubium alysson L. (M. alysson L.) methanolic extract and its polyphenol fraction could protect mouse testicles from MTX-induced damage. We also investigated the protective effects of three selected pure flavonoid components of M. alysson L. extract. Mice were divided into seven groups (n = 8): (1) normal control, (2) MTX, (3) Methanolic extract + MTX, (4) Polyphenolic fraction + MTX, (5) Kaempferol + MTX, (6) Quercetin + MTX, and (7) Rutin + MTX. Pre-treatment of mice with the methanolic extract, the polyphenolic fraction of M. alysson L. and the selected pure compounds ameliorated the testicular histopathological damage and induced a significant increase in the serum testosterone level and testicular antioxidant enzymes along with a remarkable decline in the malondialdehyde (MDA) level versus MTX alone. Significant down-regulation of nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), p53 and miRNA-29a testicular expression was also observed in all the protected groups. Notably, the polyphenolic fraction of M. alysson L. displayed a more pronounced decline in the testicular levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and MDA, with higher testosterone levels relative to the methanolic extract. Further improvements in the Johnsen score, histopathological results and all biochemical assays were achieved by pre-treatment with the three selected pure compounds kaempferol, quercetin and rutin. In conclusion, M. alysson L. could protect against MTX-induced testicular injury by its antioxidant, anti-inflammatory, antiapoptotic activities and through the regulation of the miRNA-29a testicular expression. The present study also included chemical profiling of M. alysson L. extract, which was accomplished by LC-ESI-TOF-MS/MS analysis. Forty compounds were provisionally assigned, comprising twenty compounds discovered in the positive mode and seventeen detected in the negative mode.
RESUMO
Chemical investigation of the crude extract of the aerial part of Zygophyllum album L. (Z. album) led to the isolation of a new saponin, Zygo-albuside A (7), together with seven known compounds, one of them (caffeic acid, compound 4) is reported in the genus for the first time. NMR (1D and 2D) and mass spectrometric analysis, including high-resolution mass spectrometry (HRMS), were utilized to set up the chemical structures of these compounds. The present biological study aimed to investigate the protective antioxidant, anti-inflammatory, and antiapoptotic activities of the crude extract from the aerial part of Z. album and two of its isolated compounds, rutin and the new saponin zygo-albuside A, against methotrexate (MTX)-induced testicular injury, considering the role of miRNA-29a. In all groups except for the normal control group, which received a mixture of distilled water and DMSO (2:1) as vehicle orally every day for ten days, testicular damage was induced on the fifth day by intraperitoneal administration of MTX at a single dose of 20 mg/kg. Histopathological examination showed that pre-treatment with the crude extract of Z. album, zygo-albuside A, or rutin reversed the testicular damage induced by MTX. In addition, biochemical analysis in the protected groups showed a decrease in malondialdehyde (MDA), interleukin-6 (IL-6) and IL-1ß, Bcl-2-associated-protein (Bax), and an increase in B-cell lymphoma 2 (Bcl-2) protein, catalase (CAT), superoxide dismutase (SOD) in the testis, along with an increase in serum testosterone levels compared with the unprotected (positive control) group. The mRNA expression levels of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), p53, and miRNA-29a were downregulated in the testicular tissues of the protected groups compared with the unprotected group. In conclusion, the study provides sufficient evidence that Z. album extract, and its isolated compounds, zygo-albuside A and rutin, could alleviate testicular damage caused by the chemotherapeutic agent MTX.
Assuntos
MicroRNAs , Saponinas , Zygophyllum , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Catalase/metabolismo , Dimetil Sulfóxido/farmacologia , Interleucina-6/metabolismo , Malondialdeído/metabolismo , Metotrexato/farmacologia , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Extratos Vegetais/química , RNA Mensageiro/metabolismo , Rutina/metabolismo , Rutina/farmacologia , Saponinas/metabolismo , Saponinas/farmacologia , Superóxido Dismutase/metabolismo , Testículo/metabolismo , Testosterona/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Água/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Cichorium endivia L. (Asteraceae) is a wide edible plant that grows in the Mediterranean region. In this study, a phytochemical investigation of C. endivia L. ethanolic extract led to the isolation of stigmasterol (1), ursolic acid (2), ß-amyrin (3), azelaic acid (4), vanillic acid (5), (6S, 7E)-6-hydroxy-4,7-megastigmadien-3,9-dione (S(+)-dehydrovomifoliol) (6), 4-hydroxy phenyl acetic acid (7), vomifoliol (8), ferulic acid (9), protocatechuic acid (10), kaempferol (11), p. coumaric acid (12), and luteolin (13). In addition, the total phenolic content as well as the in vitro antioxidant activity of C. endivia L. extract were estimated. Moreover, we inspected the potential gonado-protective effect of C. endivia crude extract, its phenolic fraction, and the isolated coumaric, vanillic, and ferulic acids against methotrexate (MTX)-induced testicular injury in mice. There were seven groups: normal control, MTX control, MTX + C. endivia crude extract, MTX + C. endivia phenolic fraction, MTX + isolated coumaric acid, MTX + isolated vanillic acid, and MTX + isolated ferulic acid. MTX was given by i.p. injection of a 20 mg/kg single dose. The crude extract and phenolic fraction were given with a dose of 100 mg/kg/day, whereas the compounds were given at a dose of 10 mg/kg/day. A histopathological examination was done. The testosterone level was detected in serum together with the testicular content of malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB), B-cell lymphoma 2 (Bcl-2), Bcl-2 associated x protein (Bax), p53, and miR-29a. C. endivia crude extract, the phenolic fraction, and the isolated compounds showed significant elevation in their levels of testosterone, CAT, SOD, Bcl-2 with a significant decrease in their levels of MDA, TNF-α, IL-1ß, IL-6, NF-κB, Bax, P53, and miR-29a compared to those of the MTX control group. In conclusion, C. endivia mitigated MTX-induced germ cell toxicity via anti-inflammatory, antioxidant, and antiapoptotic effects.
RESUMO
This study presents a comparison between two mistletoe plants-P. acacia and P. curviflorus-regarding their total phenolic contents and antioxidant and anticancer activities. P. curviflorus exhibited a higher total phenolics content (340.62 ± 19.46 mg GAE/g extract), and demonstrated higher DPPH free radical scavenging activity (IC50 = 48.28 ± 3.41µg/mL), stronger reducing power (1.43 ± 0.54 mMol Fe+2/g) for ferric ions, and a greater total antioxidant capacity (41.89 ± 3.15 mg GAE/g) compared to P. acacia. The cytotoxic effects of P. acacia and P. curviflorus methanol extracts were examined on lung (A549), prostate (PC-3), ovarian (A2780) and breast (MDA-MB-231) cancer cells. The highest anticancer potential for the two extracts was observed on PC-3 prostate cancer cells, where P. curviflorus exhibited more pronounced antiproliferative activity (IC50 = 25.83 µg/mL) than P. acacia (IC50 = 34.12 µg/mL). In addition, both of the tested extracts arrested the cell cycle at the Pre-G1 and G1 phases, and induced apoptosis. However, P. curviflorus extract possessed the highest apoptotic effect, mediated by the upregulation of p53, Bax, and caspase-3, 8 and 9, and the downregulation of Bcl-2 expression. In the pursuit to link the chemical diversity of P. curviflorus with the exhibited bioactivities, its metabolomic profiling was achieved by the LC-ESI-TOF-MS/MS technique. This permitted the tentative identification of several phenolics-chiefly flavonoid derivatives, beside some triterpenes and sterols-in the P. curviflorus extract. Furthermore, all of the metabolites in P. curviflorus and P. acacia were inspected for their binding modes towards both CDK-2 and EGFR proteins using molecular docking studies in an attempt to understand the superiority of P. curviflorus over P. acacia regarding their antiproliferative effect on PC-3 cancer cells. Docking studies supported our experimental results; with all of this taken together, P. curviflorus could be regarded as a potential prospect for the development of chemotherapeutics for prostate cancer.
RESUMO
Medicinal plants are widely used in folk medicine to treat various diseases. Thonningia sanguinea Vahl is widespread in African traditional medicine, and exhibits antioxidant, antibacterial, antiviral, and anticancer activities. T. sanguinea is a source of phytomedicinal agents that have previously been isolated and structurally elucidated. Herein, gas chromatography combined with tandem mass spectrometry (GC-MS/MS) was used to quantify epipinoresinol, ß-sitosterol, eriodictyol, betulinic acid, and secoisolariciresinol contents in the methanolic crude extract and its ethyl acetate fraction for the first time. The ethyl acetate fraction was rich in epipinoresinol, eriodictyol, and secoisolariciresinol at concentrations of 2.3, 3.9, and 2.4 mg/g of dry extract, respectively. The binding interactions of these compounds with the epidermal growth factor receptor (EGFR) were computed using a molecular docking study. The results revealed that the highest binding affinities for the EGFR signaling pathway were attributed to eriodictyol and secoisolariciresinol, with good binding energies of -19.93 and -16.63 Kcal/mol, respectively. These compounds formed good interactions with the key amino acid Met 769 as the co-crystallized ligand. So, the ethyl acetate fraction of T. sanguinea is a promising adjuvant therapy in cancer treatments.
Assuntos
Balanophoraceae , Espectrometria de Massas em Tandem , Acetatos , Butileno Glicóis , Receptores ErbB , Flavanonas , Cromatografia Gasosa-Espectrometria de Massas , Lignanas , Simulação de Acoplamento Molecular , Triterpenos Pentacíclicos , Extratos Vegetais/química , Sitosteroides , Ácido BetulínicoRESUMO
Introduction: Diabetes mellitus is a chronic metabolic disorder that exhibited great expansion all over the world. It is becoming an epidemic disease adding a major burden to the health care system, particularly in developing countries. Methods: The plant under investigation in the current study Phragmanthera austroarabica A. G. Mill and J. A. Nyberg is traditionally used in Saudi Arabia for the treatment of diabetes mellitus. The methanolic extract (200 mg/kg) of the plant and pure gallic acid (40 mg/kg), a major metabolite of the plant, as well as their silver nanoparticle formulae (AgNPs) were evaluated for their antidiabetic activity. Results and Discussion: The results showed a decrease in body fat, obesity, an improvement in lipid profiles, normalization of hyperglycemia, insulin resistance, and hyperinsulinemia, and an improvement in liver tissue structure and function. However, the results obtained from AgNPs for both extract and the pure gallic acid were better in most measured parameters. Additionally, the activity of both the crude extract of the plant and its AgNPs were evaluated against a number of gram-positive, gram-negative bacteria and fungi. Although the activity of the crude extract ranged from moderate to weak or even non-active, the AgNPs of the plant extract clearly enhanced the antimicrobial activity. AgNPs of the extract demonstrated remarkable activity, especially against the Gram-negative pathogens Proteus vulgaris (MIC 2.5 µg/ml) and Pseudomonas aeruginosa (MIC 5 µg/ml). Furthermore, a promising antimicrobial activity was shown against the Gram-positive pathogen Streptococcus mutants (MIC 1.25 µg/ml).
RESUMO
The chemical constituents of the nonpolar fractions of the bamboo shoot skin Phyllostachys heterocycla were extensively studied. The phytochemical study was divided into two parts: the first deals with isolation of the chemical constituents using different chromatographic techniques that resulted in isolation of four compounds. The chemical structures of the pure isolated compounds were elucidated using different spectroscopic data. The second part deals with identification of the rest of the constituents using the GC technique. Additionally, both crude extract and the pure isolated compounds were investigated for cytotoxic activity. One of the isolated compounds; namely glyceryl 1-monopalmitate showed highly promising effect against the MCF-7 cells with (IC50 = 19.78 µM) compared to 5-FU (26.98 µM), and it remarkably stimulated apoptotic breast cancer cell death with 31.6-fold (16.13% compared to 0.51 for the control) at pre-G1 and G2/M-phase cell cycle arrest and blocked the progression of MCF-7 cells. Moreover, the identified compounds especially 1 were found to have high binding affinity towards both TPK and VEGFR-2 through the molecular docking studies which highlight its mode of action. HighlightsChemical profiling of Phyllostachys heterocycla bark nonpolar extract was fully identified.Glyceryl 1-monopalmitate showed highly promising effect against the MCF-7 cells with (IC50 = 19.78 µM) compared to 5-FU (26.98 µM).Glyceryl 1-monopalmitate significantly stimulated apoptotic breast cancer cell death with 31.6-fold by arresting cell cycle at G2/M and preG1 phases.Molecular docking simulation showed good binding affinities towards TPK and VEGFR-2 proteins.Communicated by Ramaswamy H. Sarma.
Assuntos
Antineoplásicos , Neoplasias da Mama , Extratos Vegetais , Feminino , Humanos , Antineoplásicos/química , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Fluoruracila , Células MCF-7 , Simulação de Acoplamento Molecular , Estrutura Molecular , Casca de Planta/química , Relação Estrutura-Atividade , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Extratos Vegetais/farmacologia , Poaceae/químicaRESUMO
Plicosepalus acacia (Fam. Loranthaceae) has been reported to possess hypoglycemic, antioxidant, antimicrobial, and anti-inflammatory effects. Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) analysis revealed the presence of a high content of polyphenolic compounds that are attributed to the therapeutic effects of the crude extract. In addition, methyl gallate and quercetin were detected as major phytomedicinal agents at concentrations of 1.7% and 0.062 g%, respectively, using high-performance thin layer chromatography (HPTLC). The present study investigated the effect of the P. acacia extract and its isolated compounds, methyl gallate and quercetin, on hind limb ischemia induced in type 1 diabetic rats. Histopathological examination revealed that treatment with P. acacia extract, methyl gallate, and quercetin decreased degenerative changes and inflammation in the ischemic muscle. Further biochemical assessment of the hind limb tissue showed decreased oxidative stress, increased levels of nitric oxide and endothelial nitric oxide synthase (eNOS), and enhancement of the levels of heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) in the groups treated with methyl gallate and quercetin. Expression levels of hypoxia inducible factor-1 alpha (HIF-1α), VEGF, fibroblast growth factor-2 (FGF-2), and miR-146a were upregulated in the muscle tissue of methyl gallate- and quercetin-treated groups along with downregulation of nuclear factor kappa B (NF-κB). In conclusion, P. acacia extract and its isolated compounds, methyl gallate and quercetin, mediated therapeutic angiogenesis in diabetic hind limb ischemia.
RESUMO
The current study was designed to investigate the antioxidant and cytotoxic activities of Thonningia sanguinea whole-plant extract. The total phenolic content was determined using Folin-Ciocalteu reagent and found to be 980.1 mg/g, calculated as gallic acid equivalents. The antioxidant capacity was estimated for the crude extract and the phenolic portion of T. sanguinea, whereupon both revealed a dose-dependent scavenging rate of DPPH⢠with EC50 values of 36.33 and 11.14 µg/mL, respectively. Chemical profiling of the plant extract was achieved by LC-ESI-TOF-MS/MS analysis, where 17 compounds were assigned, including ten compounds detected in the negative mode and seven detected in the positive mode. The phenolic portion exhibited promising cytotoxic activity against MCF-7 and HepG2 cells, with IC50 values of 16.67 and 13.51 µg/mL, respectively. Phenolic extract treatment caused apoptosis in MCF-7 cells, with total apoptotic cell death 18.45-fold higher compared to untreated controls, arresting the cell cycle at G2/M by increasing the G2 population by 39.7%, compared to 19.35% for the control. The apoptotic investigation was further validated by the upregulation of proapoptotic genes of P53, Bax, and caspases-3,8 9, and the downregulation of Bcl-2 as the anti-apoptotic gene. Bcl-2 inhibition was also virtualized by good binding interactions through a molecular docking study. Taken together, phenolic extract exhibited promising cytotoxic activity in MCF-7 cells through apoptosis induction and antioxidant activation, so further fractionation studies are recommended for the phenolic extract for specifying the most active compound to be developed as a novel anti-cancer agent.
RESUMO
Cisplatin is a powerful anti-neoplastic drug that displays multi-organ toxicity, especially to the liver and kidneys. Consumption of phytomedicines is a promising strategy to overcome the side effects of chemotherapy. Carrichtera annua extract proved to possess potent antioxidant activity. Its protective potential against cisplatin-induced hepato-nephrotoxicity was scrutinized. Moreover, a phytochemical study was conducted on C. annua ethyl acetate fraction which led to the isolation of five known phenolic compounds. Structure determination was achieved utilizing 1H- and 13C-NMR spectral analyses. The isolated phytochemicals were trans-ferulic acid (1), kaempferol (2), p-coumaric acid (3), luteolin (4) and quercetin (5). Regarding our biological study, C. annua has improved liver and kidney deteriorated functions caused by cisplatin administration and attenuated the histopathological injury in their tissues. Serum levels of ALT, AST, blood urea nitrogen and creatinine were significantly decreased. C. annua has modulated the oxidative stress mediated by cisplatin as it lowered MDA levels while enhanced reduced-GSH concentrations. More importantly, the plant has alleviated cisplatin triggered inflammation, apoptosis via reduction of INFγ, IL-1ß and caspase-3 production. Moreover, mitochondrial injury has been ameliorated as remarkable increase of mtDNA was noted. Furthermore, the MTT assay proved the combination of cisplatin-C. annua extract led to growth inhibition of MCF-7 cells in a notable additive way. Additionally, we have investigated the binding affinity of C. annua constituents with caspase-3 and IFN-γ proteins using molecular simulation. All the isolated compounds exhibited good binding affinities toward the target proteins where quercetin possessed the most auspicious caspase-3 and IFN-γ inhibition activities. Our results put forward that C. annua is a promising candidate to counteract chemotherapy side effects and the observed activity could be attributed to the synergism between its phytochemicals.