scholarly journals Antitumor Activity and Mechanism of Robustic Acid from Dalbergia benthami Prain via Computational Target Fishing

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3919
Author(s):  
Juanjuan Huang ◽  
Ying Liang ◽  
Wenyu Tian ◽  
Jing Ma ◽  
Ling Huang ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Free Radical ◽  
Signaling Pathway ◽  
Inhibitory Activity ◽  
Topoisomerase I ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Radical Scavenging ◽  
Log P ◽  
Dependent Manner

Dalbergia benthami Prain (D.benthami) is an important legume species of the Dalbergia family, due to the use of its trunk and root heart in traditional Chinese medicine (TCM). In the present study, we reported the isolation, characterization and pharmacological activities of robustic acid (RA) from the ethyl acetate extract of D. benthami Prain. The SwissADME prediction showed that the RA satisfied the Lipinski’s rule of five (molecule weight (MW): 380.39 g/mol, lipid-water partition coefficient (log P): 3.72, hydrogen bond donors (Hdon): 1, hydrogen bond acceptors (Hacc): 6, rotatable bonds (Rbon): 3. Other chemical and pharmacological properties of this RA were also evaluated, including topological polar surface area (TPSA) = 78.13 Å and solubility (Log S) = −4.8. The probability values of the antineoplastic, anti-free radical activities and topoisomerase I (TopoI) inhibitory activity were found to be 0.784, 0.644 and 0.379, respectively. The molecular docking experiment using the Surflex-Dock showed that the Total Score and C Score of RNA binding with the human DNA-Topo I complex were 7.80 and 4. The MTS assay experiment showed that the inhibitory rates of RA on HL-60, MT4, Hela, HepG2, SK-OV-3 and MCF-7 cells were 37.37%, 97.41%, 81.22%, 34.4%, 32.68% and 51.4%, respectively. In addition, RA exhibited an inhibitory effect on the angiogenesis of zebrafish embryo, a good TopoI inhibitory activity at a 10 mM concentration and in a dose-dependent manner, excellent radical scavenging in the DPPH and ABTS assays, and the free radical scavenging rate was close to the positive control (BHT) at different concentrations (0.5–2.0 mg/mL). Furthermore, 18 potential targets were found for this RA by PharmMapper, including ANXA3, SRC, FGFR2, GSK3B, CSNK2B, YARS, LCK, EPHA2, MAPK14, RORA, CRABP2, PPP1CC, METAP2, MME, TTR, MET and KDR. The GO and KEGG pathway analysis revealed that the “protein tyrosine kinase activity”, “rap1 signaling pathway” and “PI3K-Akt signaling pathway” were significantly enriched by the RA target genes. Our results will provide new insights into the pharmaceutical use of this species. More importantly, our data will expand our understanding of the molecular mechanisms of RA functions.

Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells

2020 ◽  
Vol 20 (6) ◽  
pp. 734-750
Author(s):  
Wallax A.S. Ferreira ◽  
Rommel R. Burbano ◽  
Claudia do Ó. Pessoa ◽  
Maria L. Harada ◽  
Bárbara do Nascimento Borges ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Glioma Cell ◽  
Molecular Mechanisms ◽  
Glioma Cells ◽  
Dependent Manner ◽  
M Cell ◽  
Trypan Blue Exclusion ◽  
Cycle Arrest

Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). Results: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. Conclusions: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

scholarly journals Chemical Analysis, Toxicity Study, and Free-Radical Scavenging and Iron-Binding Assays Involving Coffee (Coffea arabica) Extracts

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4169
Author(s):  
Nuntouchaporn Hutachok ◽  
Pimpisid Koonyosying ◽  
Tanachai Pankasemsuk ◽  
Pongsak Angkasith ◽  
Chaiwat Chumpun ◽  
...  
Keyword(s):  
Free Radical ◽  
Mononuclear Cells ◽  
Radical Scavenging ◽  
Free Radical Scavenging ◽  
Chemical Compositions ◽  
Coffee Bean ◽  
Dependent Manner ◽  
Roasted Coffee ◽  
Instant Coffee ◽  
Radical Scavenging Properties

We aimed to analyze the chemical compositions in Arabica coffee bean extracts, assess the relevant antioxidant and iron-chelating activities in coffee extracts and instant coffee, and evaluate the toxicity in roasted coffee. Coffee beans were extracted using boiling, drip-filtered and espresso brewing methods. Certain phenolics were investigated including trigonelline, caffeic acid and their derivatives, gallic acid, epicatechin, chlorogenic acid (CGA) and their derivatives, p-coumaroylquinic acid, p-coumaroyl glucoside, the rutin and syringic acid that exist in green and roasted coffee extracts, along with dimethoxycinnamic acid, caffeoylarbutin and cymaroside that may be present in green coffee bean extracts. Different phytochemicals were also detected in all of the coffee extracts. Roasted coffee extracts and instant coffees exhibited free-radical scavenging properties in a dose-dependent manner, for which drip coffee was observed to be the most effective (p < 0.05). All coffee extracts, instant coffee varieties and CGA could effectively bind ferric ion in a concentration-dependent manner resulting in an iron-bound complex. Roasted coffee extracts were neither toxic to normal mononuclear cells nor breast cancer cells. The findings indicate that phenolics, particularly CGA, could effectively contribute to the iron-chelating and free-radical scavenging properties observed in coffee brews. Thus, coffee may possess high pharmacological value and could be utilized as a health beverage.

Strong antihemolytic and antioxidant properties of aqueous extract from Algerian Hammada elegans (Bge.) Botsch (Chenopodiaceae)

2021 ◽  
Vol 17 ◽  
Author(s):  
Brahim Asseli ◽  
Reguia Mahfoudi ◽  
Amar Djeridane ◽  
Mohamed Yousfi
Keyword(s):  
Free Radical ◽  
Aqueous Extract ◽  
Radical Scavenging Activity ◽  
Condensed Tannin ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Total Phenolic ◽  
Dependent Manner ◽  
Vitro Assay

Background: Research on medicinal plant antioxidants has emerged as a potential therapeutic to prevent free radical generated damage in the human body. Hammada elegans Botsch (popularly known as “Ajram”) is a xerophytic plant widely found in Laghouat region, but there are only a few reports about the biological or chemical properties of these species. Hence, the aim of this study is to investigate the antioxidant and the antihemolytic activities of hexanic, acetonic, methanolic and aqueous extracts of aerial parts of Algerian Hammada elegans Botsch by employing different in vitro assay systems. Methods: The total phenolic content, the flavonoid content and the condensed tannin amount were analyzed using Folin-Ciocalteu, aluminum chloride and vanillin assays, respectively. The in vitro antioxidant capacity of extracts was assessed by CUPRAC, iron chelating, ABTS•+and antihemolytic assays, and was expressed as EC50 values. Results: Among the analyzed extracts, the aqueous extract had the highest phenolic, flavonoid and tannin contents. Also, this extract displayed the highest antioxidant capacities compared to the other extracts and standards. Its EC50 value for ABTS radical-scavenging activity was 0.265 ± 0.003 mg/L. Moreover, this extract showed high iron (II) chelating ability (EC50 = 0.958 ± 0.001 mg/L), and good antioxidant activity in the cupric ion reducing activity (CUPRAC) in a concentration dependent manner (EC50 were 0.709 ± 0.002 mg/L). Additionally, this extract had the best antihemolytic activity against AAPH-induced hemolysis (EC50=0.090 ± 0.004 mg/L). Conclusion: Our study revealed that the aqueous extract of Hammada elegans Botsch, is a potential source of antioxidants which possess a high protective effect of membrane against free radical.

scholarly journals In vitro inhibitory potentials of ethanolic extract of Moringa oleifera flower against enzymes activities linked to diabetes

2021 ◽  
Vol 10 (4) ◽  
pp. 408-414
Author(s):  
Oluwaseun Ruth Olasehinde ◽  
Olakunle Bamikole Afolabi ◽  
Benjamin Olusola Omiyale ◽  
Oyindamola Adeniyi Olaoye
Keyword(s):  
Free Radical ◽  
Moringa Oleifera ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Ethanolic Extract ◽  
Antidiabetic Activity ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Antioxidant Power

Introduction: Diabetes mellitus (DM) has been recognized as the seventh leading cause of global mortality; however, researchers seek alternative means to manage the menace. The current study sought to investigate antioxidant potentials, α-amylase, and α-glucosidase inhibitory activities of ethanolic extract of Moringa oleifera flower in vitro. Methods: Antioxidant properties of the extract were appraised by assessing its inhibition against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH•), and hydrogen peroxide (H2O2) free radicals, as well as ferric reducing antioxidant power (FRAP), the antidiabetic activity was evaluated by α-amylase and α-glucosidase inhibition.Results: In this study, ethanolic extract of M. oleifera flower demonstrated a significant (P < 0.05) inhibition against DPPH free radical (43.57–83.56%) in a concentration-dependent manner, while FRAP (101.76 ± 1.63 mg/100 g), OH• scavenging ability (71.62 ± 0.95 mg/100 g), and H2O2 free radical scavenging capacity (15.33 ± 1.20 mg/100 g) were also observed. In the same manner, ethanolic extract of M. oleifera flower revealed a significant (P < 0.05) inhibition against α-amylase (IC50= 37.63 mg/mL) and α-glucosidase activities (IC50= 38.30 mg/mL) in the presence of their respective substrates in a concentration-dependent manner in comparison with acarbose. Conclusion: Ethanoic extract of M. oleifera flower could be useful as an alternative phytotherapy in the management of DM, having shown a strong antioxidative capacity and substantial inhibition against the activities of key enzymes involved in carbohydrate hydrolysis in vitro.

scholarly journals Radical scavenging activity of crude polysaccharides from Camellia sinensis

2011 ◽  
Vol 63 (3) ◽  
pp. 717-721
Author(s):  
Fan Yang ◽  
Zhiwei Yang ◽  
Jianbo Xiao
Keyword(s):  
Molecular Weight ◽  
Free Radical ◽  
Camellia Sinensis ◽  
Superoxide Radical ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Dependent Manner ◽  
Scavenging Activity ◽  
Concentration Dependent Manner ◽  
Molecular Weights

A preparation of crude polysaccharides (TPS) was isolated from Camellia sinensis by precipitation and ultrafiltration. TPS1, TPS2, and TPS3 had molecular weights of 240, 21.4, and 2.46 kDa, respectively. The radical scavenging activities of TPS were evaluated by DPPH free radical, hydroxyl radical and superoxide radical scavenging. These results revealed that TPS exhibited strong radical scavenging activity in a concentration-dependent manner. TPS3 with lowest molecular weight showed a higher radical scavenging activity.

scholarly journals Has Oxidative Stress any Role on Mechanisms of Aminophylline – Induced Seizures? An Animal Study

2015 ◽  
Vol 12 (4) ◽  
pp. 269-274 ◽  
Author(s):  
UK Roy ◽  
M Pal ◽  
S Datta ◽  
S Harlalka
Keyword(s):  
Oxidative Stress ◽  
Free Radicals ◽  
Free Radical ◽  
Molecular Mechanisms ◽  
Clinical History ◽  
Antioxidant Vitamin ◽  
Dependent Manner ◽  
Free Radical Generation ◽  
Radical Generation ◽  
Pre Treatment

Background Aminophylline can trigger seizures in patients without known underlying epilepsy or added risk factor for seizure exacerbation in epilepsy. Most of these seizures are difficult to control and are underappreciated compared to other drug toxicities. Despite a long clinical history of aminophylline-induced seizures, relatively little is known about the underlying molecular mechanisms that contribute to methylxanthine-induced seizure generation.Objective The present study evaluated the possible involvement of free radicals in aminophylline induced seizures in rat.Method The rats were divided into two groups. The first group graded single doses of aminophylline from 100 to 300 mg/kg were administered intraperitoneally. On the basis of the results Aminophylline, a dose (300 mg/kg) producing tonic-clonic seizures and mortality in 100% animals was selected as control in the study. The second group were subjected to single antioxidant (Vitamin E or Vitamin C) or in combination for 45 days then single doses of aminophylline 300 mg/kg administered intraperitoneally to rats.Result Aminophylline induced convulsions in rats in a dose-dependent manner, and both incidence of seizure and mortality were maximum at 300 mg/kg and there was significant increase of free radical generation. But though pre-treatment with antioxidants showed differential attenuating effects on aminophylline induced free radical generation as we all known but they were very much ineffective in antagonizing aminophylline induced seizures and post-seizure mortality by any appreciable extent.Conclusion Though Aminophylline induces oxidative stress the results are suggestive that at least free radicals is not only cause of convulsiogenic effects and post-seizure mortality of aminophylline.Kathmandu University Medical Journal Vol.12(4) 2014; 269-274

scholarly journals Evidence for the critical role of the PI3K signaling pathway in particulate matter-induced dysregulation of the inflammatory mediators COX-2/PGE2 and the associated epithelial barrier protein Filaggrin in the bronchial epithelium

2019 ◽  
Vol 36 (4) ◽  
pp. 301-313
Author(s):  
Chenjian Song ◽  
Lingjing Liu ◽  
Junjie Chen ◽  
Yiran Hu ◽  
Jingli Li ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Airway Inflammation ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Transmembrane Protein ◽  
Critical Role ◽  
Pi3k Signaling ◽  
Dependent Manner ◽  
Pi3k Signaling Pathway ◽  
Cox 2

AbstractParticulate matter (PM) is an environmental pollutant closely associated with human airway inflammation. However, the molecular mechanisms of PM-related airway inflammation remains to be fully elucidated. It is known that COX-2/PGE2 play key roles in the pathogenesis of airway inflammation. Filaggrin is a transmembrane protein contributing to tight junction barrier function. As such, Filaggrin prevents leakage of transported solutes and is therefore necessary for the maintenance of epithelial integrity. The objective of the present study was to investigate the regulatory mechanisms of COX-2/PGE2 and Filaggrin upon PM exposure both in vivo and in vitro. C57BL/6 mice received intratracheal instillation of PM for two consecutive days. In parallel, human bronchial epithelial cells (HBECs) were exposed to PM for 24 h. PM exposure resulted in airway inflammation together with upregulation of COX-2/PGE2 and downregulation of Filaggrin in mouse lungs. Corresponding dysregulation of COX-2/PGE2 and Filaggrin was also observed in HBECs subjected to PM. PM exposure led to the phosphorylation of ERK, JNK, and PI3K signaling pathways in a time-dependent manner, while blockade of PI3K with the specific molecular inhibitor LY294002 partially reversed the dysregulation of COX-2/PGE2 and Filaggrin. Moreover, pretreatment of HBECs with NS398, a specific molecular inhibitor of COX-2, and AH6809, a downstream PGE2 receptor inhibitor, reversed the downregulation of Filaggrin upon PM exposure. Taken together, these data demonstrated that the PI3K signaling pathway upregulated COX-2 as well as PGE2 and acted as a pivotal mediator in the downregulation of Filaggrin.

scholarly journals Pharmacological Evaluation of Selected Medicinal Plants Used in the Management of Oral and Skin Infections in Ebem-Ohafia District, Abia State, Nigeria

2018 ◽  
Vol 2018 ◽  
pp. 1-16
Author(s):  
Blessing O. Oyedemi ◽  
Sunday O. Oyedemi ◽  
Johnson V. Chibuzor ◽  
Ifeoma I. Ijeh ◽  
Roger M. Coopoosamy ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Medicinal Plants ◽  
Plant Extracts ◽  
Molecular Mechanisms ◽  
Current Trend ◽  
Radical Scavenging ◽  
Herbal Remedies ◽  
Dependent Manner ◽  
Skin Infections ◽  
Antioxidant Power

Oral and skin infections contribute significantly to the global health challenges responsible for the current trend of increased morbidity and premature death. The purpose of this study was to document medicinal plants used in the management of oral and skin infections in Ebem-Ohafia Local Government Area (LGA), Abia State, and to characterize the in vitro antioxidant and antibacterial activity. The thin layer chromatography (TLC) profiling of ten of the selected folklore medicine was carried out using a various solvent system of different polarity index. The antioxidant capacity of the plant extracts was evaluated using chemical-based methods, and its antibacterial effect was investigated using disc diffusion and microdilution methods. Sixty-one plant species belonging to 26 families were discovered, and the most frequently cited species are Euphorbiaceae (18.03%), Fabaceae (11.47%), and Asteraceae (11.47%). All the plant extracts showed a promising free radical scavenging activity and efficient ferric reducing antioxidant power in a concentration-dependent manner possibly due to their richness in polyphenol with TLC profiling showing maximum three bands of phytochemicals. Also, the plant extracts exhibited a mild to weak antibacterial activity against our panel of bacterial strains having MIC values ranging from 256 to > 512 μg/ mL reflected in their zone of inhibition at 10 μg/disc. The data obtained for Breynia nivosa (BN), Eleusine indica (EI), Cassia alata (CA), Chromolaena odorata (CO), and Acalypha hispida (AH) extracts substantiate the traditional use of these herbal remedies in the region and open the possibility for the development of cheaper and affordable drugs in the treatment of oral and skin infections. Further studies are needed to identify active ingredient with strong antibacterial and antioxidant capacities along with their molecular mechanisms.

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