Albumin-coated green-synthesized zinc oxide nanoflowers inhibit skin melanoma cells growth via intra-cellular oxidative stress.

Zinc oxide (ZnO) has attracted a substantial interest in cancer research owing to their promising utility in cancer imaging and therapy. This study aimed to synthesized ZnO nanoflowers coated with albumin to actively target and the inhibit skin melanoma cells. We synthesized bovine serum albumin (BSA)-coated ZnO nanoflowers (BSA@ZnO NFs) and evaluated it's in vitro and in vivo therapeutic efficacy for skin cancer cells. BSA@ZnO NFs were prepared via single-step reduction method in the presence of plant extract (Heliotropium indicum) act as a capping agent, and further the successful fabrication was established by various physico-chemical characterizations, such as scanning electron microscopy (SEM), Fourier transform infra-red (FT-IR) spectroscopy, and x-rays diffraction (XRD) analysis. The fabricated BSA@ZnO NFs appeared flower like with multiple cone-shaped wings and average hydration size of 220.8 ± 12.6 nm. Further, BSA@ZnO NFs showed enhanced cellular uptake and cytocidal effects against skin cancer cells by inhibiting their growth via oxidative stress compared uncoated ZnO NFs. Moreover, BSA@ZnO NFs showed enhance biosafety, blood circulation time, tumor accumulation and in vivo tumor growth inhibition compared to ZnO NFs. In short, our findings suggesting BSA@ZnO NFs as a promising candidate for various types of cancer treatment along with chemotherapy.

From nature to nanotechnology: The interplay of traditional medicine, green chemistry, and biogenic metallic phytonanoparticles in modern healthcare innovation and sustainability.

As we navigate the modern era, the intersection of time-honoured natural remedies and contemporary scientific approaches forms a burgeoning frontier in global healthcare. For generations, natural products have been foundational to health solutions, serving as the primary healthcare choice for 80% to 85% of the world's population. These herbal-based, nature-derived substances, significant across diverse geographies, necessitate a renewed emphasis on enhancing their quality, efficacy, and safety. In the current century, the advent of biogenic phytonanoparticles has emerged as an innovative therapeutic conduit, perfectly aligning with principles of environmental safety and scientific ingenuity. Utilizing green chemistry techniques, a spectrum of metallic nanoparticles including elements such as copper, silver, iron, zinc, and titanium oxide can be produced with attributes of non-toxicity, sustainability, and economic efficiency. Sophisticated herb-mediated processes yield an array of plant-originated nanomaterials, each demonstrating unique physical, chemical, and biological characteristics. These attributes herald new therapeutic potentials, encompassing antioxidants, anti-aging applications, and more. Modern technology further accelerates the synthesis of natural products within laboratory settings, providing an efficient alternative to conventional isolation methods. The collaboration between traditional wisdom and advanced methodologies now signals a new epoch in healthcare. Here, the augmentation of traditional medicine is realized through rigorous scientific examination. By intertwining ethical considerations, cutting-edge technology, and natural philosophy, the realms of biogenic phytonanoparticles and traditional medicine forge promising pathways for research, development, and healing. The narrative of this seamless integration marks an exciting evolution in healthcare, where the fusion of sustainability and innovation crafts a future filled with endless possibilities for human well-being. The research in the development of metallic nanoparticles is crucial for unlocking their potential in revolutionizing fields such as medicine, catalysis, and electronics, promising groundbreaking applications with enhanced efficiency and tailored functionalities in future technologies. This exploration is essential for harnessing the unique properties of metallic nanoparticles to address pressing challenges and advance innovations across diverse scientific and industrial domains.

Cell cycle arrest and apoptotic studies of Terminalia chebula against MCF-7 breast cancer cell line: an in vitro and in silico approach.

Breast cancer is a leading cause of mortality in women, and alternative therapies with fewer side effects are actively being explored. Breast cancer is a significant global health concern, and conventional treatments like radiotherapy and chemotherapy often have side effects. Medicinal plant extracts offer a promising avenue for the development of effective and safe anticancer therapies. Terminalia chebula, a plant known for its medicinal properties, was selected for investigation in this study. We aimed to assess the antiproliferative effects of TCF extract on breast cancer cells and explore the potential role of saccharopine, a phytochemical found in TCF, as an anticancer agent. MCF7 breast cancer cell lines were exposed to TCF extract, and cell viability and apoptosis assays were performed to evaluate the antiproliferative and apoptogenic effects. Molecular docking studies were conducted to assess the binding affinity of saccharopine with EGFRs. Molecular dynamics simulations and binding energy calculations were employed to analyze the stability of the EGFR-saccharopine complex. The TCF extract exhibited significant antiproliferative effects on MCF7 breast cancer cells and induced apoptosis in a dose-dependent manner. Molecular docking analysis revealed that saccharopine demonstrated a higher binding affinity with EGFR compared to the reference compound (17b-estradiol). The subsequent MDS simulations indicated stable binding patterns and conformation of the EGFR-saccharopine complex, suggesting a potential role in inhibiting EGFR-mediated signaling pathways. The investigation of Terminalia chebula fruit extract and its phytochemical saccharopine has revealed promising antiproliferative effects and a strong binding affinity with EGFR. These findings provide a foundation for future research aimed at isolating saccharopine and conducting in vivo studies to evaluate its potential as a targeted therapy for breast cancer. The development of novel anticancer agents from plant sources holds great promise in advancing the field of oncology and improving treatment outcomes for breast cancer patients.

Innovative production of value-added products using agro-industrial wastes via solid-state fermentation.

The prevalence of organic solid waste worldwide has turned into a problem that requires comprehensive treatment on all fronts. The amount of agricultural waste generated by agro-based industries has more than triplet. It not only pollutes the environment but also wastes a lot of beneficial biomass resources. These wastes may be utilized as a different option/source for the manufacturing of many goods, including biogas, biofertilizers, biofuel, mushrooms and tempeh as the primary ingredients in numerous industries. Utilizing agro-industrial wastes as good raw materials may provide cost reduction and lower environmental pollution levels. Agro-industrial wastes are converted into biofuels, enzymes, vitamin supplements, antioxidants, livestock feed, antibiotics, biofertilizers and other compounds via solid-state fermentation (SSF). By definition, SSF is a method used when there is little to no free water available. As a result, it permits the use of solid materials as biotransformation substrates. Through SSF methods, a variety of microorganisms are employed to produce these worthwhile things. SSFs are therefore reviewed and discussed along with their impact on the production of value-added items. This review will provide thorough essential details information on recycling and the use of agricultural waste.

Assessment of antimicrobial and anthelmintic activity of silver nanoparticles bio-synthesized from Viscum orientale leaf extract.

BACKGROUND: Viscum orientale is a largely used parasitic plant with traditional medicinal properties. They are considered to possess the medicinal properties of host tree which they grow on. It's a least explored plant with ethanopharmacological importance. As a result, the current work aimed to investigate the biological effects of Viscum orientale extract and silver nanoparticles (AgNPs) generated from it. METHODS: AgNPs synthesized using Viscum orientale plant extract and analysed on time dependent series and was characterized using Ultra Violet UV-visible spectra, Fourier Transform Infrared Spectroscopy FTIR, X-ray diffraction (XRD), Energy Dispersive X-ray Spectroscopy (EDX), Scanning Electron Microscopy (SEM). Further using disc method anti-microbial assay was performed following antioxidation screening using 1,1-diphenyl-2-picryl-hydrazyl (DPPH), reducing power and nitric oxide content and heamgglutination with human blood. RESULTS: On green synthesis using silver, the phyto contituents of plant Viscum orientale effectively reduced silver ions at 3-4 h of continuous stirring to form AgNPs. UV-vis spectra showed a typical peak of AgNPs at 480 nm. The FTIR analysis confirmed the covering of silver layers to bio-compounds of the extract. SEM analysis represented AgNPs as spherical morphologies ranging from 119-222 nm. AgNPs exhibited impressive zone of inhibition against Escherichia coli (8.1 ± 0.3 mm), Staphylococcus aureus (10.3 ± 0.3 mm), Bacillus subtilis (7.3 ± 0.3 mm), Bacillus cereus (8.2 ± 0.3 mm), Salmonella typhi (7.1 ± 0.2 mm). AgNps exhibited efficiency against DPPH at EC50 value of 57.60 µg/ml. and reducing power at EC50 of 53.42 µg/ml and nitric oxide scavenging of EC50 of 56.01 µg/ml concentration. Further, anthelmintic activity results showed synthesized nanoparticles significant reduction in the paralysis time to 5.4 ± 0.3 min and death time to 6.5 ± 0.6 min in contrast to the individual factors. On hemagglutination using AgNPs, above 80 µg/ml of concentration showed very significant effect on comparison with water extract. CONCLUSION: Synthesized AgNPs using Viscum orientale water extract displayed versatile biological activity than individual extract. This study has forecasted a new path to explore more on this AgNPs for further research.

Network pharmacology and molecular docking study for biological pathway detection of cytotoxicity of the yellow jasmine flowers.

BACKGROUND: The yellow jasmine flower (Jasminum humile L.) is a fragrant plant belonging to the Oleaceae family with promising phytoconstituents and interesting medicinal uses. The purpose of this study was to characterize the plant metabolome to identify the potential bioactive agents with cytotoxic effects and the underlying mechanism of cytotoxic activity. METHODS: First, HPLC-PDA-MS/MS was used to identify the potential bioactive compounds in the flowers. Furthermore, we assessed the cytotoxic activity of the flower extract against breast cancer (MCF-7) cell line using MTT assay followed by the cell cycle, DNA-flow cytometry, and Annexin V-FITC analyses alongside the effect on reactive oxygen species (ROS). Finally, Network pharmacology followed by a molecular docking study was performed to predict the pathways involved in anti-breast cancer activity. RESULTS: HPLC-PDA-MS/MS tentatively identified 33 compounds, mainly secoiridoids. J. humile extract showed a cytotoxic effect on MCF-7 breast cancer cell line with IC50 value of 9.3 ± 1.2 µg/mL. Studying the apoptotic effect of J. humile extract revealed that it disrupts G2/M phase in the cell cycle, increases the percentage of early and late apoptosis in Annexin V-FTIC, and affects the oxidative stress markers (CAT, SOD, and GSH-R). Network analysis revealed that out of 33 compounds, 24 displayed interaction with 52 human target genes. Relationship between compounds, target genes, and pathways revealed that J. humile exerts its effect on breast cancer by altering, Estrogen signaling pathway, HER2, and EGFR overexpression. To further verify the results of network pharmacology, molecular docking was performed with the five key compounds and the topmost target, EGFR. The results of molecular docking were consistent with those of network pharmacology. CONCLUSION: Our findings suggest that J. humile suppresses breast cancer proliferation and induces cell cycle arrest and apoptosis partly by EGFR signaling pathway, highlighting J. humile as a potential therapeutic candidate against breast cancer.

Development of novel kinetic model based on microbiome and biochar for in-situ remediation of total petroleum hydrocarbons (TPHs) contaminated soil.

A novel kinetic model has been developed to explain the degradation of total petroleum hydrocarbons. Microbiome engineered biochar amendment may result in a synergistic impact on degradation of total petroleum hydrocarbons (TPHs). Therefore, the present study analyzed the potential of hydrocarbon-degrading bacteria A designated as Aeromonas hydrophila YL17 and B as Shewanella putrefaciens Pdp11 morphological characterized as rod shaped, anaerobic and gram-negative immobilized on biochar, and the degradation efficiency was measured by gravimetric analysis and gas chromatography-mass spectrometry (GC-MS). Whole genome sequencing of both strains revealed the existence of genes responsible for hydrocarbon degradation. In 60 days remediation setup, the treatment consisting of immobilization of both strains on biochar proved more efficient with less half-life and better biodegradation potentials compared to biochar without strains for decreasing the content of TPHs and n-alkanes (C12-C18). Enzymatic content and microbiological respiration showed that biochar acted as a soil fertilizer and carbon reservoir and enhanced microbial activities. The removal efficiency of hydrocarbons was found to be a maximum of 67% in soil samples treated with biochar immobilized with both strains (A + B), followed by biochar immobilized with strain B 34%, biochar immobilized with strain A 29% and with biochar 24%, respectively. A 39%, 36%, and 41% increase was observed in fluorescein diacetate (FDA) hydrolysis, polyphenol oxidase and dehydrogenase activities in immobilized biochar with both strains as compared to control and individual treatment of biochar and strains. An increase of 35% was observed in the respiration rate with the immobilization of both strains on biochar. While a maximum colony forming unit (CFU/g) was found 9.25 with immobilization of both strains on biochar at 40 days of remediation. The degradation efficiency was due to synergistic effect of both biochar and bacteria based amendment on the soil enzymatic activity and microbial respiration.

Environmentally benign silver bio-nanomaterials as potent antioxidant, antibacterial, and antidiabetic agents: Green synthesis using Salacia oblonga root extract.

Introduction: The use of plant extracts in the green synthesis of metallic nanoparticles is one of the simplest, most practical, economical, and ecologically friendly methods for avoiding the use of toxic chemicals. Method: Silver nanoparticles (AgNPs) were synthesized, employing a high-efficiency, non- toxic, cost-effective, green, and simple technique that included the use of Salacia oblonga root extract (SOR) as a capping agent compared to synthetic nanoparticles. The use of S. oblonga can be seen in traditional medicines for treating diabetes, obesity, rheumatism, gonorrhea, asthma, and hyperglycemia. The objectives of the current study were to green synthesize S. oblonga root extract silver nanoparticles (SOR-AgNPs), characterize them, and study their antioxidant, antibacterial, and antidiabetic activities. Result: The shape of SOR-AgNPs was spherical, at less than 99.8 nm in size, and exhibited a crystalline peak at XRD. The green synthesized SOR-AgNPs showed significant antioxidant properties like DPPH (80.64 µg/mL), reducing power capacity (81.09 ± SEM µg/mL), nitric oxide (96.58 µg/mL), and hydroxyl (58.38 µg/mL) radical scavenging activities. The MIC of SOR-AgNPs was lower in gram-positive bacteria. The SOR-AgNPs have displayed efficient inhibitory activity against α-amylase, with an EC50 of 58.38 µg/mL. Analysis of capping protein around the SOR-AgNPs showed a molecular weight of 30 kDa. Discussion: These SOR-AgNPs could be used as antibacterial and antidiabetic drugs in the future as it is cheap, non-toxic, and environmentally friendly. Bio-fabricated AgNPs had a significant impact on bacterial strains and could be used as a starting point for future antibacterial drug development.

Exploration of Anti-HIV Phytocompounds against SARS-CoV-2 Main Protease: Structure-Based Screening, Molecular Simulation, ADME Analysis and Conceptual DFT Studies.

The ever-expanding pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has gained attention as COVID-19 and caused an emergency in public health to an unmatched level to date. However, the treatments used are the only options; currently, no effective and licensed medications are available to combat disease transmission, necessitating further research. In the present study, an in silico-based virtual screening of anti-HIV bioactive compounds from medicinal plants was carried out through molecular docking against the main protease (Mpro) (PDB: 6LU7) of SARS-CoV-2, which is a key enzyme responsible for virus replication. A total of 16 anti-HIV compounds were found to have a binding affinity greater than -8.9 kcal/mol out of 150 compounds screened. Pseudohypericin had a high affinity with the energy of -10.2 kcal/mol, demonstrating amino acid residual interactions with LEU141, GLU166, ARG188, and GLN192, followed by Hypericin (-10.1 kcal/mol). Moreover, the ADME (Absorption, Distribution, Metabolism and Excretion) analysis of Pseudohypericin and Hypericin recorded a low bioavailability (BA) score of 0.17 and violated Lipinski's rule of drug-likeness. The docking and molecular simulations indicated that the quinone compound, Pseudohypericin, could be tested in vitro and in vivo as potent molecules against COVID-19 disease prior to clinical trials.This was also supported by the theoretical and computational studies conducted. The global and local descriptors, which are the underpinnings of Conceptual Density FunctionalTheory (CDFT) have beenpredicted through successful model chemistry, hoping that they could be of help in the comprehension of the chemical reactivity properties of the molecular systems considered in this study.

Effect of Vegetable Waste on Growth Performance and Hematology of Broiler Chicks.

Vegetable waste (spinach, potato, and cauliflower) is a rich and natural source of nutrients, potentially good for supplying minerals, essential amino acids, and antioxidants to the birds. Relatively, its cost very low, easily to accessible, easily process & pose little risk of illness. The aim of present study was to evaluate the effect of vegetable waste (VW) as feed supplement on growth performance and hematology of broiler chicks. For this purpose, a total of 200 (4 days old) vaccinated chicks were acquired from a commercial hatchery Multan which was acclimated for three weeks (21 days) on basal starter feed after that 25-day-old chicks with uniform body weight were allocated according to a CRD (completely randomized design) into four dietary treatments with three replicates of each contained 15 chicks in 12 pens. In dietary treatments, chicks were feed with basal feed (BF) and supplemented feed with vegetable waste (VW) of spinach, potato, and cauliflower. For this purpose, the dietary treatments included control treatment (T 1) (100% BF+0% VW) and other dietary treatments (T 2) (75% BF+25% VW), (T 3) (50% BF+50% VW), and (T 4) (25% BF+75% VW). The body weight, feed intake, food conversion ratio (FCR), and mortality were checked on weekly and daily basis. For hematology analysis, after the 1st experimental week (25-day-old chicks) and the last 5th experimental week (56-day-old chicks), the samples of blood were gathered from the wing's veins of two birds from each treatment in random way. At the end of five weeks (35 days), birds with uniform average body weight were selected per treatment with three replicates (2 bird/replicate) and then were manually slaughtered according to the Halal method to analyze the weight of internal body organs of broilers by physical and statistical analysis (ANOVA). There was no significant effect (P > 0.05) on feed intake and FCR among all the dietary treatments. But in average, body weight and BWG were higher in treatment (T 2) (P < 0.01) than all other dietary treatments (T 3) and (T 4) and control treatment (T 1). The blood constituents in this study showed that broilers in control treatment (T 1) and other dietary treatments (T 2), (T 3), and (T 4) fed on different doses were significantly (P < 0.01) different from each other. The week 5 (W 5) shows higher values of blood constituents (P < 0.01) than week 1 (W 1). The carcass yield of the chicks fed on different doses showed that they were significantly different (P < 0.01) among the dietary treatments. The VW inclusion 0%, 25%, 50%, and 75% had positive effect on blood constituents and carcass yield of the broiler chicks; they were significantly (P < 0.01) different among the treatments.

Optimization of Supercritical Carbon Dioxide Extraction of Saussurea costus Oil and Its Antimicrobial, Antioxidant, and Anticancer Activities.

Saussurea costus is a medicinal plant with different bioactive compounds that have an essential role in biomedicine applications, especially in Arab nations. However, traditional extraction methods for oils can lead to the loss of some volatile and non-volatile oils. Therefore, this study aimed to optimize the supercritical fluid extraction (SFE) of oils from S. costus at pressures (10, 20, and 48 MPa). The results were investigated by GC/MS analysis. MTT, DPPH, and agar diffusion methods assessed the extracted oils' anticancer, antioxidant, and antimicrobial action. GC/MS results showed that elevated pressure from 10 to 20 and 48 MPa led to the loss of some valuable compounds. In addition, the best IC50 values were recorded at 10 MPa on HCT, MCF-7, and HepG-2 cells at about 0.44, 0.46, and 0.74 µg/mL, respectively. In contrast, at 20 MPa, the IC50 values were about 2.33, 6.59, and 19.0 µg/mL, respectively, on HCT, MCF-7, and HepG-2 cells, followed by 48 MPa, about 36.02, 59.5, and 96.9 µg/mL. The oil extract at a pressure of 10 MPa contained much more of á-elemene, dihydro-à-ionone, patchoulene, á-maaliene, à-selinene, (-)-spathulenol, cedran-diol, 8S,13, elemol, eremanthin, á-guaiene, eudesmol, ç-gurjunenepoxide-(2), iso-velleral, and propanedioic acid and had a higher antioxidant activity (IC50 14.4 µg/mL) more than the oil extract at 20 and 48 MPa. In addition, the inhibitory activity of all extracts was higher than gentamicin against all tested bacteria. One of the more significant findings from this study is low pressure in SFE enhancement, the extraction of oils from S. costus, for the first time. As a result, the SFE is regarded as a good extraction technique since it is both quick and ecologically friendly. Furthermore, SFE at 10 MPa increased the production and quality of oils, with high antioxidant activity and a positive effect on cancer cells and pathogens.

Phenolic Characterization Using cLC-DAD Analysis and Evaluation of In Vitro and In Vivo Pharmacological Activities of Ruta tuberculata Forssk.

The perennial aromatic plant Ruta tuberculata Forssk (Rutaceae) has been traditionally used by Mediterranean peoples as folk medicine against several types of disease to treat diverse illness. The objective of this work is to evaluate the in vitro and in vivo pharmacological activities of the aqueous (RAE) and methanolic (MeOH) 80% (RME) extracts of Algerian R. tuberculata aerial parts. Antioxidant potential, neuro-protective and anti-arthritic activities were investigated in vitro using six antioxidant approaches and by determining acetyl-cholinesterase and bovine albumin denaturation inhibitory capacities, respectively. Furthermore, in vivo anti-ulcer and anti-inflammatory activities were evaluated on EtOH-induced gastric mucosal damage and carrageenan-induced paw edema models in mice. Moreover, bio-compounds' contents were also quantified using spectrophotometric and cLC-DAD methods. Both in vivo and in vitro investigations showed remarkable antioxidant activity of Ruta tuberculata Forssk, while methanolic extract (RME) of Ruta tuberculata Forssk exhibited more significant neuro-protective and anti-inflammatory effects. However, the antiulcer activity was more pronounced with RAE of R. tuberculata, which suggests that this plant can be considered as a natural resource of potent bioactive compounds that may act as antioxidant and anti-inflammatory agents, which underlines the importance of incorporating them in therapies in order to treat various diseases linked to oxidative stress, and they may also provide crucial data for the development of new anticholinesterase drugs to improve neurodegenerative diseases, such as Alzheimer's.

Molecular epidemiology of virulent E. coli among rural small scale dairy herds and shops: Efficacy of selected marine algal extracts and disinfectants.

Virulent pathotypes of E. coli seriously affect the livestock regarding the misuse of antibiotics. All 180 samples collected from cow's environment and dairy shops in Qena, Egypt were serologically and molecularly positive for coliforms. Enteropathogenic E. coli (EPEC), Shiga toxin-producing E. coli (STEC), Enteroinvasive E. coli (EIEC) and Enterotoxigenic E. coli (ETEC) pathotypes were isolated from water and milk-related samples. STEC serogroups O26, O55, O111, O113, O145 were also recovered. The non-O157 STEC serotypes were recovered from human diarrheagenic patients contacting cattle or consuming contaminated water/milk products. BlaCTX-M and blaTEM genes were detected in 25.5% and 100%, respectively. Disinfectants and algal extracts, identified by GC-MS, were evaluated in vitro for antibacterial activities. TH4+® disinfectant and methanol extract of Turbinaria decurrens reduced E. coli at 13 log10 at 1.5% and 3 mg/ml concentrations, respectively. Ag-NPs/T. decurrens showed 8-9 log10 reduction at concentration of 1.6 × 105 NPs/ml. Examined water sources, milk and milk products were potential reservoirs for virulent antibiotic-resistant E.coli which may impose animal and public health threats.Abbreviations: APEC: Avian pathogenic E. coli; blaCTX-M: ß-lactamase inhibitors-Cefotaximase gene; blaTEM: ß-lactamase inhibitors-Temoneira gene; CFU: Colony-forming unit; DAEC: Diffusely adherent E. coli; DEC: Diarrheagenic Escherichia coli; DEMSO: Dimethyl sulfoxide; eaeA: Intimin or E. coli attaching gene; EAEC: Enteroaggregative E. coli; EHEC: Enterohemorrhagic E. coli; EIEC: Enteroinvasive E. coli; EOSQC: Egyptian Organization for Standardization and Quality Control; EPEC: Enteropathogenic E. coli; ETEC: Enterotoxigenic E. coli; ExPEC: Extra-intestinal pathogenic E. coli; GC-MS: Gas chromatography-mass spectrometry technique; hly: Hemolysin gene; STEC: Shiga like producing E. coli; stx1: Shiga-toxin 1 gene; ESBLs: Extended-spectrum beta-lactamases.

Opposite Modulatory Effects of Crataegus aronia Aqueous Extract on Platelet Aggregation in Rats.

OBJECTIVES: To reveal the mechanisms behind the dual effects of Crataegus aronia (C. aronia) aqueous extract on platelet aggregation by focusing on function, regulation, expression, and signaling of platelets P2Y12 receptors. METHODS: Adult male Wistar rats (120 ± 10 g) were classified as control received the vehicle, C. aronia (200 mg/kg), and C. aronia (2,000 mg/kg)-treated rats. After treatments for consecutive 7 days, hematological and molecular experiments were conducted to detect alterations in platelet aggregation, thromboxane B2 (THXB2) and intracellular reactive oxygen species (ROS) content; protein levels of P2Y12, p-Akt, cyclic adenosine monophosphate (cAMP), phosphorylated vasodilator-stimulated-phosphoprotein (p-VASP), nuclear factor κB (NF-κB), P-selectin, and etc. in platelets were determined by Western blot; mRNA expressions of P2Y12 and some inflammatory markers were determined by real-time polymerase chain reaction. RESULTS: At a concentration of 200 mg/kg, C. aronia inhibited platelet aggregation through multiple interconnected mechanisms including downregulation P2Y12 synthesis and expression, stimulating intracellular cAMP levels and protein levels of p-VASP, inhibiting platelets THXB2 release and protein levels of P-selectin. Also, it inhibited platelets level of ROS and of NF-κB, a major signaling pathway that stimulates the expression of P2Y12 and THXA2 synthesis. Opposite findings were seen in platelets of rats received C. aronia at a concentration of 2,000 mg/kg. Interestingly, co-administration of N-acetylcysteine prevented all hematological and molecular alterations exerted by the high dose of the extract and inhibited platelet aggregation. CONCLUSION: Oral administration of C. aronia at low dose inhibits platelet aggregation by reducing THXB2 release, expression of P-selectin and activating cAMP and Akt signaling through two major mechanisms including downregulation of P2Y12 and inhibition of ROS-induced activation of NF-κB, an effect that is observed to be in the opposite direction with its high dose.

Phytochemical Screening and In-Vitro Antibacterial and Anticancer Activity of Crude Extract of Matricaria aurea.

BACKGROUND: Infectious diseases constantly represent the source of sickness as well as mortality in human beings. Herbal applications in human life through using plants for antibacterial and anticancer activity have shown the potential medicinal outcome. OBJECTIVES: To evaluate the antibacterial and anticancer activities of the crude extract of Matricaria aurea. MATERIALS AND METHODS: The antibacterial activity of the crude flowers of M. aurea extract was examined against reference and clinical bacterial strains by agar well diffusion method. Minimum inhibitory concentrations and minimum bactericidal concentrations were determined by micro broth dilution assays using MH broth. Herbal extract was employed over human breast adenocarcinoma cell line (MCF-7), hepatocellular carcinoma cell line (HepG-2) and colorectal adenocarcinoma cell line (HCT-116) to optimize cancer cells proliferation by SRB assay. RESULTS: The data has shown that the extract from M. aurea had significant antimicrobial activity against the tested microorganisms. The plant extract showed higher antibacterial activity against the reference strain of Streptococcus pyogenes. The MIC and MBC varied between 0.38-12.5 mg/ml and 3.1-200 mg/ml respectively. Synergy study elucidated the significant bacteriostatic effect of M. aurea extract on S. aureus and S. saprophyticus. The data of SRB assay deliver the potential anticancer activity through cell death. CONCLUSION: This study delivers innovative information that M. aurea possessed excellent bio-activities against pathogenic microbes and cancer cells, which drive attention for further research to explore the active components responsible for biological efficacies.

Flavonol Glycosides: In Vitro Inhibition of DPPIV, Aldose Reductase and Combating Oxidative Stress are Potential Mechanisms for Mediating the Antidiabetic Activity of Cleome droserifolia.

Diabetes is a major health problem that is associated with high risk of various complications. Medicinal plants hold great promise against diabetes. The traditional use of Cleome droserifolia as an antidiabetic agent was correlated to its flavonol glycosides content. In the current study, five major flavonol glycosides appeared on the RP-HPLC chromatogram of the aqueous extract namely; quercetin-3-O-ß-d-glucosyl-7-O-α-rhamnoside (1), isorhamnetin-7-O-ß-neohesperidoside (2), isorhamnetin-3-O-ß-d-glucoside (3) kaempferol-4'-methoxy-3,7-O-α-dirhamnoside (4), and isorhamnetin-3-O-α-(4″-acetylrhamnoside)-7-O-α-rhamnoside (5). The inhibitory activities of these compounds were tested in vitro against several enzymes involved in diabetes management. Only the relatively less polar methoxylated flavonol glycosides (4, 5) showed mild to moderate α-amylase and α-glucosidase inhibitory activities. Compounds 1-4 displayed remarkable inhibition of dipeptidyl peptidase IV (DPPIV) enzyme (IC50 0.194 ± 0.06, 0.573 ± 0.03, 0.345 ± 0.02 and 0.281 ± 0.05 µg/mL, respectively) comparable to vildagliptin (IC50 0.154 ± 0.02 µg/mL). Moreover, these compounds showed high potential in preventing diabetes complications through inhibiting aldose reductase enzyme and combating oxidative stress. Both isorhamnetin glycoside derivatives (2, 3) exhibited the highest activities in aldose reductase inhibition and compound 2 (IC50 5.45 ± 0.26 µg/mL) was even more potent than standard quercetin (IC50 7.77 ± 0.43 µg/mL). Additionally, these flavonols exerted excellent antioxidant capacities through 2, 2-diphenyl-1-picrylhydrazil (DPPH) and ferric reducing antioxidant (FRAP) assays.

Secondary Metabolites of Saussurea costus Leaf Extract Induce Apoptosis in Breast, Liver, and Colon Cancer Cells by Caspase-3-Dependent Intrinsic Pathway.

BACKGROUND: Apoptosis, a major form of programmed cell death, plays a vital role in regulating tissue development and maintenance of homeostasis in eukaryotes. Apoptosis can occur via a death receptor-dependent extrinsic or a mitochondrial-dependent intrinsic pathway and can be induced by various chemotherapeutic agents. In this study, the anticancer activity of Saussurea costus and its mode of intervention in human cancer cells of breast, colon, and liver were investigated. RESULTS: In this study, the bioactives of S. costus leaves were extensively extracted in five solvents of different polarity. The cytotoxicity and anticancer effect of the extracted secondary metabolites were investigated against breast (MCF-7), liver (HepG2), and colon (HCT116) cancer cell lines using a Sulphorhodamine B (SRB) assay. Secondary metabolites extracted using hexane, methanol, ethyl acetate, and chloroform had the highest cytotoxicity and thus the greatest anticancer effect on all the cancer cell lines tested (IC50; ranging from 0.25 to 2.5 µg/ml), while butanol was comparatively less active (IC50; ranging from 23.2 to 25.5 µg/ml). Further investigation using DNA flow cytometry and fluorescent microscopy revealed that the extract arrested the cells in the G1 phase of cell cycle and induced apoptosis. Furthermore, the elevated expression level of proapoptotic proteins and decreased expression level of antiapoptotic proteins confirmed that the intrinsic (mitochondrial) pathway was involved in mediating the apoptosis of cancer cells upon treatment with S. costus extract. These results altogether suggest that S. costus could be a potential anticancer agent. CONCLUSION: These results suggest that the S. costus extract is the potential source of the secondary metabolites that could be used as anticancer agent to treat diverse cancers of breast, colon, and liver.

Black tea and curcumin synergistically mitigate the hepatotoxicity and nephropathic changes induced by chronic exposure to aflatoxin-B1 in Sprague-Dawley rats.

The study aimed to clarify the characteristics of black tea (BTE) and/or curcumin (CMN) against aflatoxin-B1 (AFB1). Forty eight adult male Sprague-Dawley rats were divided into eight groups. G1 was non-treated control. G2, G3, and G4 were olive oil, BTE, and CMN, respectively. G5 was olive oil-dissolved AFB1 (25 µg/kg b.w). G6, G7, and G8 were AFB1 along with BTE (2%), CMN (200 mg/kg b.w.), and BTE plus CMN, respectively. All treatments were orally given for consecutive 90 days. After treatment period, rats were sacrificed. Serobiochemical analysis and histopathology showed hepatorenal dysfunction in response to AFB1. Glutathione-antioxidants were significantly decreased versus increased lipid peroxides (p < .05-.001). AFB1 significantly increased the expression of the antitumor p53, but decreased that of antiapoptotic Bcl2 in liver or kidney tissue, either (p < .05). BTE or CMN ameliorated those changes induced by AFB1 in both liver and kidney with highly pronounced improvement when combined BTE/CMN was used. PRACTICAL APPLICATIONS: Black tea (BTE) and curcumin (CMN) were known for their antioxidant effects, and several studies reported their independent effects against different toxicities including aflatoxicosis. The current study clarifies the ameliorative characteristics of both agents; BTE and/or CMN, against the toxicity resulted from the chronic exposure to aflatoxin-B1 (AFB1) (25 µg/kg b.w. for consecutive 90 days). The dose of either agents, BTE or CMN, was 200 mg/kg b.w. along with AFB1. The pathologic changes, serobiochemical parameters, oxidative stress, histological changes, and the molecular disruption, induced by AFB1 in both liver and kidney were obviously and significantly ameliorated after BTE and/or CMN treatments in variable potencies where both agents showed the most effective antitoxic capacities.

Vitamin E and selenium administration synergistically mitigates ivermectin and doramectin-induced testicular dysfunction in male Wistar albino rats.

Avermectins are broad-spectrum antiparasitic drugs in veterinary and human medication. The current study aimed to examine the toxic effects of ivermectin (IVM) and doramectin (DRM), with or without co-treatment of vitamin E (Vit.E) and selenium (Se) on apoptosis, oxidative stress and male fertility in Wistar rats. Twenty five adult male animals were divided into five groups; G1; was control (CTL) received saline, G2; IVM (0.2 mg/kg b.w), G3; IVM plus Vit.E/Se (80/1.6 mg/kg b.w, respectively), G4; DRM (0.2 mg/kg b.w), and G5; DRM plus Vit.E/Se. Both IVM and DRM were given by subcutaneous (s.c) injections while Vit.E/Se was orally given. All treatments were administered once weekly for four consecutive weeks. By 24 h after the last treatment, the animals were sacrificed. Blood and tissue samples were collected for hematology, serobiochemistry, histopathology, and molecular assays for hepatic/ renal toxicities, oxidative stress, cell viability and fertility parameters. Apoptosis of the hepatic cells obtained from the treated rats was assayed by detection of annexin-V using the flow cytometric assay (FCA). The proliferating cellular nuclear antigen (PCNA) and DNA fragmentation in the treated rats' testicular tissues were also assayed. Moreover, the direct effects of IVM or DRM with or without concomitant administration of Vit.E/Se on testicular cells isolated from adult rat were also performed in vitro. Apoptosis of those cultured testicular cells in response to the different treatments was assayed by detection of the inhibition-concentration fifty (IC50) using the SRB method, and evaluating the viable versus apoptotic cells microscopically after staining with acridine orange-ethidium bromide (AO/EB). In conclusion, both avermectins induced apoptosis in the living and cultured cells, while those antioxidants; Vit.E and Se, reduced the oxidative stress and cytotoxicity both in vivo and in vitro, either. Furthermore, the reprotoxicity and reduced male fertility were seriously evoked by IVM, but not DRM with dramatic ameliorative effect of Vit.E/Se if concomitantly administered. Avermectins, especially ivermectin, should be given according to the dose recommended by the manufacturer company and repeated dosages should be given with Vit.E/Se.

Analgesic, Anti-Inflammatory, Cytotoxic Activity Screening and UPLC-PDA-ESI-MS Metabolites Determination of Bioactive Fractions of Kleinia pendula.

Kleinia pendula (Forssk.) DC. is a prostrate or pendent dark green succulent herb found in the southwestern mountain regions of Saudi Arabia. The literature survey of the plant reveals a lack of phytochemical and pharmacological studies, although traditional uses have been noted. The objective of the present work was to assess the in vivo analgesic and anti-inflammatory activities, as well as, the in vitro cytotoxic potential of the fractions of Kleinia pendula, and correlate these activities to the plant metabolites. The methanolic extract of Kleinia pendula was subjected to fractionation with n-hexane, ethyl acetate, chloroform, n-butanol, and water. The fractions were screened for their analgesic and anti-inflammatory activities, as well as cytotoxic activity against breast, liver, and colon cancer cell lines. The n-hexane and chloroform fractions of Kleinia pendula showed significant cytotoxic activity against all three cancer cell lines tested. The ethyl acetate and chloroform fractions showed significant analgesic and anti-inflammatory activities. The metabolites in these three active fractions were determined using UPLC-PDA-ESI-MS. Thus, the analgesic and anti-inflammatory activities of the plant were attributed to its phenolic acids (caffeoylquinic acid derivatives, protocatechuic, and chlorogenic acids). While fatty acids and triterpenoids such as (tormentic acid) in the hexane fraction are responsible for the cytotoxic activity; thus, these fractions of Kleinia pendula may be a novel source for the development of new plant-based analgesic, anti-inflammatory, and anticancer drugs.