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Hibiscus species (Malvaceae) possess a plethora of appealing pharmacological activities with an extended history of customary use in diverse medical conditions. The present study aimed at comparing the metabolomic analyses of three Hibiscus species native to Egypt, namely H. tiliaceus, H. schizopetalus extract (HSE), and H. rosa-sinensis, alongside identifying a promising natural wound healing candidate. Chemical profiling of the leaf extracts was achieved via UPLC-ESI/MS/MS-guided analysis that resulted in the tentative identification of a total of 48 secondary metabolites pertaining to phenolic acids, flavonoids, anthocyanins, fatty acids, and fatty amides. Remarkably, in vitro studies revealed that HSE exhibited the topmost wound healing activity. Subsequently, HSE was formulated into hydro- and nanogel (1% w/v) formulations for further assessing its efficacy in the wound excision model. HSE-nanogel demonstrated a significant in vivo wound contraction activity alongside improving histopathological abnormalities. Mechanistically, HSE-nanogel upregulated the wound antioxidant status through increasing the levels of reduced glutathione (GSH) and catalase activity. Moreover, HSE-nanogel suppressed the wound inflammatory responses by diminishing the expressions of NF-ĸB, TNF-α, and IL-6. Molecular docking studies were performed on HSE's major constituents using CDOCKER, which further supported the in vivo findings. Collectively, HSE nanogel exhibits notable aptitude as a wound-healing agent, warranting further clinical appraisal.
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BACKGROUND: Moringa oleifera is a highly nutritious plant widely used in traditional medicine. RESULTS: The aroma constituents present in the fresh flowers of M. oleifera versus the hydrodistilled oil and hexane extract were studied using GC-MS. Aldehydes were the major class detected in the fresh flowers (64.75%) with E-2-hexenal being the predominant component constituting > 50%. Alkane hydrocarbons, monoterpenes, and aldehydes constituted > 50% of the hydrodistilled oil, while alkane hydrocarbons exclusively constitute up to 65.48% of the hexane extract with heptacosane being the major component (46.2%). The cytotoxicity of the hexane extract was assessed on RAW 264.7 macrophages using the MTT assay which revealed no significant cytotoxicity at concentrations of 1 µg/mL and displayed IC50 value at 398.53 µg/mL as compared to celecoxib (anti-inflammatory drug) with IC50 value at 274.55 µg/ml. The hexane extract of Moringa flowers displayed good anti-inflammatory activity through suppression of NO, IL-6, and TNF-α in lipopolysaccharide-induced RAW 264.7 macrophages. The total phenolic and flavonoid content in the hexane extract was found to be 12.51 ± 0.28 mg GAE/g extract and 0.16 ± 0.01 mg RuE/g extract, respectively. It displayed moderate antioxidant activity as indicated by the in vitro DPPH, ABTS, CUPRAC, FRAP, and phosphomolybdenum (PBA) assays. No metal chelating properties were observed for the extract. The enzyme inhibitory potential of the hexane extract was evaluated on acetyl- and butyrylcholinesterases (for neuroprotective assessment), α-amylase and α-glucosidase (for antihyperglycemic assessment), and tyrosinase (for dermoprotective assessment) revealing promising results on cholinesterases, tyrosinase, and α-glucosidase. CONCLUSION: Our findings suggested that M. oleifera leaves can be considered as a multidirectional ingredient for preparing functional applications.
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Anti-Inflamatórios , Antioxidantes , Flores , Moringa oleifera , Extratos Vegetais , Camundongos , Animais , Flores/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Moringa oleifera/química , Células RAW 264.7 , Antioxidantes/farmacologia , Antioxidantes/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Odorantes/análiseRESUMO
BACKGROUND: The current study is a retrospective study designed to evaluate changes in complete blood count and coagulation parameters in adult coronavirus disease 2019 (COVID-19) patients at a prominent Saudi tertiary center to predict disease severity and mortality. METHODS: The cohort consisted of 74 800 adult patients divided into four groups based on a COVID-19 test and the patient's sex: 35 985 in the female negative COVID-19 group, 23 278 in the male negative COVID-19 group, 8846 in the female positive COVID-19 group and 6691 in the male positive COVID-19 group. RESULTS: Patients with COVID-19 demonstrated decreased white blood cell counts and increased red blood cell counts. Also, COVID-19-positive participants exhibited more prolonged partial thromboplastin time and lower D-dimer levels than those of COVID-19-negative subjects (p<0.05). The study also revealed gender-dependent impacts on platelet counts, implying a possible relationship with the greater infection mortality rate in men than in women (p<0.001). In addition, the study found a link between changes in coagulation test results and death in COVID-19 patients (p<0.001). The evidence regarding the effects of COVID-19 on blood cell counts and coagulation, on the other hand, is conflicting, most likely due to variances in study populations and the timing of testing postinfection. CONCLUSIONS: According to the findings, COVID-19-related alterations in blood cell count and clotting ability may be risk factors for death.
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Marine endosymbionts have gained remarkable interest in the last three decades in terms of natural products (NPs) isolated thereof, emphasizing the chemical correlations with those isolated from the host marine organism. The current study aimed to conduct comparative metabolic profiling of the marine red algae Corallina officinalis, and three fungal endosymbionts isolated from its inner tissues namely, Aspergillus nidulans, A. flavipes and A. flavus. The ethyl acetate (EtOAc) extracts of the host organism as well as the isolated endosymbionts were analyzed using ultra-high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-MS/MS)in both positive and negative ion modes, applying both full scan (FS) and all ion fragmentation (AIF) modes. Extensive interpretation of the LC-MS/MS spectra had led to the identification of 76 metabolites belonging to different phytochemical classes including alkaloids, polyketides, sesquiterpenes, butyrolactones, peptides, fatty acids, isocoumarins, quinones, among others. Metabolites were tentatively identified by comparing the accurate mass and fragmentation pattern with metabolites previously reported in the literature, as well as bioinformatics analysis using GNPS. A relationship between the host C. officinalis and its endophytes (A. flavus, A. nidulans, and A. flavipes) was discovered. C. officinalis shares common metabolites with at least one of the three endosymbiotic fungi. Some metabolites have been identified in endophytes and do not exist in their host. Multivariate analysis (MVA) revealed discrimination of A. flavipes from Corallina officinalis and other associated endophytic Aspergillus fungi (A. flavus and A. nidulans).
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BACKGROUND: Polyalthia suberosa (Roxb.) Thwaites (Annonaceae) is a medicinal plant that has been reported for its various pharmacological potentials, such as its anti-inflammatory, analgesic, antioxidant, and neuropharmacological activities. This study aimed to analyze the leaf essential oils of P. suberosa (PSLO) collected in different seasons, to evaluate the acetylcholinesterase inhibitory activity, and to corroborate the obtained results via in-silico molecular docking studies. METHODS: The leaf essential oils of P. suberosa collected in different seasons were analyzed separately by GC/MS. The acetylcholinesterase inhibitory activity of the leaves oil was assessed via colorimetric assay. In-silico molecular docking studies were elucidated by virtual docking of the main compounds identified in P. suberosa leaf essential oil to the active sites in human acetylcholinesterase crystal structure. RESULTS: A total of 125 compounds were identified where D-limonene (0.07 - 24.7%), α-copaene (2.25 - 15.49%), E-ß-caryophyllene (5.17 - 14.42%), 24-noroleana-3,12-diene (12.92%), ß-pinene (0.14 - 8.59%), and α-humulene (2.49-6.9%) were the most abundant components. Results showed a noteworthy influence of the collection season on the chemical composition and yield of the volatile oils. The tested oil adequately inhibited acetylcholinesterase enzyme with an IC50 value of 91.94 µg/mL. Additionally, in-silico molecular docking unveiled that palmitic acid, phytol, p-cymene, and caryophyllene oxide demonstrated the highest fitting scores within the active sites of human acetylcholinesterase enzyme. CONCLUSIONS: From these findings, it is concluded that P. suberosa leaf oil should be evaluated as a food supplement for enhancing memory.
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Óleos Voláteis , Polyalthia , Humanos , Estações do Ano , Acetilcolinesterase , Óleos Voláteis/farmacologia , Simulação de Acoplamento Molecular , Anti-Inflamatórios não EsteroidesRESUMO
The doping of engineered nanomaterials (ENMs) is a key tool for manipulating the properties of ENMs (e.g., electromagnetic, optical, etc.) for different therapeutic applications. However, adverse health outcomes and the cellular biointeraction of doped ENMs, compared to undoped counterparts, are not fully understood. Previously, we have shown that doping manganese oxide nanoparticles with ZnO (ZnO-MnO2 NPs) improved their catalytic properties. In this study, we assessed the toxicity of ZnO-MnO2 NPs in Raw 264.7 cells. NPs were prepared via an eco-friendly, co-precipitation method and characterized by several techniques, including transmission and scanning electron microscopy, X-ray diffraction, and Fourier transform infrared. The physicochemical properties of ZnO-MnO2 NPs, including size, morphology, and crystalline structure, were almost identical to MnO2 NPs. However, ZnO-MnO2 NPs showed slightly larger particle aggregates and negative charge in cell culture media. Exposure to ZnO-MnO2 NPs resulted in lower toxicity based on the cell viability and functional assay (phagocytosis) data. Exposure to both NPs resulted in the activation of the cell inflammatory response and the generation of reactive oxygen species (ROS). Despite this, exposure to ZnO-MnO2 NPs was associated with a lower toxicity profile, and it resulted in a higher ROS burst and the activation of the cell antioxidant system, hence indicating that MnO2 NP-induced toxicity is potentially mediated via other ROS-independent pathways. Furthermore, the cellular internalization of ZnO-MnO2 NPs was lower compared to MnO2 NPs, and this could explain the lower extent of toxicity of ZnO-MnO2 NPs and suggests Zn-driven ROS generation. Together, the findings of this report suggest that ZnO (1%) doping impacts cellular biointeraction and the consequent toxicological outcomes of MnO2 NPs in Raw 264.7 cells.
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Obesity and its comorbidities represent a major health problem worldwide. Treatment by reducing food intake and physical activity interventions has limited success especially with elderly people with chronic diseases. Nutraceuticals are naturally originated and successfully used for their physiological and nutritional benefit in health care. They might be alternative means to help lose weight and reduce obesity-associated metabolic disorders with the improvement of health, delay the aging process, prevention of chronic diseases, increase of life expectancy, or support to the structure or function of the body. The current study enumerates the inherent role of nutraceuticals in the management of obesity and its related comorbidities. The study is supported with the molecular docking studies discussing the mechanism of action. An attempt to optimize the role of nutraceuticals is made in this article in addition to widen the scope of its use in this chronic worldwide disease.
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Suplementos Nutricionais , Obesidade , Humanos , Idoso , Simulação de Acoplamento Molecular , Estudos Prospectivos , Obesidade/terapia , Doença CrônicaRESUMO
Aging or senescence is part of human life development with many effects on the physical, mental, and physiological aspects which may lead to age-related deterioration in many organs. Genus Curcuma family Zingieraceae represents one of the well-studied and medically important genera with more than eighty species. The genus is reported to contain different classes of biologically active compounds that are mainly presented in diphenylheptanoids, diphenylpentanoids, diphenylalkanoids, phenylpropene derivatives, alkaloids, flavonoids, chromones, terpenoids, phenolic acids and volatile constituents. Rhizomes and roots of such species are rich with main phytoconstituents viz. curcumin, demethoxycurcumin and bis-demethoxycurcumin. A wide variety of biological activities were demonstrated for different extracts and essential oils of genus Curcuma members including antioxidant, anti-inflammatory, cytotoxic and neuroprotective. Thus, making them as an excellent safe source for nutraceutical products and as a continuous promising area of research on lead compounds that may help in the slowing down of the aging process especially the neurologic and mental deterioration that are usually experienced upon aging. In this review different species of the genus Curcuma were summarized with their phytochemical and biological activities highlighting their role as antiaging agents. The data were collected from different search engines viz. Pubmed®, Google Scholar®, Scopus® and Web of Science® limiting the search to the period between 2003 up till now.
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Alcaloides , Diarileptanoides , Fitoterapia , Humanos , Curcuma/química , Etnofarmacologia , Alcaloides/químicaRESUMO
The emergence of multi-drug-resistant microbial strains spurred the search for antimicrobial agents; as a result, two distinct approaches were combined: four inâ vitro studies and four corresponding molecular docking investigations. Antituberculosis, anti-methicillin-resistant Staphylococcus aureus (anti-MRSA), antifungal, and larvicidal activities of the crude extract, two fractions, and seven isolated compounds from Aspergillus terreus derived from Morus alba roots were explored. The isolated compounds (5 butyrolactones and 2 orsellinic acid derivatives) showed potent to moderate antitubercular activity with MIC values ranging from 1.95 to 62.5â µg/mL (compared to isoniazid, 0.24â µg/mL) and promising anti-MRSA potential with inhibition zone diameters ranging from 8 to 25â mm. Additionally, the in silico study proved that the isolated compounds bind to the two corresponding proteins' active sites with high to moderate -(C-Docker interaction energies) and stable interactions. The isolated compounds displayed antifungal activities against different fungal strains at diverse degrees of activity, among them compound (8"S,9")-dihydroxy-dihydrobutyrolactone I eliciting the best antifungal activity. Meanwhile, all isolated compounds, fractions, and the crude extract demonstrated extremely selective potent to moderate activity against Cryptococcus neoformans. The isolated five butyrolactone derivatives could develop potential mosquito larvicidal agents as a result of promising docking outcomes in the larval enzyme carboxylesterase.
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Anti-Infecciosos , Aspergillus , Staphylococcus aureus Resistente à Meticilina , Morus , Resorcinóis , Animais , Antifúngicos/farmacologia , Simulação de Acoplamento Molecular , Testes de Sensibilidade Microbiana , Anti-Infecciosos/farmacologia , Fungos , Misturas Complexas , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
The steady increase in the use of electronic cigarettes (ECs) has reached an epidemic level, increasing mortality and morbidity, mainly due to pulmonary toxicity. Several mechanisms are involved in EC-induced toxicity, including oxidative stress and increased inflammation. Concurrently, the integrity of cellular metabolism is essential for cellular homeostasis and mitigation of toxic insults. However, the effects of EC on cellular metabolism remain largely unknown. In this study, we investigated the metabolic changes induced by EC in human lung epithelial cells (A549) using an untargeted metabolomics approach. A549 cells were exposed to increasing EC vapor extract concentrations, and cell viability, oxidative stress, and metabolomic changes were assessed. Our findings show that ECs induce cell death and increase oxidative stress in a concentration-dependent manner. Metabolomic studies demonstrated that ECs induce unique metabolic changes in key cellular metabolic pathways. Our results revealed that exposure to ECs induced clear segregation in metabolic responses which is driven significantly by number of essential metabolites such as aminoacids, fatty acids, glutathione, and pyruvate. Interstingly, our metabolomics results showed that each concentration of ECs induced unqiues pattern of metabolic changes, suggesting the complexity of ECs induced cytotoxcity. Disrupted metabolites were linked to essential cellular pathways, such as fatty acid biosynthesis, as well as glutathione, pyruvate, nicotinate and nicotinamide, and amino acid metabolisms. These results highlight the potential adverse effects of ECs on cellular metabolism and emphasize the need for further research to fully understand the long-term consequences of EC use. Overall, this study demonstrates that ECs not only induce cell death and oxidative stress but also disrupt cellular metabolism in A549 lung epithelial cells.
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This study aims to investigate the phytoconstituents of the chloroform fraction of three Cystoseira spp. namely C. myrica, C. trinodis, and C. tamariscifolia using UPLC/ESI/MS technique. The results revealed the identification of 19, 20 and 11 metabolites in C. myrica, C. trinodis, and C. tamariscifolia, respectively mainly terpenoids, flavonoids, phenolic acids and fatty acids. Also, an in vitro antioxidant study using FRAP and DPPH assays was conducted where the chloroform fraction of C. trinodis displayed the highest antioxidant activity in both assays, which would be attributed to its highest total phenolics and total flavonoids. Besides, the investigation of COX-1, α-glucosidase and α-amylase inhibitory activities were performed. Regarding C. trinodis, it showed the strongest inhibitory activity towards COX-1. Moreover, it showed potent inhibitory activity towards α-glucosidase and α-amylase enzymes. According to the molecular docking studies, the major compounds characterised showed efficient binding to the active sites of the target enzymes.
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Clorofórmio , alfa-Glucosidases , Simulação de Acoplamento Molecular , Cromatografia Líquida de Alta Pressão , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antioxidantes/farmacologia , Antioxidantes/química , Flavonoides/química , alfa-AmilasesRESUMO
Ascariasis and intestinal parasitic nematodes are the leading cause of mass mortality infecting many people across the globe. In light of the various deleterious side effects of modern chemical-based allopathic drugs, our preferences have currently shifted towards the use of traditional plant-based drugs or botanicals for treating diseases. The defensive propensities in the botanicals against parasites have probably evolved during their co-habitation with parasites, humans and plants in nature and hence their combative interference in one another's defensive mechanisms has occurred naturally ultimately being very effective in treating diseases. This article broadly outlines the utility of plant-based compounds or botanicals prepared from various medicinal herbs that have the potential to be developed as effective therapies against the important parasites causing ascariasis and intestinal hookworm infections leading to ascariasis & infections and thereby human mortality, wherein allopathic treatments are less effective and causes enormous side-effects.
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The global COVID-19 pandemic has strained healthcare systems around the globe, necessitating extensive research into the variables that affect patient outcomes. This study examines the relationships between key haematology parameters, duration of hospital stay (LOS), and mortality rates in COVID-19 cases in paediatric patients. Researchers analyse relationships between independent variables (COVID-19 status, age, sex) and dependent variables (mortality, LOS, coagulation parameters, WBC count, RBC parameters) using multivariate regression models. Although the R-square values (0.6-3.7%) indicate limited explanatory power, coefficients with statistical significance establish the impact of independent variables on outcomes. Age emerges as a crucial predictor of mortality; the mortality rate decreases by 1.768% per age group. Both COVID-19 status and age have an inverse relationship with length of stay, emphasising the milder hospitalisation of children. Platelet counts decline with age and male gender, potentially revealing the influence of COVID-19 on haematological markers. There are significant correlations between COVID-19 status, age, gender and coagulation measures. Lower prothrombin time and D-dimer concentrations in elder COVID-19 patients are indicative of distinct coagulation profiles. WBC and RBC parameters exhibit correlations with variables: COVID-19-positive patients have lower WBC counts, whereas male COVID-19-positive patients have higher RBC counts. In addition, correlations exist between independent variables and the red cell distribution width, mean corpuscular volume, and mean corpuscular haemoglobin. However, there is no correlation between mean corpuscular haemoglobin concentration and outcomes, indicating complex interactions between haematological markers and outcomes. In essence, this study underlines the importance of age in COVID-19 mortality, provides novel insights into platelet counts, and emphasises the complexity of the relationships between haematological parameters and disease outcomes.
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The genus Eremophila, despite comprising more than 250 species, has scarce literature studies that could be traced concerning the chemical profile and bioactivity of Eremophila purpurascens. The current study targets the investigation of the in vitro and in vivo anti-oxidant, anti-hyperglycemic, and hepatoprotective potential of the polyphenol-rich leaf extract of E. purpurascens (EP). EP showed promising total anti-oxidant capacity with IC50 values of 106 and 114 µg/mL in 2,2'-azinobis [3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt (ABTS) and diphenyl-1-picrylhydrazyl (DPPH) assays, respectively, with total anti-oxidant capacities of 331, 245, and 1767 µmol/g in ABTS, DPPH, and ferric reducing anti-oxidant power assays, respectively. In HepG2 cells, pre-treated with CCl4, a dose of 100 µg/mL EP ameliorated the reduced superoxide dismutase and glutathione levels and total anti-oxidant capacity with values of 312.5 U/mL, 15.47 mg/dL, and 1.03 nmol/mL, respectively. In vitro anti-diabetic evaluation using 3T3-L1 adipocyte culture showed that at a dose of 30 µg/mL, the EP extract elicited a 6.3% decrease in the concentration of glucose (22.4 mmol/L), showing significant amelioration with regard to pioglitazone and insulin. EP also demonstrated elevated serum insulin by 77.78% with a marked reduction in fasting blood glucose level by 64.55% relative to the streptozotocin diabetic rats in vivo. EP also relieved the liver stress markers both in vitro in CCl4 and in vivo in tamoxifen (TAM) models. EP markedly decreased TAM toxicity, as demonstrated by the decline in the liver stress markers, ALT and AST, by 36.1 and 51.1%, respectively. It also relieved the oxidative stress triggered by TAM, as revealed by the reduction in the levels of TBARs and TNF-α by 21.4 and 40%, respectively. Liquid chromatography electrospray ionization mass spectrometry of EP revealed a total of twelve peaks belonging to phenylpropanoids, lignans, and phenolics, where verbascoside and pinoresinol-4-O-ß-d-glucoside represented the most abundant secondary metabolites. The docking experiment showed that tri-O-galloyl-hexoside had the best fitting within the NADPH oxidase active sites with binding energy (ΔG = -81.12 kcal/mol). Thus, the plant can be of beneficial value in the control of hyperglycemia in diabetic patients, besides its prophylactic potential against hepatic complications.
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Uveitis is an ocular illness that if not treated properly can lead to a total loss of vision. In this study, we evaluated the utility of HA-coated Dexamethasone-sodium-phosphate (DEX)-chitosan nanoparticles (CSNPs) coated with hyaluronic acid (HA) as a sustained ocular delivery vehicle for the treatment of endotoxin-induced-uveitis (EIU) in rabbits. The CSNPs were characterized for particle size, zeta potential, polydispersity, surface morphology, and physicochemical properties. Drug encapsulation, in vitro drug release, and transcorneal permeation were also evaluated. Finally, eye irritation, ocular pharmacokinetics, and pharmacodynamics were in vivo. The CSNPs ranged from 310.4 nm and 379.3 nm pre-(uncoated) and post-lyophilization (with HA-coated), respectively. The zeta potentials were +32 mV (uncoated) and -5 mV (HA-uncoated), while polydispersity was 0.178-0.427. Drug encapsulation and loading in the CSNPs were 73.56% and 6.94% (uncoated) and 71.07% and 5.54% (HA-coated), respectively. The in vitro DEX release over 12 h was 77.1% from the HA-coated and 74.2% from the uncoated NPs. The physicochemical properties of the CSNPs were stable over a 3-month period when stored at 25 °C. Around a 10-fold increased transcorneal-flux and permeability of DEX was found with HA-CSNPs compared to the DEX-aqueous solution (DEX-AqS), and the eye-irritation experiment indicated its ocular safety. After the ocular application of the CSNPs, DEX was detected in the aqueous humor (AH) till 24 h. The area under the concentrations curve (AUC0-24h) for DEX from the CSNPs was 1.87-fold (uncoated) and 2.36-fold (HA-coated) higher than DEX-AqS. The half-life (t1/2) of DEX from the uncoated and HA-coated NPs was 2.49-and 3.36-fold higher, and the ocular MRT0-inf was 2.47- and 3.15-fold greater, than that of DEX-AqS, respectively. The EIU rabbit model showed increased levels of MPO, TNF-α, and IL-6 in AH. Topical DEX-loaded CSNPs reduced MPO, TNF-α, and IL-6 levels as well as inhibited NF-κB expression. Our findings demonstrate that the DEX-CSNPs platform has improved the delivery properties and, hence, the promising anti-inflammatory effects on EIU in rabbits.
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The incorporation of engineered nanomaterials (ENMs) in biomedical and consumer products has been growing, leading to increased human exposure. Previous research was largely focused on studying direct ENM toxicity in unrealistic high-exposure settings. This could result in overlooking potential adverse responses at low and subtoxic exposure levels. This study investigated adverse cellular outcomes to subtoxic concentrations of zinc oxide (ZnONPs) or nickel oxide (NiONPs) nanoparticles in the Raw 264.7 cells, a macrophage-like cell model. Exposure to both nanoparticles resulted in a concentration-dependent reduction of cell viability. A subtoxic concentration of 6.25 µg/mL (i.e., no observed adverse effect level) was used in subsequent experiments. Exposure to both nanoparticles at subtoxic levels induced reactive oxygen species generation. Cellular internalization data demonstrated significant uptake of NiONPs, while there was minimal uptake of ZnONPs, suggesting a membrane-driven interaction. Although subtoxic exposure to both nanoparticles was not associated with cell activation (based on the expression of MHC-II and CD86 surface markers), it resulted in the modulation of the lipopolysaccharide-induced inflammatory response (TNFα and IL6), and cells exposed to ZnONPs had reduced cell phagocytic capacity. Furthermore, subtoxic exposure to the nanoparticles distinctly altered the levels of several cellular metabolites involved in cell bioenergetics. These findings suggest that exposure to ENMs at subtoxic levels may not be devoid of adverse health outcomes. This emphasizes the importance of establishing sensitive endpoints of exposure and toxicity beyond conventional toxicological testing.
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BACKGROUND: Endophytic Aspergillus species produce countless valuable bioactive secondary metabolites. In the current study, Aspergillus flavus an endophyte from the soft coral Sarcophyton ehrenbergi was chemically explored and the extracted phytoconstituents were subsequently evaluated for antimicrobial activity. This is accomplished by employing nuclear magnetic resonance (NMR) spectroscopy and computational techniques. Additionally, An in vitro anticancer analysis of A. flavus total extract against breast cancer cells (MCF-7) was investigated. RESULT: Six compounds were separated from the crude alcohol extract of the endophytic Aspergillus flavus out of which anhydro-mevalonolactone was reported for the first time. The anti-fungal and anti-Helicobacter pylori properties of two distinct compounds (Scopularides A and B) were assessed. Additionally, computational research was done to identify the binding mechanisms for all compounds. Both the compounds were found to be active against H. pylori with minimum inhibitory concentration (MIC) values ranging from 7.81 to 15.63 µg/ mL as compared with clarithromycin 1.95 µg/ mL. Scopularides A was potent against both Candida albicans and Aspergillus niger with MIC values ranging from 3.9 to 31.25 µg/ mL, while scopularides B only inhibits Candida albicans with MIC value of 15.63 µg/ mL and weak inhibitory activity against A. niger (MIC = 125 µg/ mL). Furthermore, cytotoxic activity showed a significant effect (IC50: 30.46 mg/mL) against MCF-7 cells. CONCLUSION: Our findings report that cytotoxic activity and molecular docking support the antimicrobial activity of Aspergillus flavus, which could be a promising alternative source as a potential antimicrobial agent.
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The study presents antioxidant, phytochemical, anti-proliferative, and gene repression activities against Hypoxia-inducible factor (HIF-1) alpha and Vascular endothelial growth factor (VEGF) of Elaeocarpus sphaericus extract. Elaeocarpus sphaericus dried and crushed plant leaves were extracted using water and methanol by ASE (Accelerated Solvent Extraction) method. Total phenolic content (TPC) and total flavonoid content (TFC) were used to measure the extracts' phytochemical activity (TFC). Antioxidant potential of the extracts was measured through DPPH, ABTS, FRAP, and TRP. Methanolic extract of the leaves of E.â sphaericus has shown a higher amount of TPC (94.666±4.040â mg/gm GAE) and TFC value (172.33±3.21â mg/gm RE). The antioxidant properties of extracts in the yeast model (Drug Rescue assay) showed promising results. Ascorbic acid, gallic acid, hesperidin, and quercetin were found in the aqueous and methanolic extracts of E.â sphaericus at varying amounts, according to a densiometric chromatogram generated by HPTLC analysis. Methanolic extract of E.â sphaericus (10â mg/ml) has shown good antimicrobial potential against all bacterial strains used in the study except E.â coli. The anticancer activity of the extract in HeLa cell lines ranged from 77.94±1.03 % to 66.85±1.95 %, while it ranged from 52.83±2.57 % to 5.44 % in Vero cell lines at varying concentration (1000â µg/ml-31.2â µg/ml). A promising effect of extract was observed on the expression activity of HIF-1 and VEGF gene through RT-PCR assay.
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Antioxidantes , Elaeocarpaceae , Humanos , Antioxidantes/química , Fator A de Crescimento do Endotélio Vascular/genética , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Células HeLa , Escherichia coli , Flavonoides/análise , Metanol , Fenóis/farmacologia , Fenóis/análise , Compostos FitoquímicosRESUMO
In-depth chemical investigation of an ethyl acetate extract of Aspergillus sp. isolated from the soft coral Sinularia species resulted in the isolation of one new meroterpenoid, austalide Z (1), one known austalide W (2), six known prenylated indole diketopiperazine alkaloids (3-8), and phthalic acid and its ethyl derivative (9-10). The structures were established by means of 1D and 2D NMR (one- and two-dimensional nuclear magnetic resonance) experiments supported by UV analysis and ESI-MS (electrospray ionization mass spectrometry). In vitro cytotoxic evaluation was performed against the Caco-2 cancer cell line using the MTT assay, which showed that the examined compounds had weak to moderate activities, with the new meroterpenoid austalide Z (1) displaying an IC50 value of 51.6 µg mL-1. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) predication performed in silico showed that most of the isolated compounds possessed reasonable pharmacokinetic, pharmacodynamic, and toxicity properties. Thus, it can be concluded that Aspergillus sp. could act as a source of drug leads for cancer prevention with promising pharmacokinetic and pharmacodynamic properties and thus could be incorporated in pharmaceutical dosage forms.
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Alzheimer's disease (AD) is a major health problem. Cholinergic transmission is greatly affected in AD. Phytochemical investigation of the alkaloid rich fraction (AF) of Erythrina corallodendron L leaves resulted in isolation of five known alkaloids: erysodine, erythrinine, 8-oxoerythrinine, erysovine N-oxide and erythrinine N-oxide. In this study, eysovine N-oxide was reported for the second time in nature. AF was assayed for cholinesterase inhibition at the concentration of 100â µg mL-1 . AF showed a higher percent inhibition for butyrylcholinesterase enzyme (BuChE) (83.28 %) compared to acetylcholinesterase enzyme (AChE) (64.64 %). The isolated alkaloids were also assayed for their anti-BuChE effect. In-silico docking study was done for the isolated compounds at the binding sites of AChE and BuChE to determine their binding pattern and interactions, also molecular dynamics were estimated for the compound displaying the best fit for AChE and BuChE. In addition, ADME parameters and toxicity were predicted for the isolated alkaloids compared to donepezil.