LC-ESI-MS/MS-Based Comparative Metabolomic Study, Antioxidant and Antidiabetic Activities of Three Lobelia Species: Molecular Modeling and ADMET Study.

The hydroethanol (70%) extracts of three Lobelia species (L. nicotianifolia, L. sessilifolia, and L. chinensis) were analyzed using LC-ESI-MS/MS. Forty-five metabolites were identified, including different flavonoids, coumarin, polyacetylenes, and alkaloids, which were the most abundant class. By applying Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) based on LC-ESI-MS/MS analysis, the three species were completely segregated from each other. In addition, the three Lobelia extracts were tested for their antioxidant activities using a DPPH assay and as antidiabetic agents against α-glycosidase and α-amylase enzymes. L. chinensis extract demonstrated significant antioxidant activity with an IC50 value of 1.111 mg/mL, while L. nicotianifolia showed mild suppressing activity on the α-glycosidase activity with an IC50 value of 270.8 µg/mL. A molecular simulation study was performed on the main compounds to predict their potential antidiabetic activity and pharmacokinetic properties. The molecular docking results confirmed the α-glycosidase inhibitory activity of the tested compounds, as seen in their binding mode to the key amino acid residues at the binding site compared to that of the standard drug acarbose. Furthermore, the predictive ADMET results revealed good pharmacokinetic properties of almost all of the tested compounds. The biological evaluation results demonstrated the promising activity of the tested compounds, aligned with the in silico results.

Silver nanoparticles improve the fungicidal properties of Rhazya stricta decne aqueous extract against plant pathogens.

One of the most promising, non-toxic, and biocompatible developments for many biological activities is the green synthesis of nanoparticles from plants. In this work, we investigated the antifungal activity of silver nanoparticles (AgNPs) biosynthesized from Rhazya stricta aqueous extract against several plant pathogenic fungi. UV-visible spectroscopy, Zeta potential analysis, Fourier-transform infrared spectroscopy (FTIR), and transmitted electron microscopy (TEM) were used to analyze the biosynthesized AgNPs. Drechslera halodes, Drechslera tetramera, Macrophomina phaseolina, Alternaria alternata, and Curvularia australiensis were tested for their potential antifungal activity. Surface Plasmon Resonance (SPR) of Aq. AgNPs and Alkaline Aq. AgNPs was observed at 405 nm and 415 nm, respectively. FTIR analysis indicated hydroxyl, nitrile, amine, and ketone functional groups. Aq. AgNPs and Alka-line Aq. AgNPs had velocities of - 27.7 mV and - 37.9 mV and sizes of 21-90 nm and 7.2-25.3 nm, respectively, according to zeta potential studies and TEM. The antifungal examination revealed that all species' mycelial development was significantly inhibited, accompanied by severe ultra-structural alterations. Among all treatments, Aq. AgNPs were the most effective fungicide. M. phaseolina was statistically the most resistant, whereas A. alternata was the most vulnerable. To the best of our knowledge, this is the first report on R. stricta's antifungal activity against these species.

Advanced polymeric metal/metal oxide bionanocomposite using seaweed Laurencia dendroidea extract for antiprotozoal, anticancer, and photocatalytic applications.

Background: Biosynthesized nanoparticles are gaining popularity due to their distinctive biological applications as well as bioactive secondary metabolites from natural products that contribute in green synthesis. Methodology: This study reports a facile, ecofriendly, reliable, and cost-effective synthesis of silver nanoparticles (AgNPs), copper oxide nanoparticles (CuONPs), and polymeric PVP-silver-copper oxide nanocomposite using ethanol extract of seaweed Laurencia dendroidea and were evaluated for antiprotozoal, anticancer and photocatalytic potential. The nanostructures of the AgNPs, CuONPs, and polymeric PVP-Ag-CuO nanocomposite were confirmed by different spectroscopic and microscopic procedures. Results: The UV-vis spectrum displayed distinct absorption peaks at 440, 350, and 470 nm for AgNPs, CuONPs, and polymeric Ag-CuO nanocomposite, respectively. The average particles size of the formed AgNPs, CuONPs, and Ag-CuO nanocomposite was 25, 28, and 30 nm, respectively with zeta potential values -31.7 ± 0.6 mV, -17.6 ± 4.2 mV, and -22.9 ± 4.45 mV. The microscopic investigation of biosynthesized nanomaterials revealed a spherical morphological shape with average crystallite sizes of 17.56 nm (AgNPs), 18.21 nm (CuONPs), and 25.46 nm (PVP-Ag-CuO nanocomposite). The antiprotozoal potential of green synthesized nanomaterials was examined against Leishmania amazonensis and Trypanosoma cruzi parasites. The polymeric PVP-Ag-CuO nanocomposite exerted the highest antiprotozoal effect with IC50 values of 17.32 ± 1.5 and 17.48 ± 4.2 µM, in contrast to AgNPs and CuONPs. The anticancer potential of AgNPs, CuONPs, and polymeric PVP-Ag-CuO nanocomposite against HepG2 cancer cell lines revealed that all the nanomaterials were effective and the highest anticancer potential was displayed by PVP-Ag-CuO nanocomposite with IC50 values 91.34 µg mL-1 at 200 µg mL-1 concentration. Additionally, PVP-Ag-CuO nanocomposite showed strong photocatalytic effect. Conclusion: Overall, this study suggested that the biogenic synthesized nanomaterials AgNPs, CuONPs, and polymeric PVP-Ag-CuO nanocomposite using ethanol extract of seaweed L. dendroidea possesses promising antiprotozoal anticancer and photocatalytic effect and could be further exploited for the development of antiprotozoal and anticancer therapeutics agents.

GC-MS Chemical Profiling, Biological Investigation of Three Salvia Species Growing in Uzbekistan.

Salvia is a potentially valuable aromatic herb that has been used since ancient times. The present work studied the chemical profile of three Salvia species essential oils (EO): S. officinalis, S. virgata and S. sclarea, as well as assessing their antioxidant and enzyme inhibitory activities. A total of 144 compounds were detected by GC-MS analysis, representing 91.1, 84.7 and 78.1% in S. officinalis, S. virgata and S. sclarea EOs, respectively. The major constituents were cis-thujone, 2,4-hexadienal and 9-octadecenoic acid, respectively. The principal component analysis (PCA) score plot revealed significant discrimination between the three species. The antioxidant activity of the EOs was evaluated using in vitro assays. Only S. virgata EO showed antioxidant activity in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay (26.6 ± 1.60 mg Trolox equivalent (TE)/g oil). Moreover, this oil exhibited the highest antioxidant activity in 2,2-azino bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric-reducing antioxidant capacity (CUPRAC) and ferric-reducing power (FRAP) assays in comparison with the other two EOs (190.1 ± 2.04 vs. 275.2 ± 8.50 and 155.9 ± 1.33 mg TE/g oil, respectively). However, S. virgata oil did not show any effect in the chelating ability assay, while in the PBD assay, S. officinalis had the best antioxidant activity (26.4 ± 0.16 mmol TE/g oil). Enzyme inhibitory effect of the EOs was assessed against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), tyrosinase, α-glucosidase and α-amylase. AChE enzyme was more sensitive to S. officinalis EO (4.2 ± 0.01 mg galantamine equivalent (GALAE)/g oil), rather than S. virgata EO, which was ineffective. However, S. virgata had the highest BChE effect (12.1 ± 0.16 mg GALAE/g oil). All studied oils showed good tyrosinase inhibitory activity, ranging between 66.1 ± 0.61 and 128.4 ± 4.35 mg kojic acid equivalent (KAE)/g oil). Moreover, the EOs did not exhibit any glucosidase inhibition and were weak or inefficient on amylase enzyme. Partial least squares regression (PLS-R) models showed that there is an excellent correlation between the antioxidant activity and the volatile profile when being compared to that of enzyme inhibitory activity. Thus, the studied Salvia essential oils are interesting candidates that could be used in drug discovery for the management of Alzheimer's and hyperpigmentation conditions.

Identification and Characterization of Natural and Semisynthetic Quinones as Aurora Kinase Inhibitors.

Aurora kinases (Aurora A, B, and C) are a family of serine/threonine kinases that play critical roles during mitotic initiation and progression. Aurora A and B kinases are ubiquitously expressed, and their overexpression and/or amplification in many cancers have been associated with poor prognosis. Several inhibitors that target Aurora kinases A, B, or both have been developed during the past decade with efficacy in different in vitro and in vivo models for a variety of cancers. Recent studies have also identified Aurora A as a synthetic lethal target for different tumor suppressors, including RB1, SMARCA4, and ARID1A, which signifies the need for Aurora-A-selective inhibitors. Here, we report the screening of a small library of quinones (nine naphthoquinones, one orthoquinone, and one anthraquinone) in a biochemical assay for Aurora A kinase that resulted in the identification of several quinones as inhibitors. IC50 determination against Aurora A and B kinases revealed the inhibition of both kinases with selectivity toward Aurora A. Two of the compounds, natural quinone naphthazarin (1) and a pseudo anthraquinone, 2-(chloromethyl)quinizarin (11), potently inhibited the proliferation of various cancer cell lines with IC50 values ranging from 0.16 ± 0.15 to 1.7 ± 0.06 and 0.15 ± 0.04 to 6.3 ± 1.8 µM, respectively. Treatment of cancer cells with these compounds for 24 h resulted in abrogated mitosis and apoptotic cell death. Direct binding of both the compounds with Aurora A kinase was also confirmed through STD NMR analysis. Docking studies predicted the binding of both compounds to the ATP binding pocket of Aurora A kinase. We have, therefore, identified quinones as Aurora kinase inhibitors that can serve as a lead for future drug discovery endeavors.

Correlation of Glucosinolates and Volatile Constituents of Six Brassicaceae Seeds with Their Antioxidant Activities Based on Partial Least Squares Regression.

Brassicaceae comprises various species representing an economically important source of industrial or pharmaceutical crops. The present study aimed to identify glucosinolates (GSLs) and volatile compounds in six Brassicaceae seeds cultivated in Egypt. An (High Performance Liquid Chromatography-Photodiode Array) HPLC-PDA analysis of GSLs in the alcoholic extracts of Raphanus raphanistrum L. (Rr), Raphanus sativus L. (Rs), Brassica oleracea var. capitata L. (Boc), Brassica oleracea var. botrytis L. (Bob), Brassica rapa L. (Br), and Eruca sativa L. (Es) was carried out using a mixture of 23 standard GSLs. Nineteen GSLs were detected in the studied seeds. Rs had the highest GSL content (135.66 µmol/g Dry weight, DW), while Boc had the lowest GSL content (93.66 µmol/g DW). Glucobrassicin was the major identified compound in Rr, Rs, and Bob. Its highest content was in Rs (28.96 µmol/g DW). Sinigrin was the major identified GSL in Boc (18.02 µmol/g DW), although present with higher content in Bob (22.02 µmol/g DW). Neoglucobrassicin was the major GSL in Br (30.98 µmol/g DW), while glucoerucin was the major GSL in Es (17.84 µmol/g DW). The yields of the steam-distilled oils of the studied seeds ranged between 3.25 ± 0.36 and 9.68 ± 0.25% v/w. A GC-MS analysis of the oils could detect 3, 23, 18, 16, 7, and 9 compounds in Rr, Rs, Boc, Bob, Br, and Es oils, respectively. Sulfur and nitrogenous compounds predominated in all studied oils except Rs, which contained a higher percentage of alkanes. The major identified compound in Rr oil was 4-isothiocyanato-1-(methylthio)-1-butene (94.77 ± 1.25%), while in Br it was 3-butenyl isothiocyanate (69.55 ± 1.02%), thiolane in Rs (15.15 ± 0.22%), and erucin in Es (97.02 ± 1.514%). Both Boc and Bob had the same major compound 4-(methylthio) butanenitrile, which represented 40.35 ± 1.15 and 50.52 ± 1.02% in both oils, respectively. Radical scavenging activity for both GSL extracts and essential oils on DPPH radical ranged between 18.01 ± 0.72 and 114.28 ± 1.15 µg/mL (IC50). The highest antioxidant capacity was for Es oil, while the lowest one was for Rr oil. Generally, it was observed that the GSLs had better antioxidant activity than their corresponding essential oils except for Es oil, which had higher activity. A principal component analysis (PCA) was successfully applied to discriminate among six Brassicaceae seeds based on both HPLC and GC-MS, where complete segregation was achieved among all samples with high correlation between Boc and Bob. Partial Least Squares-Regression (PLS-R) models showed that there is a better correlation between the antioxidant activity and glucosinolate profile when being compared to that of a volatile one. This profiling and variation of GSLs and volatile metabolites of the studied Brassicaceae seeds may be employed in further studies regarding their health-promoting properties.

Chemometric Analysis Based on GC-MS Chemical Profiles of Three Stachys Species from Uzbekistan and Their Biological Activity.

The chemical composition of the essential oils (EOs) of Stachys byzantina, S. hissarica and S. betoniciflora growing in Uzbekistan were determined, and their antioxidant and enzyme inhibitory activity were assessed. A gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of 143 metabolites accounting for 70.34, 76.78 and 88.63% of the total identified components of S. byzantina, S. hissarica and S. betoniciflora, respectively. Octadecanal (9.37%) was the most predominant in S. betoniciflora. However, n-butyl octadecenoate (4.92%) was the major volatile in S. byzantina. Benzaldehyde (5.01%) was present at a higher percentage in S. hissarica. A chemometric analysis revealed the ability of volatile profiling to discriminate between the studied Stachys species. The principal component analysis plot displayed a clear diversity of Stachys species where the octadecanal and benzaldehyde were the main discriminating markers. The antioxidant activity was evaluated in vitro using 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2-azino bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing power (FRAP), chelating and phosphomolybdenum (PBD). Moreover, the ability of the essential oils to inhibit both acetyl/butyrylcholinesterases (AChE and BChE), α-amylase, α-glucosidase and tyrosinase was assessed. The volatiles from S. hissarica exhibited the highest activity in both the ABTS (226.48 ± 1.75 mg Trolox equivalent (TE)/g oil) and FRAP (109.55 ± 3.24 mg TE/g oil) assays. However, S. betoniciflora displayed the strongest activity in the other assays (174.94 ± 0.20 mg TE/g oil for CUPRAC, 60.11 ± 0.36 mg EDTA equivalent (EDTAE)/g oil for chelating and 28.24 ± 1.00 (mmol TE/g oil) for PBD. Regarding the enzyme inhibitory activity, S. byzantina demonstrated the strongest AChE (5.64 ± 0.04 mg galantamine equivalent (GALAE)/g oil) and tyrosinase inhibitory (101.07 ± 0.60 mg kojic acid equivalent (KAE)/g) activity. The highest activity for BChE (11.18 ± 0.19 mg GALAE/g oil), amylase inhibition (0.76 ± 0.02 mmol acarbose equivalent (ACAE)/g oil) and glucosidase inhibition (24.11 ± 0.06 mmol ACAE/g oil) was observed in S. betoniciflora. These results showed that EOs of Stachys species could be used as antioxidant, hypoglycemic and skincare agents.

Unprecedented Insights on Chemical and Biological Significance of Euphorbia cactus Growing in Saudi Arabia.

Euphorbia cactus Ehrenb ex Boiss. is a plant species reported from central Africa and the southern Arabian Peninsula, belonging to the family of Euphorbiaceae. The plant has ethnobotanical values and is well-known for its milky latex, which has been turned into medicine to treat various ailments. To the best of our knowledge, there have been no literature reports available on phytochemical constituents and antiproliferative mechanism of E. cactus. In the current study, the phytochemical investigation of E. cactus methanolic extract (ECME) resulted in the isolation and characterization of four secondary metabolites, which are reported for the first time from this plant species. In addition, the results of 1,1-diphenyl-2-picrylhydrazyl (DPPH•) and ferrous ion chelating (FIC) assays expressed maximum antioxidant activity by ECME and the isolated phytochemicals. Furthermore, ECME exerted a promising antiproliferative effect against different cancer cell lines, and the A549 lung cancer cells were the most sensitive with an IC50 value of 20 µg/mL. The antiproliferative action of ECME in A549 cells was associated with cell accumulation in the G2/M phase and an increase in early and late apoptosis. In addition, RT-PCR and western blot analysis revealed that ECME decreased the anti-apoptotic (Bcl-2) expression, while the expression of pro-apoptotic (Bax) and caspase-3 were increased. This study provides the first insight into the phytochemical constituents and the antiproliferative mechanism of ECME, implying that it could be exploited as a promising natural source for developing new cancer therapies. Further preclinical research is warranted to support the current results.

HR-LC-ESI-Orbitrap-MS-Based Metabolic Profiling Coupled with Chemometrics for the Discrimination of Different Echinops spinosus Organs and Evaluation of Their Antioxidant Activity.

This study aimed to assess and correlate the phenolic content and the antioxidant activity of the methanol extracts of the stems, roots, flowers, and leaves of Echinops spinosus L. from north-eastern Algeria. Qualitative analysis was performed by high-resolution mass spectrometry (HR) LC-ESI-Orbitrap-MS and (HR) LC-ESI-Orbitrap-MS/MS). Forty-five compounds were identified in the methanol extracts; some are described for the first time in E. spinosus. Targeted phenolic compounds were quantified by HPLC-DAD and it was shown that caffeoyl quinic derivatives were the most abundant compounds. Chemometric analysis was performed using principal component analysis (PCA) and hierarchical cluster analysis (HCA) based on the qualitative and quantitative LC data. The score plot discriminates different Echinopsis spinosus organs into three distinct clusters, with the stems and flowers allocated in the same cluster, reflecting their resemblance in their secondary metabolites. The antioxidant activities of the methanol extracts were assessed using cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant assay (FRAP), diphenyl picryl hydrazyl radical-scavenging capacity assay (DPPH●), and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS●+). The root extract exhibited the highest antioxidant activity, evidenced by 3.26 and 1.61 mmol Fe2+/g dried residue for CUPRAC and FRAP, respectively, and great free radical-scavenging activities estimated by 0.53 and 0.82 mmol TEAC/g dried residue for DPPH● and ABTS●+, respectively. The methanol extract of the roots demonstrated a significant level of total phenolics (TP: 125.16 mg GAE/g dried residue) and flavonoids (TFI: 25.40 QE/g dried residue TFII: 140 CE/g dried residue). Molecular docking revealed that tricaffeoyl-altraric acid and dicaffeoyl-altraric acid exhibited the best fit within the active sites of NADPH oxidase (NO) and myeloperoxidase (MP). From ADME/TOPAKT analyses, it can be concluded that tricaffeoyl-altraric acid and dicaffeoyl-altraric acid also revealed reasonable pharmacokinetic and pharmacodynamic characteristics with a significant safety profile.

Abubidentin A, New Oleanane-type Triterpene Ester from Abutilon bidentatum and its antioxidant, cholinesterase and antimicrobial activities.

Background: This work describes the phytochemical and biological investigation of aerial parts of Abutilon bidentatum Hochst. Of Saudi origin. Methodology: Petroleum ether fraction of ethanolic extract A. bidentatum was fractionated on a silica gel column and further purified with different chromatographic procedures for the isolation of chemical compounds. The chemical structures of all the pure isolated compounds were elucidated by the interpretation of their spectral data using IR, UV, 1H, 13C NMR, and MS spectroscopy and chemical methods (alkaline hydrolysis) as well as comparison with data reported in the literature. The extract and isolated compounds were evaluated for antioxidant, cholinesterase inhibitory, and antimicrobial activities. Results: A new oleanane-type triterpene ester, namely abubidentin A (3) (α, 3ß, 30-trihydroxy-29-carboxy-olean-9(11), 12-diene-3-dotriacontanoate), along with two known compounds: 2-hydroxydocosanoic acid (1) and stigmasta-22-ene-3-ß-ol (2) were isolated from the aerial parts of Abutilon bidentatum Hochst. (Malvaceae). Concerning the biological potential, the abubidentinA displayed antioxidant, cholinesterase inhibitory and antimicrobial activities. AbubidentinA possessed strong antioxidant activity against DPPH and ABTS+ radical scavenging assays. This new triterpene exhibited high inhibition against acetylcholinesterase (IC50 38.13 ± 0.07 µgmL-1) and butyrylcholinesterase (IC50 32.68 ± 0.37 µgmL-1). Abubidentin A displayed promising antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus (125-150 µgmL-1). Conclusion: These findings suggest A. bidentatum can contribute as a source of new biologically active compounds, especially antioxidants and antimicrobial agents.

The Fluorescence Detection of Phenolic Compounds in Plicosepalus curviflorus Extract Using Biosynthesized ZnO Nanoparticles and Their Biomedical Potential.

A facile, eco-friendly fluorescence approach based on the biogenic formation of zinc oxide nanoparticles using the biomass of Plicosepalus curviflorus shoots was developed. The suggested approach was employed to analyze three phenolic compounds (catechin, curviflorside, and curviflorin) isolated from the shoots of P. curviflorus. The surface morphology of the prepared ZnONPs was characterized by carrying out different microscopic and spectroscopic investigations. A significant UV-Vis absorption peak of ZnONPs was recognized at 345 nm and the FT-IR spectra of the isolated catechin, curviflorside, and curviflorin in the presence of sodium dodecyl sulfate (SDS) and ZnONPs were recorded at λem 470, 490, and 484 nm after excitation at λex 380, 420, and 410 nm. The suggested fluorescence method displayed linear concentration ranges of 10-120, 5-100, and 10-150 µg mL-1 for the three isolated compounds, respectively. The shoot extract, isolated compounds, and ZnONPs were screened for antibacterial and anticancer effects against four different types of bacterial strains and HeLa cells, respectively. The ZnONPs exhibited the highest zone of inhibition against Escherichia coli and Staphylococcus aureus strains when compared with pure, isolated compounds and shoot extract. The anticancer potential of ZnONPs (64%) was stronger as compared to the 160 µg mL-1 of shoot extract (49%), catechin (52%), curviflorside (54%), and curviflorin (58%) at 160 µg mL-1. Moreover, all the samples were investigated for hemolysis activity and showed a potent anti-hemolytic effect. The developed analytical method showed excellent sensitivity and reliability for the concurrent analysis of the isolated bioactive markers.

Immunomodulatory and Antiprotozoal Potential of Fabricated Sesamum radiatum Oil/Polyvinylpyrrolidone/Au Polymeric Bionanocomposite Film.

A unique morphological Sesamum radiatum oil/polyvinylpyrrolidone/gold polymeric bionanocomposite film was synthesized using the S. radiatum oil dispersed in a polymeric polyvinylpyrrolidone (PVP) matrix and decorated with gold nanoparticles (AuNPs). The chemical and physical characteristics as well as the thermal stability of the synthesized bionanocomposite film were investigated using various spectroscopic and microscopic techniques. The microscopic analysis confirmed well dispersed AuNPs in the PVP- S. radiatum oil matrix with particle size of 100 nm. Immunomodulatory and antiprotozoal potentials of the suggested bionanocomposite film were evaluated for lipopolysaccharide-induced BV-2 microglia and against L. amazonensis, L. mexicana promastigotes and T. cruzi epimastigotes, respectively. The results exerted outstanding reduction of inflammatory cytokines' (IL-6 and TNFα) secretions after pretreatment of bionanocomposite. The bionanocomposite exhibited large inhibitory effects on certain cell signaling components that are related to the activation of expression of proinflammatory cytokines. Additionally, AuNPs and bionanocomposite exhibited excellent growth inhibition of L. mexicana and L. amazonensis promastigotes with IC50 (1.71 ± 1.49, 1.68 ± 0.75) and (1.12 ± 1.10, 1.42 ± 0.69), respectively. However, the nanomaterials showed moderate activity towards T. cruzi. All outcomes indicated promising immunomodulatory, antiprotozoal, and photocatalytic potentials for the synthesized S. radiatum oil/PVP/Au polymeric bionanocomposite.

Immunomodulatory and Antioxidant Potential of Biogenic Functionalized Polymeric Nutmeg Oil/Polyurethane/ZnO Bionanocomposite.

The current study is focused on the biosynthesis of nutmeg oil/ polyurethane/ZnONPs bionanocomposite film for immunomodulatory and antioxidant activities. The fabricated film was prepared by using naturally extracted nutmeg oil functionalized with ZnONPs in the presence of polyutherane (PU) medium. The bionanocomposite film was obtained by incorporating dropwise 10 % (w/v) of nutmeg oil to the PU solution/ZnONPs blend. The active constituents of nutmeg oil were determined by gas chromatography coupled with mass spectrometry (GC-MS). The morphological characteristics of the resulting bionanocomposite film were confirmed using various microscopic and spectroscopic methods. Immunomodulatory potential of bionanocomposite was evaluated for RAW 264.7 macrophages. The results exhibited an excellent reduction in inflammatory cytokines (IL-6, IL-10, and TNFα) secretions after the treatment with bionanocomposite. The bionanocomposite exerted the highest inhibitory effects on certain cell signaling constituents that influence the initiation of expression of proinflammatory cytokines. The bionanocomposite was also tested for DPPH and ABTS free radicals scavenging assays and showed excellent antioxidant potential with IC50 values (0.28 ± 0.22 and 0.49 ± 0.36), respectively. The outcomes suggested promising immunomodulatory and antioxidant potentials for the biogenic synthesized nutmeg oil/PU/ZnONPs polymeric bionanocomposite.

Antibacterial and Anticancer Potentials of Presynthesized Photosensitive Plectranthus cylindraceus Oil/TiO2/Polyethylene Glycol Polymeric Bionanocomposite.

The present study is concerned with the fabrication of the bifunctional Plectranthus cylindraceus oil/TiO2/polyethylene glycol polymeric film for antibacterial and anticancer activities. The suggested film is based on the utility of naturally extracted P. cylindraceus oil in the formation of the polymeric bionanocomposite film decorated with TiO2 nanoparticles. The bionanocomposite film was fabricated by incorporating 15 w% of P. cylindraceus oil with 10 w% polyethylene glycol and 5 w% TiO2 nanoparticles. The active components of P. cylindraceus oil were verified using gas chromatography coupled with mass spectrometry (GC-MS). The surface morphology of the resulted bionanocomposite film was characterized by various spectroscopic and microscopic techniques. The antibacterial potential of the fabricated bionanocomposite film was investigated against four pathogenic strains. The obtained results revealed excellent sensitivity against the bacterial strains, particularly E. coli and S. aureus, with minimum inhibitory concentration 320 µg mL-1 and minimum bactericidal concentration 640 and 1280 µg mL-1 for E. coli and S. aureus, respectively. Polymeric bionanocomposite exerted significant cytotoxicity against human lung carcinoma cell lines in a concentration-dependent manner with an IC50 value of 42.7 ± 0.25 µg mL-1. Safety assessment test against peripheral blood mononuclear cells (PBMCs) demonstrated that the bionanocomposite is nontoxic in nature. Bionanocomposite also showed potent photocatalytic effects. Overall, the results concluded that the bionanocomposite has expressed scope for multifaceted biomedical applications.

Validation of the Antioxidant and Enzyme Inhibitory Potential of Selected Triterpenes Using In Vitro and In Silico Studies, and the Evaluation of Their ADMET Properties.

The antioxidant and enzyme inhibitory potential of fifteen cycloartane-type triterpenes' potentials were investigated using different assays. In the phosphomolybdenum method, cycloalpioside D (6) (4.05 mmol TEs/g) showed the highest activity. In 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical and 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) cation radical scavenging assays, cycloorbicoside A-7-monoacetate (2) (5.03 mg TE/g) and cycloorbicoside B (10) (10.60 mg TE/g) displayed the highest activities, respectively. Oleanolic acid (14) (51.45 mg TE/g) and 3-O-ß-d-xylopyranoside-(23R,24S)-16ß,23;16α,24-diepoxycycloart-25(26)-en-3ß,7ß-diol 7-monoacetate (4) (13.25 mg TE/g) revealed the highest reducing power in cupric ion-reducing activity (CUPRAC) and ferric-reducing antioxidant power (FRAP) assays, respectively. In metal-chelating activity on ferrous ions, compound 2 displayed the highest activity estimated by 41.00 mg EDTAE/g (EDTA equivalents/g). The tested triterpenes showed promising AChE and BChE inhibitory potential with 3-O-ß-d-xylopyranoside-(23R,24S)-16ß,23;16α,24-diepoxycycloart-25(26)-en-3ß,7ß-diol 2',3',4',7-tetraacetate (3), exhibiting the highest inhibitory activity as estimated from 5.64 and 5.19 mg GALAE/g (galantamine equivalent/g), respectively. Compound 2 displayed the most potent tyrosinase inhibitory activity (113.24 mg KAE/g (mg kojic acid equivalent/g)). Regarding α-amylase and α-glucosidase inhibition, 3-O-ß-d-xylopyranoside-(23R,24S)-16ß,23;16α,24-diepoxycycloart-25(26)-en-3ß,7ß-diol (5) (0.55 mmol ACAE/g) and compound 3 (25.18 mmol ACAE/g) exerted the highest activities, respectively. In silico studies focused on compounds 2, 6, and 7 as inhibitors of tyrosinase revealed that compound 2 displayed a good ranking score (-7.069 kcal/mole) and also that the ΔG free-binding energy was the highest among the three selected compounds. From the ADMET/TOPKAT prediction, it can be concluded that compounds 4 and 5 displayed the best pharmacokinetic and pharmacodynamic behavior, with considerable activity in most of the examined assays.

Morphology, Anatomy and Secondary Metabolites Investigations of Premna odorata Blanco and Evaluation of Its Anti-Tuberculosis Activity Using In Vitro and In Silico Studies.

In-depth botanical characterization was performed on Premna odorata Blanco (Lamiaceae) different organs for the first time. The leaves are opposite, hairy and green in color. Flowers possess fragrant aromatic odors and exist in inflorescences of 4-15 cm long corymbose cyme-type. In-depth morphological and anatomical characterization revealed the great resemblance to plants of the genus Premna and of the family Lamiaceae, such as the presence of glandular peltate trichomes and diacytic stomata. Additionally, most examined organs are characterized by non-glandular multicellular covering trichomes, acicular, and rhombic calcium oxalate crystals. P. odorata leaves n-hexane fraction revealed substantial anti-tuberculous potential versus Mycobacterium tuberculosis, showing a minimum inhibition concentration (MIC) of 100 µg/mL. Metabolic profiling of the n-hexane fraction using gas-chromatography coupled to mass spectrometry (GC/MS) analysis revealed 10 major compounds accounting for 93.01%, with trans-phytol constituting the major compound (24.06%). The virtual screening revealed that trans-phytol highly inhibited MTB C171Q receptor as M. tuberculosis KasA (ß-ketoacyl synthases) with a high fitting score (∆G = -15.57 kcal/mol) approaching that of isoniazid and exceeding that of thiolactomycin, the co-crystallized ligand. Absorption, distribution, metabolism, excretion and toxicity predictions (ADME/TOPKAT) revealed that trans-phytol shows lower solubility and absorption levels when compared to thiolactomycin and isoniazid. Still, it is safer, causing no mutagenic or carcinogenic effects with higher lethal dose, which causes the death of 50% (LD50). Thus, it can be concluded that P. odorata can act as a source of lead entities to treat tuberculosis.

Discrimination of the Essential Oils Obtained from Four Apiaceae Species Using Multivariate Analysis Based on the Chemical Compositions and Their Biological Activity.

The chemical composition of the essential oils obtained from the aerial parts of four Apiaceae species, namely Elaeosticta allioides (EA), E. polycarpa (EP), Ferula clematidifolia (FC), and Hyalolaena intermedia (HI), were determined using gas chromatography. Altogether, 100 volatile metabolites representing 78.97, 81.03, 85.78, and 84.49% of the total components present in EA, EP, FC, and HI oils, respectively, were reported. allo-Ocimene (14.55%) was the major component in FC, followed by D-limonene (9.42%). However, in EA, germacrene D (16.09%) was present in a high amount, while heptanal (36.89%) was the predominant compound in HI. The gas chromatographic data were subjected to principal component analysis (PCA) to explore the correlations between these species. Fortunately, the PCA score plot could differentiate between the species and correlate Ferula to Elaeosticta species. Additionally, the antioxidant activity was evaluated in vitro using the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and the ferric reducing power (FRAP) assays. In addition, the antimicrobial activity using the agar diffusion method was assessed, and the minimum inhibitory concentrations (MICs) were determined. Furthermore, the cell viability MTT assay was performed to evaluate the cytotoxicity of the essential oils against hepatic (HepG-2) and cervical (HeLa) cancer cell lines. In the DPPH assay, FC exhibited the maximum activity against all the antioxidant assays with IC50 values of 19.8 and 23.0 µg/mL for the DPPH and ABTS assays, respectively. Ferula showed superior antimicrobial and cytotoxic activities as well. Finally, a partial least square regression model was constructed to predict the antioxidant capacity by utilizing the metabolite profiling data. The model showed excellent predictive ability by applying the ABTS assay.

The protective effect of Moringa oleifera plant extract against glutamate-induced DNA damage and reduced cell viability in a primary retinal ganglion cell line.

BACKGROUND: Glutamate excitotoxicity can cause DNA damage and is linked to many retinal and neurological disorders. In mammals, the visual signal from the eyes to the brain is conducted only by retinal ganglion cells (RGCs), which can be damaged by overstimulation of glutamate receptors. METHODOLOGY: We examined the protective effects of Moringa oleifera seed extract against glutamate-induced DNA damage in RGCs. RGCs cells were treated with 5, 10, 50, or 100 µg/ml of M. oleifera seed extract and glutamate separately and then assessed for DNA damage using the comet assay. We also evaluated the viability of the RGCs after both treatments using the MTT test. Additionally, RGCs were pretreated with M. oleifera seed extract (50 or 100 µg/ml) for 2 h before glutamate treatment (100 µg/ml) to determine the potential protective effects of M. oleifera. We performed a phytochemical analysis of the M. oleifera seed extract using standard reactions. RESULTS: The M. oleifera seed extract was found to be rich in many phytochemicals. We observed a significant dose-dependent elevation in all comet assay variables in glutamate-treated RGCs, whereas M. oleifera seed extract treatments did not show any significant change in DNA integrity. CONCLUSION: M. oleifera seed extract demonstrates neuroprotective effects, which suggests it may help to prevent the development of many neurodegenerative disorders.

Lepidium sativum as candidate against excitotoxicity in retinal ganglion cells.

Glutamate excitotoxicity is considered one of the major causes of retinal ganglion cell death in many retinal diseases. Retinal ganglion cell degeneration causes severe blindness since visual signals from the eye to the brain are conducted only through retinal ganglion cells. OBJECTIVE: We aimed to explore the potential ameliorative effects of L. sativum against glutamate excitotoxicity-induced retinal ganglion cell damage. METHODS: Pure retinal ganglion cells were divided into a control group (untreated); L. sativum-treated groups in which retinal ganglion cells were treated with 5, 10, 50, or 100 µg/mL L. sativum seed extract for 2 h; glutamate-treated groups in which cells were treated with 5, 10, 50, or 100 µM glutamate for 48 h; and L. sativum/glutamate groups [pretreatment with L. sativum for 2 h (50 or 100 µg/mL) before glutamate treatment at 100 µM for 48 h]. Cell damage was assessed by comet assay and cell viability was by MTT test. RESULTS: Tailed DNA, tail length, and tail moment of the 50 and 100 mM glutamate-treated groups were significantly greater than those of the blank control group, while the L. sativum-treated groups demonstrated nonsignificantly different tailed DNA, tail length, and tail moment compared with the blank control group, but significantly lower values compared with the glutamate-treated groups. CONCLUSION: L. sativum ameliorated the cell viability in retinal ganglion cells after high-concentration glutamate exposure. L. sativum seed extracts were efficient anti-excitotoxic and antioxidant agent that might improve the clinical presentation of many neurological disorders.

Cytotoxic and anti-excitotoxic effects of selected plant and algal extracts using COMET and cell viability assays.

Excess glutamate in the central nervous system may be a major cause of neurodegenerative diseases with gradual loss and dysfunction of neurons. Primary or secondary metabolites from medicinal plants and algae show potential for treatment of glutamate-induced excitotoxicity. Three plant extracts were evaluated for impact on glutamate excitotoxicity-induced in primary cultures of retinal ganglion cells (RGC). These cells were treated separately in seven groups: control; Plicosepalus. curviflorus treated; Saussurea lappa treated; Cladophora glomerate treated. Cells were treated independently with 5, 10, 50, or 100 µg/ml of extracts of plant or alga material, respectively, for 2 h. Glutamate-treated cells (48 h with 5, 10, 50, or 100 µM glutamate); and P. curviflorus/glutamate; S. lappa/glutamate; C. glomerata/glutamate [pretreatment with extract for 2 h (50 and 100 µg/ml) before glutamate treatment with 100 µM for 48 h]. Comet and MTT assays were used to assess cell damage and cell viability. The number of viable cells fell significantly after glutamate exposure. Exposure to plant extracts caused no notable effect of viability. All tested plants extracts showed a protective effect against glutamate excitotoxicity-induced RGC death. Use of these extracts for neurological conditions related to excitotoxicity and oxidative stress might prove beneficial.