NO Free Radical Research Articles

Experimental and theoretical vibrational analysis, structural conformations, DFT estimations, antibacterial, antifungal, DPPH,H2O2, Nitric oxide scavenging activity drug, in silico molecular docking, and ADMET studies of N-(2-carboxylphenyl) phthalimide (CPPD)

The title compound N-(2-carboxylphenyl) phthalimide (CPPD)was purchased with a stated purity of 99 % from M/S. Sigma-Aldrich Co. and utilized as such with no additional purification,CPPD is a thalidomide based derivative, which have led to the uses of most important drugs from 1950 and their mechanisms of action is essential for a better understanding of molecular targets with broad spectrum of biological activity. The obtained FTIR spectral data of the compound were compared to harmonic vibrational frequencies calculated using the ab initio DFT (B3LYP) technique with 6–311++G (d,p)basis sets. Furthermore, 13C and 1H NMR, first-order hyperpolarizability (βo) associated parameters (π, αo)of the compound, theSubsequent to recording the molecule’sUV–Visible spectra, DFT was used to analyze its electronic characteristics, including its HOMO and LUMO energies, molecular electrostatic potential (MESP), and Mulliken population studies were using ab initio DFT6-311++G (d,p)basis sets. Pharmacological Screening investigation of the title molecule showed a strong broad-spectrum of antifungal and antibacterial activity against various Gram (+) and Gram (−) bacteria using Ciprofloxacin as a positive control. The headline molecule is subjected toIn-silico molecular docking research with the purpose of improved recognize its biological activities, in addition with the minimal binding energy and hydrogen bond interaction that can view by Discovery Studio 4.0 visualizers. and drug likeness using Swiss ADME predictor (http://www.swissadme.ch/index.php) along with AdmetSAR-2.0 online software analysis tools features were investigated. The compound CPPD’s ability to degrade DPPH increased as a dose-dependent manner, with its maximal DPPH scavenging characteristic spanning from (18.2 ± 1.5 % to 73.2 ± 1.7 %) and maximum H2O2 scavenging trait ranging from (35.5 ± 5.3to 88.8 ± 3.1 %). The NO free radical scavenging property is linearly dependent on CPPD concentration. The interaction between the CPPD ligands and the 1HD2 protein is demonstrated by these data, as the protein displays a reduced binding energy value of −7.3 (Kcal/mol) and an inhibitory constant (ki) value of 4.39 μM. In swiss ADME prediction, CPPD is an evident from the physicochemical data that has an efficient receptor site binding mechanism. The lipophilicity of a drug is determined by its partition coefficient (Log P=log Po/w) between water and N-(2-carboxylphenyl) phthalimide. The paper further explains that the title compound can act as promising antibacterial and antioxidant agent throughin-vitro and molecular docking studies.

Pyrazole-based N-phenyl pyrazolines: Synthesis, docking, and pharmacological evaluation

A series of methoxy substituted pyrazole based pyrazoline derivatives (4a-j) were synthesized in good to excellent yield from corresponding pyrazole-chalcones (3a-j). All synthesized derivatives were characterized and screened for their in vitro anti-inflammatory, antioxidant, antidiabetic, and antibacterial activities. Among the series, compounds 4f, 4j, 4a, and 4i showed better anti-inflammatory activity as compared to diclofenac sodium. In DPPH free radical scavenging assay, all the compounds were shown excellent activity and moderate to good activity in SO and NO free radical scavenging assay as compared to standard ascorbic acid. Antibacterial screening of synthesized pyrazolines showed that compounds 4f and 4j have significant antibacterial activity. The compounds 4j, 4f, 4h, 4a, and 4c have shown comparable inhibition of alpha-amylase enzyme leading to good antidiabetic activity as compared to standard acarbose. Molecular docking studies suggest that these compounds have strong binding with COX-2 and alpha-amylase enzyme due to significant capability of aromatic and hydrophobic interaction. The outstanding results of reported compounds in all biological screening will pave the way for the design of new drug candidate bearing pyrazole moiety.

Insight into the photodynamic mechanism and protein binding of a nitrosyl iron−sulfur [Fe2S2(NO)4]2− cluster

Iron−sulfur cluster conversion and nitrosyl modification are involved in regulating their functions and play critical roles in signaling for biological systems. Hereby, the photo-induced dynamic process of (Me4N)2[Fe2S2(NO)4] was monitored using time-resolved electron paramagnetic resonance (EPR) spectra, MS spectra and cellular imaging methods. Photo-irradiation and the solvent affect the reaction rates and products. Spectroscopic and kinetic studies have shown that the process involves at least three intermediates: spin-trapped NO free radical species with a gav at 2.040, and two other iron nitrosyl species, dinitrosyl iron units (DNICs) and mononitrosyl iron units (MNICs) with gav values at 2.031 and 2.024, respectively. Moreover, the [Fe2S2(NO)4]2- cluster could bind with ferritin and decompose gradually, and a binding state of dinitrosyl iron coordinated with Cys102 of the recombinant human heavy chain ferritin (rHuHF) was finally formed. This study provides insight into the photodynamic mechanism of nitrosyl iron − sulfur clusters to improve the understanding of physiological activity.

Inflammatory profiles in women with eating disorder: Linking inflammatory biomarkers to clinical phenotypes

IntroductionEating disorders (ED) represent a group of very complex and serious diagnoses characterized by emotional dysregulation and impulsivity. New approaches are necessary to achieve effective diagnosis and treatments. Shifting biomarker research away from the constraints of diagnostic categories may effectively contribute to a dimensional differentiation across disorders according to neurobiology (e.g., inflammatory biomarkers). Thus, the aim of our study was to identify inflammatory profiles in patients with ED. MethodsA sample of 100 women with an ED (23.4 ± 8.55 years) and 59 healthy controls (HC) (20.22 ± 4.18 years) was used. K-means cluster analysis was followed to identify inflammatory clusters considering seven blood biomarkers (iNOS, TNFα, COX2, p38, ERK, TBARS and PPARγ). Moreover, a wide assessment of clinical features was conducted. ResultsTwo distinct clusters were identified. Cluster 1 patients were characterized by higher inflammatory levels of TNF-α, COX2, p38, and ERK, and had more restrictive anorexia diagnosis than cluster 2. Cluster 2 participants showed higher inflammatory levels of iNOS and were older than cluster 1 and controls and had lower BMI than HC. In addition, they had higher levels of bulimic symptoms than those from the cluster 1 and HC, and higher impulsivity than HC. All ED patients (regardless of cluster) showed higher ED symptoms and more trauma than HC. ConclusionsOur study revealed that inflammatory dysfunction may be linked with clinical endophenotypes in ED, one more restrictive (cluster 1) with an inflammation/oxidative endophenotype more cytokine and MAPK/ERK mediated, and the other more impulsive, with more bulimic symptoms (cluster 2) with NO free radical high output source iNOS. Trauma seems to be a vulnerability factor for both endophenotypes.

Polyphenol Mediated Suppression of Hepatocellular Carcinoma (HepG2) Cell Proliferation by Clerodendrum infortunatum L. Root.

Clerodendrum infortunatum L. has long been used in traditional medicine in Sri Lanka for tumours, cancer, and certain skin diseases. The present study aimed to assess the anticancer properties of the aqueous extract of C. infortunatum L. root (AECIR) through the activation of the apoptotic pathway on hepatocellular carcinoma (HepG2) and thus give it a scientific validation. Further, the contribution of polyphenols in antioxidant activity and cell cytotoxicity was investigated. Powdered plant material was boiled with water (100°C) to obtained AECIR. The DPPH assay was used to determine the antioxidant potential. The activity of AECIR on HepG2 and normal rat fibroblast (CC1) cell growth was determined using MTT assay. The morphological changes related to apoptotic pathway was examined by Ethidium Bromide/Acridine Orange (EB/AO), Rhodamine 123 (Rh123) and DNA fragmentation assay. The AECIR demonstrated antioxidant potential with an EC50 of 350.2 ± 1.5 ug/mL for DPPH assay. The HO•, H2O2 and •NO free radical scavenging activity was observed with EC50 of 19.7 ± 2.3, 11.7 ± 0.1 and 273.1 ± 0.9 ug/mL, respectively. The antiproliferative effect of AECIR on HepG2 cells was observed in a time and dose dependent manner with an EC50 of 239.1 ± 1.3 μg/mL while CC1 cells showed a nontoxic effect with an EC50 1062.7 ± 3.4 μg/mL after 24hrs treatment. A significant decrease in antioxidant activity (p<0.001) and 90% HepG2 cell viability was observed with polyphenol removed AECIR compared to the polyphenol present AECIR. The EB/AO uptake, depletion of mitochondrial transmembrane potential, and DNA fragmentation assay results revealed that the apoptosis was induced by AECIR. The obtained result of the present study demonstrates that the antioxidant potential and antiproliferative activity of AECIR is attributed to the presence of polyphenols. Furthermore, the findings provide the scientific base for anti-cancer potential of AECIR.

Theoretical study on the inherent relationship between laminar burning velocity, ignition delay time, and NO emission of ammonia-syngas-air mixtures under gas turbine conditions

This study utilizes numerical methods with Chemkin 19.2 and Matlab R2020a to investigate the relationship between laminar burning velocity and free radical concentration, the relationship between laminar burning velocity and ignition delay time, and the relationship between NO emissions and free radical concentration for ammonia-syngas-air combustion. Additionally, it explores the mechanisms by which these three relationships change with variations in the initiate temperature and chamber pressure of the combustion chamber. Furthermore, to understand the theoretical foundation of these relationships, the study examines four global flame parameters: adiabatic flame temperature (Tad), activation energy (Ea), Zeldovich number (Ze), and Lewis number (Le). The results indicate that changes in initial temperature and pressure influence the laminar burning velocity by modifying the concentration of H + NH2 radicals. Simultaneously, alterations in initial temperature and pressure also adjust the quantitative relationship between laminar burning velocity and the concentration of H + NH2 radicals. Additionally, the results reveal that variations in initial temperature and pressure impact NO emissions by altering the concentration of H + NH2 radicals. Following a comprehensive examination of both the theoretical relationship between laminar burning velocity and ignition delay time and the empirical relationship between laminar burning velocity and ignition delay time, a relationship between the density-weighted collision rate BC in the laminar burning velocity expression and the pre-exponential factor A in the theoretical expression for ignition delay time was observed, where BC2A = C0∙Tuδ∙Pε (where C0, δ and ε are constants). This offers a potential methodology for investigating thermal effects, chemical effects, and transport effects in complex mixed fuel combustion processes. Further investigation demonstrates that an increase in the initial temperature within a gas turbine combustion chamber will, by promoting thermal effects, inhibiting transport effects, and altering chemical effects, affect the quantitative relationship between laminar burning velocity and ignition delay time. Further research reveals that an increase in the initiate temperature of the gas turbine combustion chamber affects the quantitative relationships between laminar burning velocity and ignition delay time by promoting thermal effects, suppressing transport effects, and chemical effects. An increase in chamber pressure influences these relationships by enhancing chemical and transport effects while inhibiting thermal effects. Moreover, the functions characterizing chemical effects, transport effects, and thermal effects can be reasonably approximated in this study as functions of initial temperature and pressure, especially under the specific F-class gas turbine conditions presented herein. This finding holds significance for the design of combustion chambers under actual gas turbine operating conditions.

A brief report on eugenol oleate is an oral immunomodulatory molecule against visceral leishmaniasis

Visceral Leishmaniasis (VL) is a life-threatening infectious disease and is acclaimed as a neglected tropical disease, caused by Leishmania donovani. It leads to severe immune suppression in the host defense system. Higher cytotoxicity, rigorous side effects, and lower therapeutic indexes (TI) of current antileishmanial drugs have created a necessity to develop new molecules with better antileishmanial activity and high TI value. We synthesized a plenty number of derivatives of Eugenol and screened them for their activity against promastigote and amastigote forms of L. donovani. Among the synthesized derivatives, Eugenol oleate showed better antileishmanial activity against extracellular promastigotes (IC50- 20.13 ± 0.91 μM) and intracellular amastigotes (EC50-4.25 ± 0.26 μM). The TI value (82.24 ± 3.77) was found to improve by 10 to 13-folds compared to amphotericin B and miltefosine, respectively. Treatment with Eugenol oleate activated the PKC-βII–p38 MAPK and produced IL-12 and IFN-γ, which activated the iNOS2 to produce NO free radicals that cleared the intracellular parasite. Eugenol oleate was found safe with an appreciable pharmacokinetic profile for the oral anti-VL agent. This molecule increased the Th1 cytokine profile and decreased the Th2 cytokine profile observed from ELISA and qPCR, suggesting that the Eugenol oleate induced the parasite clearance through the activation of the host immune system. Hence, this study represented that Eugenol oleate, an oral immunomodulatory molecule, could induce a host protective immune response against visceral leishmaniasis through enhanced NO generation and Th1 response, essential against this deadly disease.

Antioxidant activity of Loranthus ferrugineus twigs extracts

Background: A coffee parasite, Loranthus ferrugineus, is a type of parasitic plant that is widely used as a medicinal plant. It has many activities, including as an antioxidant agent. Objective: This study is to determine the antioxidant activity in the twig extracts of L. ferrugineus. Method: The twigs of L. ferrugineus were collected from Pekanbaru, Riau Province, Indonesia. Extraction was carried out by maceration of the dry twigs using methanol, and then liquid-liquid extraction was carried out to obtain ethyl acetate and methanol fractions. The antioxidant activity test was carried out using the radical DPPH and NO free radical scavenging methods by calculating the IC50 values, and the total phenolic content (TPC) was measured. Result: The antioxidant activity assay of the DPPH method on ethyl acetate and methanol extracts revealed IC50 values of 20.85 µg/mL and 18.83 µg/mL, respectively. Meanwhile, the NO free radical method on ethyl acetate and methanol extracts showed IC50 values of 78.52 µg/mL and greater than 1000 µg/mL. The total phenolic content of the ethyl acetate extract was 26.78 mgGAE/gram, while it was 24.85 mgGAE/gram in the methanol extract. Conclusion: The ethyl acetate and methanol extracts could inhibit free radicals from DPPH, which was classified as very strong antioxidant sources. Meanwhile, the inhibition of the extracts against the NO free radical was very weak.

Dendritic Plasmonic CuPt Alloys for Closed-Loop Multimode Cancer Therapy with Remarkably Enhanced Efficacy.

The outcome of laser-triggered plasmons-induced phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is significantly limited by the hypoxic tumor microenvironment and the upregulation of heat shock proteins (HSPs) in response to heat stress. Mitochondria, the biological battery of cells, can serve as an important breakthrough to overcome these obstacles. Herein, dendritic triangular pyramidal plasmonic CuPt alloys loaded with heat-sensitive NO donor N, N'-di-sec-butyl-N, N'-dinitroso-1,4-phenylenediamine (BNN) is developed. Under 808nm laser irradiation, plasmonic CuPt can generate superoxide anion free radicals (·O2 - ) and heat simultaneously. The heat generated can then trigger the release of NO gas, which not only enables gas therapy but also damages the mitochondrial respiratory chain. Impaired mitochondrial respiration leads to reduced oxygen consumption and insufficient intracellular ATP supply, which effectively alleviates tumor hypoxia and undermines the synthesis of HSPs, in turn boosting plasmonic CuPt-based PDT and mild PTT. Additionally, the generated NO and ·O2 - can react to form more cytotoxic peroxynitrite (ONOO- ). This work describes aplasmonic CuPt@BNN (CPB) triggered closed-loop NO gas, free radicals, and mild photothermal therapy strategy that is highly effective at reciprocally promoting antitumor outcomes.

An Integrated Analysis of Mechanistic Insights into Biomolecular Interactions and Molecular Dynamics of Bio-Inspired Cu(II) and Zn(II) Complexes towards DNA/BSA/SARS-CoV-2 3CLpro by Molecular Docking-Based Virtual Screening and FRET Detection.

Novel constructed bioactive mixed-ligand complexes (1b) [CuII(L)2(phen)] and (2b) [ZnII(L)2(phen)] {where, L = 2-(4-morpholinobenzylideneamino)phenol), phen = 1,10-phenanthroline} have been structurally analysed by various analytical and spectroscopic techniques, including, magnetic moments, thermogravimetric analysis, and X-ray crystallography. Various analytical and spectral measurements assigned showed that all complexes appear to have an octahedral geometry. Agar gel electrophoresis's output demonstrated that the Cu(II) complex (1b) had efficient deoxyribonucleic cleavage and complex (2b) demonstrated the partial cleavage accomplished with an oxidation agent, which generates spreadable OH● through the Fenton type mechanism. The DNA binding constants observed from viscosity, UV-Vis spectral, fluorometric, and electrochemical titrations were in the following sequence: (1b) &gt; (2b) &gt; (HL), which suggests that the complexes (1b-2b) might intercalate DNA, a possibility that is supported by the biothermodynamic measurements. In addition, the observed binding constant results of BSA by electronic absorption and fluorometric titrations indicate that complex (1b) revealed the best binding efficacy as compared to complex (2b) and free ligand. Interestingly, all compounds are found to interact with BSA through a static approach, as further attested by FRET detection. The DFT and molecular docking calculations were also performed to realize the electronic structure, reactivity, and binding capability of all test samples with CT-DNA, BSA, and the SARS-CoV-2 3CLPro, which revealed the binding energies were in a range of -8.1 to -8.9, -7.5 to -10.5 and -6.7--8.8 kcal/mol, respectively. The higher reactivity of the complexes than the free ligand is supported by the FMO theory. Among all the observed data for antioxidant properties against DPPH᛫, ᛫OH, O2-• and NO᛫ free radicals, complex (1a) had the best biological efficacy. The antimicrobial and cytotoxic characteristics of all test compounds have been studied by screening against certain selected microorganisms as well as against A549, HepG2, MCF-7, and NHDF cell lines, respectively. The observed findings revealed that the activity enhances coordination as compared to free ligand via Overtone's and Tweedy's chelation mechanisms. This is especially encouraging given that in every case, the experimental findings and theoretical detections were in perfect accord.

Metals-triggered compound CDPDP exhibits anti-arthritic behavior by downregulating the inflammatory cytokines, and modulating the oxidative storm in mice models with extensive ADMET, docking and simulation studies.

Triggering through abiotic stress, including chemical triggers like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metal Nickel on actinobacteria Streptomyces sp. SH-1327 to obtain a stress-derived compound was firstly investigated. A new compound cyclo-(D)-Pro-(D)-Phe (CDPDP) was triggered from the actinobacteria strain SH-1327 with the addition of nickel ions 1mM. The stress compound was further evaluated for its anti-oxidant, analgesic, and anti-inflammatory activity against rheumatoid arthritis through in-vitro and in-vivo assays in albino mice. A remarkable in-vitro anti-oxidant potential of CDPDP was recorded with the IC50 value of 30.06 ± 5.11μg/ml in DPPH, IC50 of 18.98 ± 2.91 against NO free radicals, the IC50 value of 27.15 ± 3.12 against scavenging ability and IC50 value of 28.40 ± 3.14μg/ml for iron chelation capacity. Downregulation of pro-inflammatory mediators (NO and MDA), suppressed levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-Iβ) and upregulation of expressions of anti-oxidant enzymes (GSH, catalase, and GST) unveiled its anti-inflammatory potential. CDPDP was analyzed in human chondrocyte cell line CHON-001 and the results demonstrated that CDPDP significantly increased cell survival, and inhibited apoptosis of IL-1β treated chondrocytes and IL-1β induced matrix degrading markers. In addition, to evaluate the mitochondrial fitness of CHON-001 cells, CDPDP significantly upregulated pgc1-α, the master regulator of mitochondrial biogenesis, indicating that CDPDP provides protective effects in CHON-001 cells. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile of the CDPDP showed that CDPDP is safe in cases of hepatotoxicity, cardiotoxicity, and cytochrome inhibition. Furthermore, docking results showed good binding of CDPDP with IL-6-17.4kcal/mol, and the simulation studies proved the stability between ligand and protein. Therefore, the findings of the current study prospect CDPDP as a potent anti-oxidant and a plausible anti-arthritic agent with a strong pharmacokinetic and pharmacological profile.

Antioxidant and Cytotoxic Activities of Fractions of Ethanol Leaf Extract of Byrsocarpus Coccineus Schum. and Thonn. (Connaraceae)

Medicinal plants have historically been used traditionally for their therapeutic potentials, they are therefore investigated with the hope of developing novel drugs. This study is to investigate the phytochemicals, antioxidant and cytotoxic activities of Byrsocarpus coccineus fractions. The ethanol leaf extract of B. coccineus was chromatographed on VLC over silica gel (Mesh 70-230) using&nbsp; n-hexane/EtOAc/MeOH eluent system; n-hexane/EtOAc (from100/0 to 0/100), then ethyl acetate (EtOAc)/MeOH (from 100/0 to 0/100) to yield seven (7) fractions.(F1-F7). The phytochemical screening and antioxidant activities of the different fractions were carried out. All the fractions were subjected to gas chromatography and mass spectrometry (GC-MS) analysis and cytotoxic activities of the different fractions were investigated using brine shrimp lethality assay. The phytochemical result showed that fractions contain tannins, flavonoids, phenols, reducing sugar, alkaloids, steroids, saponin and terpenoid. Antioxidant analysis show that F3 had the highest DPPH (IC50=56.88µg/ml) and NO (IC50=53.02µg/ml) free radical scavenging activities. F7 (IC50=56.25 µg/ml) and F3 (IC50 of 56.79 µg/ml), had the highest lipid peroxidation free radical scavenging activity. The brine shrimp toxicity assay result showed that F3 and F4 were cytotoxic to Artemia salina with a LD50 value of 39.01μg/ml and 53.55 μg/ml respectively. The GC-MS analysis showed the presence in the most active fraction with antioxidant (cis-vaccenic acid, neophytadiene), antitumor and cancer preventive (squalene) and anticancer (9-Octadecenoic acid, 9, 12-Octadecadienoic acid, methyl ester) potentials. This study reveals that B. Coccineus contains pharmacologically bioactive compounds with therapeutic potentials. &nbsp;

Antioxidant and antihypertensive potential of Ledebouria hyderabadensis

Ledebouria hyderabadensis is a new species found in the city limits of Hyderabad, Telangana, India, in 2012. Ethanolic extract of L. hyderabadensis bulbs was measured for its antioxidant and antihypertensive. Phytochemical investigation revealed that the plant contains glycosides, saponins, flavonoids, tannins, carbohydrates, amino acids. Acute toxicity studies performed according to OECD 423 guidelines, where a single dose of 5, 50, 300 and 1000 mg/kg of ethanolic extract of L. hyderabadensis bulbs administered to rats did not displayed any toxic symptoms. Therefore 1000 mg/kg is chosen as the therapeutic dose. The ethanolic extract of L. hyderabadensis bulbs exhibited the DPPH and NO free radical scavenging activity in dose dependent manner than ascorbic acid with IC50 value 54.08 µg/ml and 64.67 µg/ml. The L. hyderabadensis extract exhibited statistically significant (p &lt; 0.05) ACE enzyme inhibition IC50 values (59.64µg/ml) when compared to the standard Captopril (IC50=24.67µg/ml). DOCA salt treatment at the 100 mg/kg, and 200 mg/kg doses, significantly reduced the Mean Systolic Blood Pressure (MSBP) (198.8&amp;169.4) compared with the standard Nifedipine (132.6) and the negative control (122.6).

Optimization of alkali extraction, structure, and antioxidant activity of protein-bound polysaccharide from seeds of Plantago ovata Forssk

In this study, the effects of different solvents on the viscosity of the seeds of Plantago ovata Forssk (POF) were compared to select the extraction solvent; then, a three-level and four-variable Box–Behnken design (BBD) was applied to determine the optimum extraction conditions for the maximum yields of polysaccharides from POF. Two novel protein-bound heteropolysaccharides (POFG-1a and POFG-2a) with molecular weights of 118 kDa and 113 kDa were isolated and purified by ethanol fractionation precipitation, DEAE-650 M anion exchange column chromatography, and Sephadex G-100 column chromatography. POFG-1a and POFG-2a contain 49.6% and 17.2% of polysaccharide, 26.9% and 56.4% of protein, 9.1% and 5.0% of uronic acid, respectively; they are rich in monosaccharides, Ara, Gal, and Rha, and amino acids, Ser, Pro, Ile, and Phe. Based on FT-IR, β-elimination, methylation analysis, NMR spectroscopy, and some literature data, it was found that POFG-1a is a homogeneous acidic protein-bound heteropolysaccharide with O-glycosidic linkage. The main chain of POFG-1a is connected by 1→4 Araf and 1→5 Araf with a high degree of branching, connected to the branch at the O-2 and O-3 positions of 1→5 Araf. The POFGs exhibited strong scavenging activity on DPPH, ABTS, and NO free radicals, which is rarely observed in other plant polysaccharides. These results indicate that POFGs might have potential applications in the medical and food industries as novel natural antioxidants.

TOTAL PHENOLIC, FLAVONOID CONTENT, AND ANTIOXIDANT ACTIVITY OF JUSTICIA TRANQUEBARIENSIS L.F. AND CYCAS BEDDOMEI DYER. LEAVES

Polyphenolics such as tannins and flavonoids are proved as powerful antioxidants to resolve cellular stress, sustain homeostasis in the body and prevent stress-associated disorders. Plant-based medicine gained importance due to its safety margin and multiple benefits. Regular intake of antioxidants is an alternative to avoid serious illness. The current investigation is aimed to measure the phenolic, flavonoid content, the antioxidant activity of Justicia tranquebariensis L.f. and Cycas beddomei leaves. The selected plants are used by tribes and traditional medicine to cure various diseases. Total phenolic content was estimated using the Folin–Ciocalteu colorimetric method, taking gallic acid as standard. At the same time, total flavonoid content was determined by aluminum chloride colorimetric assay using Rutin as standard. The absorbance was measured at 760 nm and 510 nm, respectively. Antioxidant activity was measured by two In vitro methods (DPPH and NO free radical scavenging assay) using standard protocols, where Ascorbic acid served as a reference standard. Results disclosed that the total phenolic content for the methanolic extracts of C. beddomei (36.14 ± 1.72) and J. tranquebariensis (28.57 ± 0.91) was found to be higher than petroleum ether extracts. Similarly, C. beddomei (28.13 ± 2.48) is richer in flavonoids than J tranquebariensis (20.32 ± 1.24). In DPPH assay, methanolic extract C. beddomei (78.21%) is more effective to inhibit the free radicals than J. tranquebariensis (73.05%) with IC50 values 41.55μg/ml &amp; 59.52 μg/ml respectively at higher doses that are comparable to standard ascorbic acid (84.34%, IC50 =63.27 μg/ml). Similarly, in NO free radical scavenging assay, methanolic extract of C. beddomei (72.54%) stood best among all to scavenge the free radicals with IC50 values 50.06 μg/ml, whereas ascorbic acid is found to inhibit 83.26% with IC50 values 39.75μg/ml. The presence of various secondary metabolites such as alkaloids, carbohydrates, phenols, steroids, terpenoids, glycosides, saponins, especially tannins and flavonoids, either alone or in combination, may be responsible for the observed scavenging property. The quantity of the phenolic compounds and flavonoids can be directly correlated to the exhibited activity.

Hepatoprotective effect of ferulic acid and/or low doses of γ-irradiation against cisplatin-induced liver injury in rats.

The therapeutic efficacy of cisplatin (CIS) is limited owing to its hepatotoxic side effects. The current study aimed to investigate the protective impact of ferulic acid (FA) and low-doses of γ-irradiation (LDR) against CIS-prompted hepatotoxicity in rats. Adult male Swiss albino rats were divided into eight groups: untreated group; FA, LDR, and CIS treated groups; and combinations of one or more of the above treatments. Post-treatment analyses included measuring redox markers like SOD and CAT activity, NO free radical content, and lipid peroxidation in liver tissue. Serum aminotransferase activities were also determined. Additionally, gene transcript levels of liver NF-ҡB-P65, caspase-1, COX-2, and IL-1β were quantified. Moreover, immunohistochemistry for caspase-3 and histopathological examinations were estimated in liver tissue. Our findings revealed increased levels of oxidative stress along with a significant reduction in anti-oxidative responses and a significant increase in serum aminotransferase activities in the CIS-intoxicated group. A similar increase was also observed in COX-2 and IL-1β transcript levels and caspase-3 enzyme activity, besides a decrease in transcript levels of NF-ҡB-p65 and caspase-1, indicating an overall inflammatory trend and an increase in the apoptotic shift. The co-administration of FA and/or treatment with LDR has ameliorated the hepatotoxic effect induced by CIS. The histopathological investigation of liver tissues confirmed this ameliorating action of these adjuvant therapies against CIS toxicity. In conclusion, it is plausible to suggest that the hepatoprotective effects of co-administration of FA and/or LDR against CIS-induced hepatotoxicity are attributed to the possession of anti-oxidative, anti-inflammatory, and anti-apoptotic capabilities.

Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties.

Elicitation through abiotic stress, including chemical elicitors like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metals on actinobacteria Streptomyces sp. SH-1312 for secondary metabolite production, with strong pharmacological activity, along with pharmacokinetics profile, was firstly investigated. The optimum metal stress conditions consisted of actinobacteria strain Streptomyces sp. SH-1312 with addition of mix metals (Co2+ + Zn2+) ions at 0.5 mM in Gause’s medium. Under these conditions, the stress metabolite anhydromevalonolactone (MVL) was produced, which was absent in the normal culture of strain and other metals combinations. Furthermore, the stress metabolite was also evaluated for its anti-oxidant and cytotoxic activities. The compound exhibited remarkable anti-oxidant activities, recording the IC50 value of 19.65 ± 5.7 µg/mL in DPPH, IC50 of 15.49 ± 4.8 against NO free radicals, the IC50 value of 19.65 ± 5.22 µg/mL against scavenging ability, and IC50 value of 19.38 ± 7.11 µg/mL for iron chelation capacity and the cytotoxic activities against PC3 cell lines were recorded with IC50 values of 35.81 ± 4.2 µg/mL after 24 h, 23.29 ± 3.8 µg/mL at 48 h, and 16.25 ± 6.5 µg/mL after 72 h. Further mechanistic studies have revealed that the compound MVL has shown its pharmacological efficacy by upregulation of P53 and BAX while downregulation of BCL-2 expression, indicating that MVL is following apoptosis in varying degrees. To better understand the pharmacological properties of MVL, in this work, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) were also evaluated. During ADMET predictions, MVL has displayed a safer profile in case of hepatotoxicity, cytochrome inhibition and also displayed as non-cardiotoxic. The compound MVL showed good binding energy in the molecular docking studies, and the results revealed that MVL bind in the active region of the target protein of P53 and BAX. This work triumphantly announced a prodigious effect of heavy metals on actinobacteria with fringe benefits as a key tool of MVL production with a strong pharmacological and pharmacokinetic profile.

The NO-dependent caspase signaling pathway is a target of deoxynivalenol in growth inhibition in vitro

DON is commonly found in foods and feeds; it presents health risks, especially an increase of growth inhibition in humans, particularly infants and young children. However, there are relatively few research studies devoted to the mechanism of DON-mediated growth retardation. Interestingly, our results showed that DON does not cause any significant production of ROS but results in a persistent and significant release of NO with iNOS increasing activity, mitochondrial ultrastructural changes and decreasing ΔΨm. Moreover, the significant decreases in GH production and secretion induced by DON were dose-dependent, accompanied by an increase of caspase 3, 8 and 9, IL-11, IL-lβ and GHRH. NO scavenging agent (haemoglobin) and free radical scavenging agent (N-acetylcysteine) partially reversed mitochondrial damage, and Z-VAD-FMK increased the levels of GH and decreased the levels of caspase 3, 8 and 9, while haemoglobin decreased the levels of caspase 3, 8 and 9, indicating that NO is the primary target of DON-mediated inhibition. Present research study firstly demonstrated that NO is a key mediator of DON-induced growth inhibition and plays critical roles in the interference of GH transcription and synthesis. The current research is conducive to future research on the molecular mechanisms of DON-induced growth inhibition in humans, especially children.

Phytochemical and antioxidant screening of Cocculus hirsutus and Calycopteris floribunda

Cocculus hirsutus and Calycopteris floribunda are two important Indian medicinal plants that are having multiple health benefits in traditional medicine. The current research aims to investigate the qualitative and quantitative phytochemical screening of ethanolic extracts of the selected plants using standard protocols. The Total phenolic content and total flavonoid content were estimated by Folin–Ciocalteu &amp; Aluminum chloride colorimetric methods respectively. Invitro antioxidant activity by DPPH and NO free radical scavenging assay. Results unveiled that the total phenolic content for the ethanolic extract of C. hirsutus and C. floribunda are 157.46±1.12 &amp; 113.25±1.03 GAE per gram of sample in dry weight (mg/g) and total flavonoid content was 69±1.05 &amp; 58±1.23 of RE per gram of sample in dry weight (mg/g) respectively. In the DPPH assay, ethanolic extract of C. hirsutus is effective to inhibit (71.02%) the DPPH free radicals with IC50 values 48.10µg/ml at higher doses that are comparable to standard ascorbic acid (79.26%, IC50 =38.39µg/ml) followed by C. floribunda (65.24%, IC50 =60.49µg/ml). Similarly, in the NO free radical scavenging assay, C. hirsutus (75.19%) exhibited the highest free radical scavenging activity with IC50 values of 44.43µg/ml followed by C. floribunda (71.02%, IC50 =52.14µg/ml).

Plasma activated water-induced formation of compact chicken myofibrillar protein gel structures with intrinsically antibacterial activity

The poor gel strength and microbial infection of conventional chicken myofibrillar protein (CMP) gels have severely limited the application. Here, plasma activated water (PAW) instead of normal water was used to prepare CMP gels. PAW prepared by treating deionized water with plasma jet was incubated with CMPs and followed by heating to prepare CMP gels. Effects of PAW on CMP gels were assessed in terms of basic physicochemical properties, network structure, and antibacterial activity. The results showed that PAW treatment accelerated the aggregation of CMPs and increased the strength and water holding capacity of CMP gels. Due to the presence of NO and NO2 free radicals in PAW, the prepared CMP gels were endowed with antibacterial activity against Salmonella Enteritidis and Staphylococcus aureus. The new method of PAW-induced CMP gels will have the prospect of improving the quality of gels and extending the shelf life of chicken gel products.