Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model.

Diisononyl phthalate (DiNP) has been associated with the development of allergies, asthma, and allergic airway inflammation. Through a complex interplay of signals and feedback mechanisms, the lungs communicate with the heart to ensure maintenance of homeostasis and supporting the body's metabolic demands. In the current study, we assessed the crosstalk between DiNP-induced asthma and cardiac cellular respiration, oxidative stress, apoptotic potential, and induction of oncogenic factors. Ten male BALB/c mice with a weight range of 20-30 g were divided into two groups, each comprising five mice. Group 1 (control), was administered saline orally for a duration of 30 days. In contrast, group 2 (DiNP group), received 50 mg/kg of DiNP to induce asthma. After the final administration and asthma induction, the mice were euthanized, and their hearts were excised, processed, and subjected to biochemical analyses. The DiNP group had downregulated (P < 0.05) activities of the enzymes of glycolysis, tricyclic acid cycle, and electron transport chain except the hexokinase and succinate dehydrogenase activity which were upregulate relative to control. Also, oxidative distress markers (GSH, CAT, and MDA and SOD) were also perturbed. Biomarkers of inflammation (MPO and NO) were considerably higher (P < 0.05) in the heart of DiNP-induced asthma mice as compared with the control group. Furthermore, DiNP-induced asthma group has an increased cardiac caspase-3, Bax, c-Myc and K-ras, and p53 while the Bcl2 decreased when compared with control. Overall, the findings indicate that DiNP-induced asthma impairs cardiac functions by induction of key cardiac oncogenes, downregulation of cardiac energy, transduction of enzymes, and promotion of oxidative stress and cellular death.

Impact of dietary administration of Arthrospira platensis free-lipid biomass on growth performance, body composition, redox status, immune responses, and some related genes of pacific whiteleg shrimp, Litopenaeus vannamei.

The current study aimed to assess the influence of dietary inclusion of cyanobacterium Arthrospira platensis NIOF17/003 as a dry material and as a free-lipid biomass (FL) on the growth performance, body composition, redox status, immune responses, and gene expression of whiteleg shrimp, Litopenaeus vannamei postlarvae. L. vannamei were fed five different supplemented diets; the first group was fed on an un-supplemented diet as a negative control group (C-N), the second group was fed on a commercial diet supplemented with 2% of A. platensis complete biomass as a positive control group (C-P20), whereas, the three remaining groups were fed on a commercial diet supplemented with graded amounts of FL at 1%, 2%, and 3% (FL10, FL20, and FL30, respectively). The obtained results indicated that the diet containing 1% FL significantly increased the growth performance, efficiency of consumed feed, and survival percentage of L. vannamei compared to both C-N and C-P20 groups. As for the carcass analysis, diets containing A. platensis or its FL at higher levels significantly increased the protein, lipid, and ash content compared to the C-N group. Moreover, the shrimp group fed on C-P20 and FL10 gave significantly stimulated higher digestive enzyme activities compared with C-N. The shrimp fed C-P20 or FL exhibited higher innate immune responses and promoted their redox status profile. Also, the shrimp fed a low FL levels significantly upregulated the expression of both the peroxiredoxin (Prx) and prophenoloxidase (PPO1) genes than those receiving C-N. The current results recommended that dietary supplementation with 1% FL is the most effective treatment in promoting the performance and immunity of whiteleg shrimp.

The potential use of daphnia meal as substitute for fishmeal in diets of hybrid red tilapia affects growth performance, activities of digestive enzymes, antioxidant, immune status and intestinal histological parameters.

The current study aimed to evaluate growth performance, digestive enzyme activities, antioxidant status, nonspecific immune response and intestinal histological status of red tilapia fed Daphnia meal (DM) as a substitute for fishmeal (FM). Hybrid red tilapia (Oreochromis mossambicus × Oreochromis aureus) fry (0.54 ± 0.05 g fish-1) was allocated in nylon haba cages (100 fry m-3) for 2 weeks as an acclimation period. The fish were divided into five groups (three replicates each). The experimental diets were prepared by replacing FM with DM at concentrations of 25%, 50%, 75% and 100% respectively. The results indicated that fish fed increasing levels of DM (50%-75%) experienced high growth performance, feed utilisation and protein content. The activities of digestive enzymes were significantly increased in all groups fed DM diets compared to the control. The antioxidant balance was improved by decreasing the level of malondialdehyde and increased the total antioxidant capacity, catalase, superoxide dismutase and glutathione reductase activities in the liver of fish fed DM. The nonspecific immune response, including lysozyme, alkaline phosphatase activities and total protein level improved significantly with increasing FM substitution levels by DM in a dose-dependent manner. Histometric analysis of the intestinal wall revealed an increase in the villus length, crypts depth and goblet cells number in groups fed DM meal up to 50% substitution level compared to other treatments. It may be concluded from results of this feeding trial that in the aquaculture of hybrid tilapia, FM may be substituted with up to 50% DM without compromising intestinal health, growth performance and immune status of the fish.

Opuntia monacantha: Validation of the anti-inflammatory and anti-arthritic activity of its polyphenolic rich extract in silico and in vivo via assessment of pro- and anti-inflammatory cytokines.

ETHNOPHARMACOLOGICAL RELEVANCE: Opuntia monacantha belongs to the cactus family Cactaceae and is also known by cochineal prickly pear, Barbary fig or drooping prickly pear. It was traditionally used to treat pain and inflammation. O. monacantha cladodes showed pharmacological effects such as antioxidant potential owing to the presence of certain polysaccharides, flavonoids, and phenols. AIM OF THE STUDY: This research aimed to evaluate the anti-inflammatory as well as the anti-arthritic potential of ethanol extract of Opuntia monacantha (E-OM). MATERIALS AND METHODS: In vivo edema in rat paw was triggered by carrageenan and used to evaluate anti-inflammatory activity, while induction of arthritis by Complete Freund's Adjuvant (CFA) rat model was done to measure anti-arthritic potential. In silico studies of the previously High performance liquid chromatography (HPLC) characterized metabolites of ethanol extract was performed by using Discovery Studio 4.5 (Accelrys Inc., San Diego, CA, USA) within active pocket of glutaminase 1 (GLS1) (PDB code: 3VP1; 2.30 Å). RESULTS: EOM, particularly at 750 mg/kg, caused a reduction in the paw edema significantly and decreased arthritic score by 80.58% compared to the diseased group. It revealed significant results when histopathology of ankle joint was examined at 28th day as it reduced inflammation by 18.06%, bone erosion by 15.50%, and pannus formation by 24.65% with respect to the diseased group. It restored the altered blood parameters by 7.56%, 18.47%, and 3.37% for hemoglobin (Hb), white blood count (WBC), and platelets, respectively. It also reduced rheumatoid factor RF by 13.70% with concomitant amelioration in catalase (CAT) and superoxide dismutase (SOD) levels by 19%, and 34.16%, respectively, in comparison to the diseased group. It notably decreased mRNA expression levels of COX-2, IL-6, TNF-α, IL-1, NF-κß and augmented the levels of IL-4 and IL-10 in real time PCR with respect to the diseased group and piroxicam. HPLC analysis previously performed showed that phenolic acids and flavonoids are present in E-OM. Molecular docking studies displayed pronounced inhibitory potential of these compounds towards glutaminase 1 (GLS1), approaching and even exceeding piroxicam. CONCLUSIONS: Thus, Opuntia monacantha could be a promising agent to manage inflammation and arthritis and could be incorporated into pharmaceuticals.

Predictions based on inflammatory cytokine profiling of Egyptian COVID-19 with 2 potential therapeutic effects of certain marine-derived compounds.

BACKGROUNDS: A worldwide coronavirus pandemic has affected many healthcare systems in 2019 (COVID-19). Following viral activation, cytokines and chemokines are released, causing inflammation and tissue death, particularly in the lungs, resulting in severe COVID-19 symptoms such as pneumonia and ARDS. COVID-19 induces the release of several chemokines and cytokines in different organs, such as the cardiovascular system and lungs. RESEARCH IDEA: COVID-19 and its more severe effects, such as an elevated risk of death, are more common in patients with metabolic syndrome and the elderly. Cytokine storm and COVID-19 severity may be mitigated by immunomodulation targeting NF-κB activation in conjunction with TNF- α -inhibition. In severe cases of COVID-19, inhibiting the NF-κB/TNF- α, the pathway may be employed as a therapeutic option. MATERIAL AND METHODS: The study will elaborate on the Egyptian pattern for COVID-19 patients in the first part of our study. An Egyptian patient with COVID-19 inflammatory profiling will be discussed in the second part of this article using approved marine drugs selected to inhabit the significant inflammatory signals. A biomarker profiling study is currently being performed on Egyptian patients with SARS-COV-2. According to the severity of the infection, participants were divided into four groups. The First Group was non-infected with SARS-CoV-2 (Control, n = 16), the Second Group was non-intensive care patients (non-ICU, n = 16), the Third Group was intensive care patients (ICU, n = 16), and the Fourth Group was ICU with endotracheal intubation (ICU + EI, n = 16). To investigate COVID-19 inflammatory biomarkers for Egyptian patients, several inflammatory, oxidative, antioxidant, and anti-inflammatory biomarkers were measured. The following are examples of blood tests: CRP, Ferritin, D-dimer, TNF-α, IL-8, IL-6., IL-Ib, CD8, NF-κB, MDA, and total antioxidants. RESULTS AND DISCUSSION: The results of the current study revealed many logical findings, such as the elevation of CRP, Ferritin, D-dimer, TNF- α, CD8, IL-6, IL-, NF-κB, and MDA. Where a significant increase showed in ICU group results (23.05 ± 0.30, 2.35 ± 0.86, 433.4 ± 159.3, 26.67 ± 3.51, 7.52 ± 1.48, 7.49 ± 1.04, 5.76 ± 1.31, 7.41 ± 0.73) respectively, and also ICU group results (54.75 ± 3.44, 0.65 ± 0.13, 460.2 ± 121.42, 27.43 ± 2.52, 8.63 ± 2.68, 10.65 ± 2.75, 5.93 ± 1.4, 10.64 ± 0.86) respectively, as well as ICU + EI group results (117.63 ± 11.89, 1.22 ± 0.65, 918.8 ± 159.27, 26.68 ± 2.00, 6.68 ± 1.08, 11.68 ± 6.16, 6.23 ± 0.07, 22.41 ± 1.39),respectively.The elevation in laboratory biomarkers of cytokines storm in three infected groups with remarkable increases in the ICU + EI group was due to the elevation of oxidative stress and inflammatory storm molecules, which lead to highly inflammatory responses, specifically in severe patients of COVID-19. Another approach to be used in the current study is investigating new computational drug compounds for SARS-COV-2 protective agents from the marine environment. The results revealed that (Imatinib and Indinavir) had the highest affinity toward Inflammatory molecules and COVID-19 proteins (PDB ID: -7CZ4 and 7KJR), which may be used in the future as possible COVID-19 drug candidates. CONCLUSION: The investigated inflammatory biomarkers in Egyptian COVID-19 patients showed a strong correlation between IL6, TNF-α, NF-κB, CRB, DHL, and ferritin as COVID-19 biomarkers and determined the severity of the infection. Also, the oxidative /antioxidant showed good biomarkers for infection recovery and progression of the patients.

Characterization of Sesuvium sesuvioides Using High-Performance Liquid Chromatography and Validation of Its In Vivo Anti-hyperthyroidism Effect via Suppressing Oxidative Stress and Inflammatory Markers.

Sesuvium sesuvioides was used to treat inflammation, arthritis, gout, and thyroid dysfunction. The current study evaluated the antihyperthyroidism effect of S. sesuvioides to consolidate its traditional use. High-performance liquid chromatography (HPLC) analysis of S. sesuvioides methanol extract revealed the presence of phenolics such as gallic acid (0.73 ppm/mg), benzoic acid (11.22 ppm/mg), p-coumaric acid (3.12 ppm/mg), ferulic acid (5.47 ppm/mg), cinnamic acid (3.54 ppm/mg), and sinapic acid (3.17 ppm/mg). In vivo hyperthyroidism was induced using thyroxine in vivo, which increased T3 (triiodothyronine), T4 (tetraiodothyronine), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. However, it reduced thyroid stimulating hormone (TSH), superoxide dismutase (SOD), and reduced glutathione (GSH). S. sesuvioides methanol extract alleviated thyroxine-induced intoxication in a dose-dependent manner. At a 750 mg/kg (SsCr3) dose, it reduced T3, T4, MDA, IL-6, and TNF-α by 61.23, 41.29, 45.17, 44.66, and 62.03%, respectively, and elevated TSH, SOD, and GSH by 365.52, 94.45, and 95.12%, respectively, relative to the diseased group. Further confirmation was done by histopathological examination, which showed normal thyroid histology where follicles were filled with colloids with more cytoplasmic concentrations. This activity is undoubtedly correlated to the richness of the extract by phenolic acids, as revealed by HPLC. In silico ADME/TOPKAT prediction performed on the secondary metabolites identified in S. sesuvioides methanol extract revealed acceptable pharmacodynamic, pharmacokinetic, and toxicity potential. Thus, S. sesuvioides could serve as a promising source for alleviating hyperthyroidism, which could be further incorporated into pharmaceutical preparations.

Anti-Obesity Drug Delivery Systems: Recent Progress and Challenges.

Obesity has reached an epidemic proportion in the last thirty years, and it is recognized as a major health issue in modern society now with the possibility of serious social and economic consequences. By the year 2030, nearly 60% of the global population may be obese or overweight, which emphasizes a need for novel obesity treatments. Various traditional approaches, such as pharmacotherapy and bariatric surgery, have been utilized in clinical settings to treat obesity. However, these methods frequently show the possibility of side effects while remaining ineffective. There is, therefore, an urgent need for alternative obesity treatments with improved efficacy and specificity. Polymeric materials and chemical strategies are employed in emerging drug delivery systems (DDSs) to enhance therapy effectiveness and specificity by stabilizing and controlling the release of active molecules such as natural ingredients. Designing DDSs is currently a top priority research objective with an eye towards creating obesity treatment approaches. In reality, the most recent trends in the literature demonstrate that there are not enough in-depth reviews that emphasize the current knowledge based on the creation and design of DDSs for obesity treatment. It is also observed in the existing literature that a complex interplay of different physical and chemical parameters must be considered carefully to determine the effectiveness of the DDSs, including microneedles, for obesity treatment. Additionally, it is observed that these properties depend on how the DDS is synthesized. Although many studies are at the animal-study stage, the use of more advanced DDS techniques would significantly enhance the development of safe and efficient treatment approaches for obese people in the future. Considering these, this review provides an overview of the current anti-obesity treatment approaches as well as the conventional anti-obesity therapeutics. The article aims to conduct an in-depth discussion on the current trends in obesity treatment approaches. Filling in this knowledge gap will lead to a greater understanding of the safest ways to manage obesity.

Modulation of MAPK/NF-κB Pathway and NLRP3 Inflammasome by Secondary Metabolites from Red Algae: A Mechanistic Study.

The pharmacological properties of seaweeds are diverse. No studies have been conducted on the protective effect of Galaxaura oblongata (GOE) against lippopolysaccharide (LPS)-induced inflammation in the brain. This study is divided into three phases, the first of which is the initial phase. In vitro study includes antioxidant, radical scavenging, and anti-inflammatory activities, including cyclooxygenase-1 (COX1), COX2, NO, acetylcholine inhibition, sphingosine kinase 1, tumor necrosis factor α (TNF-α), and interleukin-6, as well as antioxidant and radical-scavenging activities, including 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid. Using LPS-induced acute inflammation, the second phase was conducted in vivo. Antioxidant and anti-inflammatory assays were performed to investigate the protective role of GOE. In addition to the phytochemical analysis, the bioactive content of GOE was also investigated. In vitro results demonstrated the potential of GOE as an antioxidant, anti-inflammatory, and neuroprotective agent. A study using LPS as an induced lung injury and neuroinflammation model confirmed the in vitro results. The GOE significantly reduced inflammatory, oxidative, and neurodegenerative biomarkers based on histopathological and immuno-histochemistry results. Based on computational drug design, four target proteins were approved: nuclear factor κB, mitogen-activated protein kinases, TNF-α, and NLRP3. Using polyphenolic compounds in GOE as ligands demonstrated good alignment and affinity against the three proteins. Finally, the current study offers a new approach to developing drug leads considering GOE's protective and curative roles.

Eremophila purpurascens: Anti-oxidant, Anti-hyperglycemic, and Hepatoprotective Potential of Its Polyphenolic Rich Leaf Extract and Its LC-ESI-MS/MS Chemical Characterization and Standardization.

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.

Neuroprotective and nephroprotective effects of Ircinia sponge in polycyclic aromatic hydrocarbons (PAHs) induced toxicity in animal model: a pharmacological and computational approach.

The present study investigated the neuroprotective and nephroprotective effects of the sponge Ircinia sp. ethyl acetate extract (ISPE) against persistent aromatic pollutants in vitro and in vivo. Different exponential experimental assays were applied to this study. An in vitro study to investigate the potential therapeutic effect of ISPE using antioxidants (for example, ABTS and DPPH) and anti-Alzheimer assays (inhibition of acetylcholinesterase); the in-vivo study was designed to evaluate the protective effect of ISPE as neuroprotective and nephroprotective against the destructive effect of PAH. Several assays included oxidative assays (LPO), antioxidant biomarkers (GSH, GST), and inflammatory and neurodegenerative biomarkers (PTK,SAA). Additionally, the results were confirmed using histopathological examination. The in silico screening study improved the in vitro and in vivo findings through interaction between the aryl hydrocarbon receptor (AHR) and the polyphenolic content of ISPE extract, which was determined using LCMSM. The results and discussion showed that ISPE exhibited a promising antioxidant and anti-acetylcholinesterase activity as evidenced by IC50 values of 49.74, 28.25, and 0.18 µg/mL in DPPH, ABTS, and acetylcholinesterase inhibition assays, respectively. In vivo, the study showed that animals receiving ISPE before poly aromatic hydrocarbons administration PAHs (Prot, ISPE) showed significant amelioration in kidney functions manifested by the reduction of serum urea, uric acid, and creatinine by 40.6%, 66.4%, and 134.8%, respectively, concerning PAH-injected mice (HAA). Prot, ISPE revealed a decline in malondialdehyde (MDA) and total proteins (TP) in kidney and brain tissues by 73.63% and 50.21%, respectively, for MDA and 59.82% and 80.41%, respectively, for TP with respect to HAA. Prot, ISPE showed significant elevation in reduced glutathione (GSH) and glutathione transferase (GST) in kidney and brain tissues and reduction in the inflammatory and pre-cancerous biomarkers, namely, serum protein tyrosine kinases (PTKs) and serum amyloid A (SAA). These findings were further supported by histopathological examination of kidney and brain tissues, which revealed normal structure approaching normal control. Metabolic profiling of ISPE using LC-MS-MS showed the presence of fourteen polyphenolic compounds belonging mainly to phenolic acids and flavonoids. In silico study revealed that all the tested compounds exerted certain binding with the aryl hydrocarbon receptor, where rutin showed the best fitting (ΔG = - 7.6 kcal/mol-1) with considerable pharmacokinetic and pharmacodynamic properties revealed from in silico ADME (Absorption, Distribution, Metabolism, and Excretion) study. Hence, it can be concluded that the Ircinia sponge showed a promising protective effect versus kidney and brain toxicity triggered by PAHs.

Residue Analysis and Risk Exposure Assessment of Multiple Pesticides in Tomato and Strawberry and Their Products from Markets.

Pesticides are used on fruit and vegetable crops to obtain greater yield and quality. Residues can be detected in these crops or their products if applied pesticides do not degrade naturally. Therefore, this study aimed to estimate pesticide residues in some strawberry and tomato-based products available in the market for human consumption and associated dietary risks. Contamination with 3-15 pesticides in the tested samples was found. The total number of pesticides detected in the tested samples was 20, belonging to the group of insecticides (84%) and fungicides (16%). Pesticides of cypermethrin, thiamethoxam, chlorpyrifos, and lambda-cyhalothrin appeared at 100% in a number of samples, where the most detected was cypermethrin followed by thiamethoxam. The average values of pesticide residues detected in the tested samples ranged from 0.006 to 0.568 mg kg-1, where it was found that cypermethrin had the highest residue value and appeared in strawberry jam obtained from the market. The recovery rate of pesticides from fortified samples with pyrethroids ranged from 47.5% (fenvalerate) to 127% (lambda-cyhalothrin). Home processing of fortified tomato and strawberry samples had a significant effect on reducing residues in tomato sauce and strawberry jam, where the reduction reached 100%. The results of acute and chronic risk assessment showed that their values were much lower than 100%, indicating minimal risk of dietary intake.

Aspergillus co-cultures: A recent insight into their secondary metabolites and microbial interactions.

There is an urgent need for novel antibiotics to combat emerging resistant microbial strains. One of the most pressing resources is Aspergillus microbial cocultures. The genome of Aspergillus species comprises a far larger number of novel gene clusters than previously expected, and novel strategies and approaches are essential to exploit this potential source of new drugs and pharmacological agents. This is the first review consulting recent developments and chemical diversity of Aspergillus cocultures and highlighting its untapped richness. The analyzed data revealed that cocultivation of several Aspergillus species with other microorganisms, including bacteria, plants, and fungi, is a source of novel bioactive natural products. Various vital chemical skeleton leads were newly produced or augmented in Aspergillus cocultures, among which were taxol, cytochalasans, notamides, pentapeptides, silibinin, and allianthrones. The possibility of mycotoxin production or complete elimination in cocultivations was detected, which pave the way for better decontamination strategies. Most cocultures revealed a remarkable improvement in their antimicrobial or cytotoxic behavior due to their produced chemical patterns; for instance, weldone and asperterrin whose antitumor and antibacterial activities, respectively, were superior. Microbial cocultivation elicited the upregulation or production of specific metabolites whose importance and significance are yet to be revealed. With more than 155 compounds isolated from Aspergillus cocultures in the last 10 years, showing overproduction, reduction, or complete suppression under the optimized coculture circumstances, this study filled a gap for medicinal chemists searching for new lead sources or bioactive molecules as anticancer agents or antimicrobials.

The hepatoprotective candidates by synergistic formula of marine and terrestrial against Acetaminophen toxicity using in-vitro, in-vivo, and in silico screening approach.

Background: One of the most regularly used hepatotoxic medicines is paracetamol (acetaminophen, N-acetyl-p-aminophenol; APAP). It causes liver failure in overdoses but is safe at therapeutic dosages. Combination therapy combining many natural compounds with a synergistic impact as hepatoprotective agents has become an essential therapeutic method against various disorders. Objective: Due to the lack of literature on paracetamol's effects on hematological and hepatic status parameters in male albino mice, the main goal of this study was to compare the hepatoprotective activities of a mixture of three marine-derived polyphenolics and polysaccharides (Sargassum vulgare Bacillus oceanisediminis, and alginic acids) to Chrysanthemum extract and the mixture of them. Methods: Sargassumvulgare, Bacillus Oceanisediminis, and alginate, as well as Chrysanthemum ethanol extracts, were tested for APAP-induced liver damage. Group 1 received saline solution subcutaneously, while Group 2 received 500 mg/kg body weight/day APAP intraperitoneal. Group 3 got 200 mg/day algal extract i.p. As in group 3, group 4 got an i.p. dose of 200 mg of algal extract before the APAP dose. This group was protected by Sargassum vulgare extract. Group 5: Received 200 mg/100 g/body of Bacillus oceanisediminis extracts i.p. for one week. Group 6: Received 200 mg/body of Bacillus oceanisediminis extract i.p. for one week before APAP treatment. Alginate (p200 mg/body weight/day) was given to Group 7. As in group 7, group 8 received 200 mg/body weight/day alginate extract i.p. before APAP. Group 9: Chrysanthemum extracts 200 mg/day for a week. Group 10: got an i.p. dose of Chrysanthemum extracts for one week before the APAP dose. Group 11: Four mixed extracts (Bacillus Oceanisediminis, Sargassum vulgare, Chrysanthemum, and alginate) were i.p200 mg/day for one week as a positive (+ve) control group. Group 12: Received i.p200 mg/kg combination extract for one week before APAP. Results: Due to their synergistic antioxidant and anti-inflammatory actions, marine extracts and combinations of marine-derived extracts demonstrated a great effect against APAP toxicity, demonstrating hepatoprotective potential against APAP-induced liver damage. Conclusion: The synergy of the three marine-derived combinations may lead to novel liver toxicity prevention agents.

Enhanced and tunable femtosecond nonlinear optical properties of pure and nickel-doped zinc oxide films.

The nonlinear optical properties of pure ZnO and Ni-doped ZnO thin films are explored using the Z-scan technique at different input laser intensities and an excitation wavelength of 750 nm by 100 fs laser pulses. The pure ZnO and Ni-doped ZnO thin films were prepared by radio frequency magnetron sputtering at room temperature. A scanning electron microscope equipped with energy-dispersive x-ray spectroscopy was used to measure the thickness and composition of the thin films, while a UV-visible spectrophotometer was used to measure the linear optical properties. The structure of the thin films was measured using x-ray diffraction. Saturable absorption (SA) was observed in the pure ZnO thin film, while Ni-doped ZnO illustrated a combination of SA and reverse SA (RSA). The nonlinear absorption coefficient (ß) and nonlinear refractive index (n2) of both pure ZnO and Ni-doped ZnO thin films were found to be input laser intensity dependent. As the input laser intensity increased, the nonlinear absorption coefficient and the nonlinear refractive index of both samples increased. An enhancement of two times in the nonlinear refractive index was observed for the Ni-doped ZnO thin film compared to the pure ZnO thin film. The optical limiting behavior of pure ZnO and Ni-doped ZnO thin films was investigated, and the data demonstrated that Ni-doped ZnO thin film is a good candidate for optical limiter applications due to the presence of strong RSA.

Rutin and Quercetin Counter Doxorubicin-Induced Liver Toxicity in Wistar Rats via Their Modulatory Effects on Inflammation, Oxidative Stress, Apoptosis, and Nrf2.

The presented study was performed to verify whether rutin and/or quercetin can inhibit liver injury induced by doxorubicin (DXR) in male Wistar rats. In this study, male Wistar rats were treated via the oral route with rutin and quercetin (50 mg/kg) either alone or in combination every other day for five weeks concomitant with receiving intraperitoneal DXR (2 mg/kg) two times a week for five successive weeks. Quercetin, rutin, and their combination significantly improved the deteriorated serum AST, ALT, and ALP activities and total bilirubin level, as well as albumin, AFP, and CA 19.9 levels in DXR-injected rats. Treatments of the DXR-injected group with quercetin and rutin prevented the elevation in liver lipid peroxidation and the reduction in superoxide dismutase, glutathione-S-transferase and glutathione peroxidase activities, and glutathione content. Treatments with quercetin and rutin significantly repressed the elevated expression of liver p53 and TNF-α and enhanced Nrf2 expression. Furthermore, the treatments significantly reduced DXR-induced liver histological changes. In conclusion, rutin and quercetin either alone or in combination may have potential preventive effects against DXR-induced hepatotoxicity through inhibiting oxidative stress, inflammation, and apoptosis as well as modulating the Nrf2 expression.

Metabolic Profiling of Heliotropium crispum Aerial Parts Using HPLC and FTIR and In Vivo Evaluation of Its Anti-Ulcer Activity Using an Ethanol Induced Acute Gastric Ulcer Model.

This study explored the antiulcer potential of methanol extract and fractions of Heliotropium crispum roots against the ethanol-induced gastric ulcer model in rats. Metabolic profiling of H. crispum aerial parts using Fourier-transform infrared spectroscopy (FTIR) revealed the presence of different metabolites with various functional groups. Meanwhile, High Performance Liquid Chromatography (HPLC) revealed the presence of three main peaks assigned to myricetin, quercetin, and kaempferol. In vivo, antiulcer activity results showed that the disease control group displayed five tiny ulcers less than 2 mm in diameter in addition to two hemorrhagic streaks. However, in the standard control group, only one small ulcer was visible for the total methanol extract. Gastric tissues and contents were evaluated to determine many parameters such as ulcer score, ulcer index, percentage inhibition of ulcer, gastric pH, gastric juice volume, and acidity. Results were endorsed by histopathological evaluation; gastric pH and mucus content were significantly increased, but gastric juice volume was significantly decreased. All fractions showed a significant decrease in ulcer index and % inhibition except the n-hexane fraction, whose results were insignificant compared to the disease control group. Thus, it was concluded that H. crispum shows an antiulcer effect by decreasing gastric juice volume and acidity, whereas gastric pH and mucus contents were increased that is attributed to the synergistic action of its detected polyphenolic compounds.

Multi-Step In Silico Discovery of Natural Drugs against COVID-19 Targeting Main Protease.

In continuation of our antecedent work against COVID-19, three natural compounds, namely, Luteoside C (130), Kahalalide E (184), and Streptovaricin B (278) were determined as the most promising SARS-CoV-2 main protease (Mpro) inhibitors among 310 naturally originated antiviral compounds. This was performed via a multi-step in silico method. At first, a molecular structure similarity study was done with PRD_002214, the co-crystallized ligand of Mpro (PDB ID: 6LU7), and favored thirty compounds. Subsequently, the fingerprint study performed with respect to PRD_002214 resulted in the election of sixteen compounds (7, 128, 130, 156, 157, 158, 180, 184, 203, 204, 210, 237, 264, 276, 277, and 278). Then, results of molecular docking versus Mpro PDB ID: 6LU7 favored eight compounds (128, 130, 156, 180, 184, 203, 204, and 278) based on their binding affinities. Then, in silico toxicity studies were performed for the promising compounds and revealed that all of them have good toxicity profiles. Finally, molecular dynamic (MD) simulation experiments were carried out for compounds 130, 184, and 278, which exhibited the best binding modes against Mpro. MD tests revealed that luteoside C (130) has the greatest potential to inhibit SARS-CoV-2 main protease.

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.

Malva parviflora Leaves and Fruits Mucilage as Natural Sources of Anti-Inflammatory, Antitussive and Gastro-Protective Agents: A Comparative Study Using Rat Models and Gas Chromatography.

Malva parviflora L., Little mallow, has been traditionally used as an alternative food source. It acts as a medicinal herb containing a potential source of mucilage thus herein; we aimed to assess the toxicity, anti-inflammatory, antitussive and gastro-protective actions of M. parviflora mucilage extracted from its leaves (MLM) and fruit (MFM). Toxicity studies were investigated by in vitro hemolytic assay whereas acute anti-inflammatory and antitussive activities were assessed by carrageenan-induced paw edema and sulphur dioxide induced cough model in rats, respectively. Gastro-protective effects were studied using ethanol induced acute and chronic gastric ulcer rat models. Their metabolic profiles were determined using gas chromatography. The results revealed that MLM and MFM were non-toxic towards human erythrocytes and their lethal doses were found to be greater than 5 g/kg. Pretreatment with MLM (500 mg/kg) and MFM (500 mg/kg) significantly reduced the carrageenan-induced paw thickness (p < 0.001). Maximum edema inhibition (%) was observed at 4 h in diclofenac sodium (39.31%) followed by MLM (27.35%) and MFM (15.68%). Animals pretreated with MLM (500 mg/kg) significantly lower the cough frequency in SO2 gas induced cough models in contrast to control. Moreover, MLM at doses of 250 and 500 mg/kg reduced the ethanol induced gastric mucosal injuries in acute gastric ulcer models presenting ulcer inhibition of 23.04 and 38.74%, respectively. The chronic gastric ulcer model MFM (500 mg/kg) demonstrated a remarkable gastro-protective effect showing 63.52% ulcer inhibition and results were closely related to standard drug sucralfate. In both models, MLM and MFM decreased gastric juice volume and total acidity in addition to an increased gastric juice pH and gastric mucous content justifying an anti-secretary role of this mucilage that was further confirmed by histopathological examination. Meanwhile, GC analyses of the mucilage revealed their richness with natural as well as acidic monosaccharides. It is concluded that MLM and MFM can be used therapeutically for the management of inflammation, cough and gastric ulcer.