Antimicrobial screening of pecan shell extract and efficacy of pecan shell extract-pullulan coating against Listeria monocytogenes, Salmonella enterica, and Staphylococcus aureus on blueberries.

Pecan shell is considered an agricultural waste; however, it contains various bioactive compounds with potential inhibitory effect against microorganisms. This study evaluated the antimicrobial efficacy of pecan shell extract (PSE) in vitro using disc-diffusion method and in vivo on blueberries as an antimicrobial coating using pullulan. For in vitro study, 5 and 10 % of aqueous (A-PSE) or ethanol pecan shell extract (E-PSE) incorporated into pullulan film were tested against different bacterial and fungal strains. Pullulan film disc was used as control. The diameter of growth inhibition (mm) around discs was measured. For in vivo study, PSE-P (5 % w/v aqueous pecan shell extract+5 % w/v pullulan), P (5 % w/v pullulan) or control (water) were spray coated on blueberries inoculated (∼5 log CFU/g) with Listeria monocytogenes, Salmonella enterica or Staphylococcus aureus; and stored at 4 °C, 50 ± 10 % RH for 15 days. The effect of antimicrobial coating against pathogens and its impact on quality during storage were determined. A-PSE and E-PSE films were more effective against Gram-positive bacteria and showed no antifungal effect at tested concentrations when evaluated in vitro. Immediately after coating on blueberries, PSE-P significantly reduced Listeria monocytogenes by 2 log CFU/g and lowered survival until day 5 than control or P. Native aerobic microbial population was reduced (P < 0.05) by 0.7 log CFU/g immediately after coating. PSE-P coating or storage time had no significant effect (P > 0.05) on the survival of S. enterica, S. aureus and native fungal population. PSE-P maintained the firmness of blueberry with no significant effect on its color, TSS, and pH during 15 days storage. PSE-P significantly reduced (P < 0.05) the spoilage rate by 21 % than control (28.5 %) and P (37 %); and minimized (P < 0.05) weight loss during storage. Pecan shell extracts show promise as a potential antimicrobial compound whose application on various food products or packaging material could be further explored.

In silico identification and in vitro validation of alpha-hederin as a potent inhibitor of Wnt/ß-catenin signaling pathway in breast cancer stem cells.

Cancer stem cells (CSCs) play a vital role in metastasis, recurrence and chemoresistance in breast cancer. ß-catenin, which is a frequently over activated protein in CSCs, binds to T-cell factor/lymphoid enhancer factor (Tcf/Lef) family transcription factors leading to ectopic expression of Wnt pathway responsive genes necessary for the maintenance and action of CSCs. With the aim of identifying a small molecules that can effectively eliminate CSCs, molecular docking studies were performed against the Tcf/Lef binding hotspot on ß-catenin using a library of 100 natural or synthetic small molecules. Small molecule ligands giving docking energy better than - 7 kcal/mol were further investigated by binding interactions analysis and molecular dynamics (MD) simulations. These compounds were then investigated in vitro, for cytotoxicity against CSCs isolated from MDA-MB-231 triple negative breast cancer cells. Alpha-hederin (AH) was identified as the only compound in the selected library that has cytotoxicity against breast CSCs. AH was further investigated for it's ability to regulate Wnt pathway target genes (Cyclin D1 and CD44)and the tumor suppressor p53by real-time quantitative PCR. Absorption, distribution, metabolism, excretion and toxicity properties of the AH was predicted in silico. AH significantly down regulated the transcription of Cyclin D1 and CD44 while up-regulating the transcription of p53. AH was predicted to have acceptable drug likeness. Although AH is currently known to inhibit the growth of various cancer cells in vitro, present study demonstrated for the first time that it is a potent inhibitor of Wnt/ß-catenin signaling pathway and induce apoptosis in breast CSCs.

Himalayan lichen biomass for green synthesis of silver nanocolloids: growth kinetics, effect of pH and metal sensing.

Lichen is one of the most abundant non-vascular biomasses; however, a systematic study on the application of biomass in nanomaterial synthesis is very limited. In this study, an aqueous lichen extract was obtained from Hypotrachyna cirrhata, one of the most abundant Himalayan lichen biomasses, using a simple cold percolation method. The effects of extract-to-silver nitrate mixing ratio, pH and waiting time on the growth and stability of nanoparticles were systematically explored. The rate constant for bio-reduction was found to be 5.3 × 10-3 min-1. Transmission electron microscopy showed a narrow particle size distribution with a mean particle size of 11.1 ± 3.6 nm (n = 200). The X-ray diffraction and selected area electron diffraction techniques confirmed the formation of cubic crystals. The synthesized colloidal solution showed excellent response to Hg2+ and Cu2+ ions in spiked water samples. The limit of detection and calibration sensitivity for Hg2+ and Cu2+ ions were found to be 1 and 5 mg l-1 and 2.9 × 10-3 and 1.6 × 10-3 units ppm-1, respectively. These findings suggested that spherical silver nanoparticles with a narrow particle size distribution can be synthesized on a laboratory scale using an aqueous H. cirrhata lichen extract, and the colloidal solution can be used for the detection of selected heavy metals in water samples.

Radical Scavenging, Anti-Inflammatory, and Hepatoprotective Activities of Pentacyclic Triterpene isolated from Rosa webbiana.

INTRODUCTION: Rosa webbiana (RW) Wall Ex. Royle is used in traditional medicine in Pakistan for the treatment of several diseases including jaundice. To date, only neuroprotective potential of the plant has been evaluated. OBJECTIVE: The current study was designed to isolate bioactive compound(s) and investigate its possible radical scavenging, anti-inflammatory and hepatoprotective activities. METHODS: Column chromatography was done to isolate compounds from the chloroform fraction of RW. The compound was characterized by mass spectrometry, 1H-NMR, and 2D-NMR spectroscopy. Radical scavenging activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) assays, while anti-inflammatory potential was evaluated via xylene-induced ear edema and carrageenan-induced paw edema models. For hepatoprotection, CCl4-induced model in mice was used. RESULTS: A triterpene compound (3α, 21ß-dihydroxy-olean-12-ene) was isolated from RW fruits (ARW1). The compound exhibited DPPH and H2O2 scavenging activities 61 ± 1.31% and 66 ± 0.48% respectively at 500 µg/ml. ARW1 (at 50 mg/kg) exhibited 62.9 ± 0.15% inhibition of xylene-induced ear edema and 66.6 ± 0.17% carrageenan-induced paw edema in mice. In CCl4-induced hepatotoxic mice, ARW1 significantly countered elevation in alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (T.B), and reduction in total protein (T.P) levels. Liver histomorphological study supported the serum biochemical profile for hepatoprotection. Moreover, ARW1 significantly attenuated the toxic changes in body and liver weight induced by CCl4. CONCLUSION: The compound ARW1 exhibited anti-radical, anti-inflammatory and hepatoprotective effects. The anti-inflammatory and hepatoprotective activities may be attributed to anti-oxidant potential of the compound.

Potent ROS inhibitors from Zanthoxylum armatumDC of Nepali origin.

A bioassay-guided isolation on the plant Zanthoxylum armatum DC yielded compounds tambulin (1), and prudomestin (2), from ethyl acetate fraction which showed the highest ROS inhibiting activity (IC50 = 17.8 ± 1.1 µg/mL). Structure elucidation of pure compounds was done using mass and NMR spectroscopic techniques. Compounds 1 and 2 revealed potent ROS inhibition with IC50 = 7.5 ± 0.3 and 1.5 ± 0.3 µg/mL, respectively, as compared to standard ibuprofen (IC50 = 11.2 ± 1.9 µg/mL). Likewise, both compounds 1 and 2 showed potent antioxidant activity with IC50 = 32.65 ± 0.31 and 26.96 ± 0.19 µg/mL, respectively. In vitro studies were supported by molecular docking and drug-likeliness properties. In silico studies of 1 and 2 with cyclooxygenase-2 (COX-2) showed perfect binding affinity with binding energies of -8.4 and -8.6 kcal/mol, respectively, comparable to standard ibuprofen (-7.7 kcal/mol). Drug likeness and ADMET showed higher gastrointestinal absorption of 1 and 2 and no toxic impact.

Stabilization of ginger essential oil Pickering emulsions by pineapple cellulose nanocrystals.

Pickering emulsions (PE) are systems made up of two incompatible fluids, these are stabilized by solid organic or inorganic particles located on their interface. Cellulose nanocrystals (CNCs) are sustainable and biocompatible value-added naturally occurring biomolecules which are being investigated as PE stabilizers in the cosmetic, food, and pharmaceutical industries. The objective of this research was to investigate the efficacy of pineapple cellulose nanocrystals as stabilizers for a ginger essential oil-in-water Pickering emulsion. Anionic pineapple cellulose nanocrystals were prepared by acid hydrolysis. Ginger essential oil-in-water emulsions were prepared by ultrasonication. Pineapple CNC produced stable Pickering emulsions with surface average droplet size of 4.3 µm-6.2 µm, high negative zeta potential, high viscosity, and high adsorption at the interface. Pickering emulsions by ultrasonication were stable against droplet coalescence, phase separation, and droplet flocculation for at least 8 weeks at 25 °C or 40 °C at various droplet sizes. The emulsion droplet size and volume density (droplet size distribution) were evaluated by varying the particle concentration (CNC 0.25 g/100 ml or 0.50 g/100 ml) and/or oil fraction (10-20 g/100 ml). At constant oil fraction, the emulsion viscosity increased as the nanocrystal concentration increased. The cellulose nanocrystal-stabilized ginger oil-Pickering emulsions exhibited shear-thinning characteristics of a pseudo-plastic fluid. Pineapple nanocellulose crystal -stabilized ginger oil-Pickering emulsions exhibited high stability with a creaming index of zero. CNC was found to be an effective Pickering stabilizer for oil-in-water emulsions in various food applications.

Effect of Type of Mulch on Microbial Food Safety Risk on Cucumbers Irrigated with Contaminated Water.

Mulches are used to block light and retain soil moisture which may affect the survival of bacterial pathogens on soil. This study examined the effectiveness of different types of mulches to minimize microbial risk from contaminated water used for irrigation of cucumbers. A production bed of 120 ft2 with 18 beds (30 ft long) covered with five different types of mulch (paper, paper with fertilizer incorporated (PF), maize-based mulch, biodegradable plastic covering, and conventional plastic) including three beds with no cover was planted with Dasher 2 Variety cucumber. Soil samples from each bed were collected for the first five weeks to examine natural E. coli and coliforms. Well water contaminated with or without nalidixic acid-resistant mutant of E. coli (8 Log CFU/mL) was used for drip irrigation for 7 days before harvesting. Prior to irrigation with contaminated water, naturally present E. coli and coliform in the soil samples with or without mulch were in the range of 3.45-3.78 Log CFU/g and 4.18-5.31 Log CFU/g, respectively. E. coli levels on cucumbers harvested from mulched beds and irrigated with contaminated irrigation water had significantly higher (P < 0.05) levels of E. coli as compared with samples from similar beds irrigated with noncontaminated water. However, Cucumber, harvested within each irrigation water quality were not significantly different regardless of the type of mulch with E. coli levels from 1.72 to 3.30 Log CFU/cm2 (contaminated water) and 0.28-1.86 Log CFU/cm2 (noncontaminated water). A significant die-off of inoculated E. coli was observed on cucumber within 3 days (>1.17 Log CFU/cm2) and >1.38 Log CFU/cm2 after 4 days. Beds with maize mulch were effective on minimizing E. coli contamination on cucumber from contaminated irrigation water.

Effect of storage temperature and produce type on the survival or growth of Listeria monocytogenes on peeled rinds and fresh-cut produce.

Whole and fresh-cut produce are minimally processed and susceptible to microbial contamination. This study evaluated the survival or growth of L. monocytogenes on peeled rinds, and fresh-cut produce at different storage temperatures. Fresh-cut fruits and vegetables, including cantaloupe, watermelon, pear, papaya, pineapple, broccoli, cauliflower, lettuce, bell pepper, and kale (25 g pieces) were spot inoculated with 4 log CFU/g of L. monocytogenes and stored at 4 or 13°C for 6 days. Cantaloupe and bell pepper rind disks (20 cm2), mimicking whole produce were inoculated with low inoculum level (4 log CFU/mL) and high inoculum level (6 log CFU/mL) and stored at 24°C up to 8 days and 4°C up to 14 days, respectively. L. monocytogenes counts on fresh-cut pear samples stored at 4°C increased significantly by 0.27 log CFU/g. However, Listeria levels on kale (day 4), cauliflower (day 6), and broccoli (day 2) were significantly reduced by 0.73, 1.18, and 0.80 log CFU/g, respectively, at 4°C. At 13°C, the bacterial counts increased significantly after a day of storage on fresh-cut watermelons (increasing by 1.10 log CFU/g) and cantaloupes (increasing by 1.52 log CFU/g). Similar increases were observed on pears (1.00 log CFU/g), papayas (1.65 log CFU/g), and green bell peppers (1.72 log CFU/g). Pineapple samples did not support the growth of L. monocytogenes at 13°C with a significant reduction of 1.80 log CFU/g by day 6. L. monocytogenes levels significantly increased in fresh-cut lettuce at 13°C but remained stable on kale, cauliflower, and broccoli after 6 days of storage. Stable population was observed also on cantaloupe rinds up to 8 days at 24°C. While on the outer surface of bell peppers, the population level decreased below the detectable limit of the test (10 CFU/20 cm2) after 14 days of storage at 4°C. The results demonstrated variable survival behavior of L. monocytogenes on fresh-cut produce with produce type and storage temperature.

Identification of potential human pancreatic α-amylase inhibitors from natural products by molecular docking, MM/GBSA calculations, MD simulations, and ADMET analysis.

Human pancreatic α-amylase (HPA), which works as a catalyst for carbohydrate hydrolysis, is one of the viable targets to control type 2 diabetes. The inhibition of α-amylase lowers blood glucose levels and helps to alleviate hyperglycemia complications. Herein, we systematically screened the potential HPA inhibitors from a library of natural products by molecular modeling. The modeling encompasses molecular docking, MM/GBSA binding energy calculations, MD simulations, and ADMET analysis. This research identified newboulaside B, newboulaside A, quercetin-3-O-ß-glucoside, and sasastilboside A as the top four potential HPA inhibitors from the library of natural products, whose Glide docking scores and MM/GBSA binding energies range from -9.191 to -11.366 kcal/mol and -19.38 to -77.95 kcal/mol, respectively. Based on the simulation, among them, newboulaside B was found as the best HPA inhibitor. Throughout the simulation, with the deviation of 3Å (acarbose = 3Å), it interacted with ASP356, ASP300, ASP197, THR163, ARG161, ASP147, ALA106, and GLN63 via hydrogen bonding. Additionally, the comprehensive ADMET analysis revealed that it has good pharmacokinetic properties having not acutely toxic, moderately bioavailable, and non-inhibitor nature toward cytochrome P450. All the results suggest that newboulaside B might be a promising candidate for drug discovery against type 2 diabetes.

Evaluation of the Effectiveness of Aeration and Chlorination during Washing to Reduce E. coli O157:H7, Salmonella enterica, and L. innocua on Cucumbers and Bell Peppers.

The attachment strength of bacteria to surfaces can affect the efficacy of sanitizers during washing. This study aimed to determine the effectiveness of chlorination and aeration in the removal of pathogens from the surface of produce. Cucumbers and bell peppers were inoculated with Listeria innocua, Escherichia coli O157:H7, or Salmonella enterica; afterwards, the produce was washed with or without chlorinated water (100 ppm) for 3 min in combination with or without aeration. Cucumbers washed with chlorinated water, with or without aeration, presented significant reductions of L. innocua (3.65 log CFU/cm2 and 1.13 log CFU/cm2, respectively) (p < 0.05). Similarly, bell peppers washed in chlorinated water with aeration (1.91 log CFU/g) and without aeration (2.49 log CFU/g) presented significant reductions of L. innocua. A significant reduction of L. innocua was observed on bell peppers washed with non-chlorinated water with aeration (2.49 log CFU/g) (p < 0.05). Non-chlorinated water was also effective in significantly reducing the level of Salmonella enterica (p < 0.05) on cucumbers and bell peppers. Washing with chlorinated water with aeration reduced Salmonella enterica levels from 4.45 log CFU/cm2 on cucumbers to below the detectable limit (0.16 log CFU/cm2). The highest reduction of Salmonella enterica from bell peppers occurred after washing with chlorinated water with aeration (2.48 log CFU/g). E. coli O157:H7, L. innocua, and Salmonella enterica levels present in non-chlorinated water after washing contaminated produce with or without aeration were significantly greater than those in chlorinated water (p < 0.05). After treatment, the population levels of all pathogens in chlorinated water with or without aeration were below the detectable limit for bell peppers (<1.10 log CFU/mL) and cucumbers (<1.20 log CFU/mL). Using chlorine in combination with forced aeration during washing minimizes cross-contamination of bacterial pathogens.

Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein.

The in silico method has provided a versatile process of developing lead compounds from a large database in a short duration. Therefore, it is imperative to look for vaccinations and medications that can stop the havoc caused by SARS-CoV-2. The spike protein of SARS-CoV-2 is required for the viral entry into the host cells, hence inhibiting the virus from fusing and infecting the host. This study determined the binding interactions of 36 flavonoids along with two FDA-approved drugs against the spike protein receptor-binding domain of SARS-CoV-2 through molecular docking and molecular dynamics (MD) simulations. In addition, the molecular mechanics generalized Born surface area (MM/GBSA) approach was used to calculate the binding-free energy (BFE). Flavonoids were selected based on their in vitro assays on SARS-CoV and SARS-CoV-2. Our pharmacokinetics study revealed that cyanidin showed good drug-likeness, fulfilled Lipinski's rule of five, and conferred favorable toxicity parameters. Furthermore, MD simulations showed that cyanidin interacts with spike protein and alters the conformation and binding-free energy suited. Finally, an in vitro assay indicated that about 50% reduction in the binding of hACE2 with S1-RBD in the presence of cyanidin-containing red grapes crude extract was achieved at approximately 1.25 mg/mL. Hence, cyanidin may be a promising adjuvant medication for the SARS-CoV-2 spike protein based on in silico and in vitro research.

Effect of ultraviolet light treatment on microbiological safety and quality of fresh produce: An overview.

Fresh and fresh-cut fruits and vegetables have been associated in several foodborne illness outbreaks. Although investigations from those outbreaks reported that the contamination with pathogenic microorganisms may occur at any point in the farm to fork continuum, effective control strategies are still being widely investigated. In that direction, the concept of hurdle technology involving a sequence of different interventions have been widely explored. Among those interventions, ultraviolet (UV) light alone or in combination with other treatments such as use of organic acids or sanitizer solutions, has found to be a promising approach to maintain the microbiological safety and quality of fresh and fresh-cut produce. Recent advances in using UV as a part of hurdle technology on the safety of fresh produce at different stages are presented here. Furthermore, this review discusses the mechanism of UV induced antimicrobial activity, factors that influence antimicrobial efficacy and its effect on produce. In addition, the challenges, and prospects of using UV irradiation as an intervention treatment were also discussed.

Antioxidant, Antibacterial, Antidiabetic Potential, and In silico Analysis of Rhus chinensis from Western Nepal.

BACKGROUND: Rhus chinensis Mill, indigenous wild fruit primarily found in the hilly region of Nepal. The ripe fruit is very sour and considered medicinal as a remedy for colic pain. In addition, their astringent and styptic qualities are used internally to treat illnesses such as diarrhea and hemorrhage. Also, they are used as a common component of polyherbal medications for diabetic mellitus. OBJECTIVES: This work aimed to determine the total phenolic and flavonoid content, antioxidant, antibacterial, α-glucosidase, and α-amylase inhibition activity of the crude extract and fractions of Rhus chinensis Mill. Additionally, molecular docking of compounds from Rhus chinensis was performed. METHODS: Folin Ciocalteu's (FC) reagent was used to estimate total phenolic content. Likewise, the aluminium trichloride method was applied to determine total flavonoid content. A 2,2-diphenyl-1- picrylhydrazyl (DPPH) free radical scavenging assay was performed for the antioxidant activity. Furthermore, the substrate-based enzyme inhibition assay was carried out for α-glucosidase and α- amylase inhibition activity of R. chinensis. P-nitrophenyl-α-D-glucopyranoside (PNPG) and 2- Chloro-4-Nitrophenyl-α-D-Maltotrioside (CNPG3) were used as substrates for α-glucosidase and α- amylase inhibition assay, respectively. Similarly, the well-diffusion method was used for the antibacterial activity. Autodock vina was used to perform molecular docking. RESULTS: The total phenolic and flavonoid content of R. chinensis fruit were 117.092±1.1 mg GAE/g and 62.41±1.23 mg QE/g, respectively. The IC50 value for antioxidant activity of the crude extract and its fractions ranged from 3.12±1.15µg/mL to 50.85±2.10µg/mL. Similarly, the IC50 for α- glucosidase inhibition ranged from2.33±1.01µg/mL to 28.34±2.79µg/mL. Likewise, The IC50 of R. chinensis crude methanolic extract against α-amylase was 120.3±1.382µg/mL. The antibacterial activity of R. chinensis was effective against gram-positive bacteria; Staphylococcus aureus (ZOI=11.0) and Bacillus subtilis (ZOI=9.0). Quercetin-3-O-rhamnoside and Myricetin-3-Orhamnoside showed excellent binding to the active site of protein with binding energy -9.4kcal/mol and -9.6kcal/mol, respectively. CONCLUSION: Rhus chinensis Mill is a potent antioxidant and inhibits enzymes; α-glucosidase and α- amylase. In addition, the methanolic extract of this plant shows antibacterial activity. However, further research is required to determine the inhibiting compounds.

Novel Approaches to Environmental Monitoring and Control of Listeria monocytogenes in Food Production Facilities.

Listeria monocytogenes is a serious public health hazard responsible for the foodborne illness listeriosis. L. monocytogenes is ubiquitous in nature and can become established in food production facilities, resulting in the contamination of a variety of food products, especially ready-to-eat foods. Effective and risk-based environmental monitoring programs and control strategies are essential to eliminate L. monocytogenes in food production environments. Key elements of the environmental monitoring program include (i) identifying the sources and prevalence of L. monocytogenes in the production environment, (ii) verifying the effectiveness of control measures to eliminate L. monocytogenes, and (iii) identifying the areas and activities to improve control. The design and implementation of the environmental monitoring program are complex, and several different approaches have emerged for sampling and detecting Listeria monocytogenes in food facilities. Traditional detection methods involve culture methods, followed by confirmation methods based on phenotypic, biochemical, and immunological characterization. These methods are laborious and time-consuming as they require at least 2 to 3 days to obtain results. Consequently, several novel detection approaches are gaining importance due to their rapidness, sensitivity, specificity, and high throughput. This paper comprehensively reviews environmental monitoring programs and novel approaches for detection based on molecular methods, immunological methods, biosensors, spectroscopic methods, microfluidic systems, and phage-based methods. Consumers have now become more interested in buying food products that are minimally processed, free of additives, shelf-stable, and have a better nutritional and sensory value. As a result, several novel control strategies have received much attention for their less adverse impact on the organoleptic properties of food and improved consumer acceptability. This paper reviews recent developments in control strategies by categorizing them into thermal, non-thermal, biocontrol, natural, and chemical methods, emphasizing the hurdle concept that involves a combination of different strategies to show synergistic impact to control L. monocytogenes in food production environments.

Favipiravir in SARS-CoV-2 Infection: Is it Worth it?

Favipiravir is a potential antiviral drug undergoing clinical trials to manage various viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Favipiravir possesses antiviral properties against RNA viruses, including SARS-CoV-2. Unfortunately, these viruses do not have authorized antiviral drugs for the management of diseases resulting from their infection, hence the dire need to accentuate the discovery of antiviral drugs that are efficacious and have a broad spectrum. Favipiravir acts primarily by blocking inward and outward movements of the virus from cells. Favipiravir is a prodrug undergoing intracellular phosphorylation and ribosylation to form an active form, favipiravir-RTP, which binds viral RNA-dependent RNA polymerase (RdRp). Considering the novel mechanism of favipiravir action, especially in managing viral infections, it is vital to pay more attention to the promised favipiravir hold in the management of SARS-CoV-2, its efficacy, and dosage regimen, and interactions with other drugs. In conclusion, favipiravir possesses antiviral properties against RNA viruses, including COVID- 19. Favipiravir is effective against SARS-CoV-2 infection through inhibition of RdRp. Pre-clinical and large-scalp prospective studies are recommended for efficacy and long-term safety of favipiravir in COVID-19.

C-H Bond Functionalization under Electrochemical Flow Conditions.

Electrochemical C-H functionalization is a rapidly growing area of interest in organic synthesis. To achieve maximum atom economy, the flow electrolysis process is more sustainable. This allows shorter reaction times, safer working environments, and better selectivities. Using this technology, the problem of overoxidation can be reduced and less emergence of side products or no side products are possible. Flow electro-reactors provide high surface-to-volume ratios and contain electrodes that are closely spaced where the diffusion layers overlap to give the desired product, electrochemical processes can now be managed without the need for a deliberately added supporting electrolyte. Considering the importance of flow electrochemical C-H functionalization, a comprehensive review is presented. Herein, we summarize flow electrolysis for the construction of C-C and C-X (X=O, N, S, and I) bonds formation. Also, benzylic oxidation and access to biologically active molecules are discussed.

Antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities of pentacyclic triterpenes isolated from Ziziphus oxyphylla Edgew.

Ziziphus oxyphylla Edgew is in folk use in Pakistan as an analgesic, anti-inflammatory, and liver ailments. Therefore, we have investigated antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities of the isolated compounds (ceanothic acid and zizybrenalic acid) from the chloroform fraction of Z. oxyphylla. Ceanothic acid and zizybrenalic acid showed significant DPPH and H2O2 scavenging activity as compared to control. In the acute toxicity study, ceanothic acid and zizybrenalic acid showed no toxic effects upto 200 mg/kg. The antinociceptive activity shown by ceanothic acid and zizybrenalic acid at 50 mg/kg was 64.28% and 65.35% compared to diclofenac sodium (72.3%) at 50 mg/kg. The percent inhibition of xylene-induced ear edema exhibited by ceanothic acid and zizybrenalic acid at 50 mg/kg was 51.33% and 58.66%, respectively, as compared to diclofenac sodium (72.66%). Both the isolated compounds exhibited inhibition of carrageenan-induced paw edema as compared to control. Hepatoprotection exhibited by zizybrenalic acid was more pronounced than ceanothic acid as observed from the decrease in carbon tetrachloride (CCl4)-induced elevation of serum biomarkers, antioxidant enzymes and lipid peroxidation. Furthermore, zizybrenalic acid produced a marked decline in CCl4-induced prolongation of phenobarbital-induced sleeping duration. Zizybrenalic acid exhibited 55.4 ± 1.37% inhibition of hypotonic solution-induced hemolysis compared to sodium salicylate (75.6 ± 2.15%). The histopathological damage caused by CCl4 was also countered by the administration of ceanothic acid and zizybrenalic acid. Ceanothic acid and zizybrenalic acid exhibited antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities. Zizybrenalic acid exhibited better antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activity than ceanothic acid.

Isolation, Biological Evaluation, and Molecular Docking Studies of Compounds from Sophora mollis (Royle) Graham Ex Baker.

The Sophora mollis is one of the best anti-inflammatory, antioxidant, and anticancerous plant; therefore, the isolated chemical constituents, that is, scopoletin (1), pinitol (2), 2-propenoic acid, 3-(3,4-dihydroxyphenyl)-octacosyl ester (3), betulin (4), and ß-sitosterol glucoside (5) were tested for these folklores. The structures of the isolated compounds were confirmed by 1H NMR, 13C NMR, 2D-NMR, and mass spectral data. The anti-inflammatory, anticancer, antiglycation, and antioxidant activities of compounds 1-5 were evaluated using different assays. Compound 1 exhibited significant anti-inflammatory effect as it reduced edema of the paw (83.98%), which is more potent than the standard drug (ibuprofen) (which showed an inhibition percentage of 73.22% a), followed by compound 3. Furthermore, compound 3 showed significant free-radical scavenging activity using the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free-radical assay. Percentage inhibition of DPPH recorded was 95.646 ± 0.003, 94.766 ± 0.014, and 94.516 ± 0.011% at concentrations of 400, 200, and 100 µg/mL, respectively. Evaluation of anticancer activity of isolated compounds reveals weak effect against HeLa and 3T3 cell lines. Docking studies of the most active compound into the binding sites of cyclooxygenase isoforms showed a better antagonistic potential against COX-1 than the COX-2 isoform.

Management of SARS-CoV-2 Infection: Key Focus in Macrolides Efficacy for COVID-19.

Macrolides (e.g., erythromycin, fidaxomicin, clarithromycin, and azithromycin) are a class of bacteriostatic antibiotics commonly employed in medicine against various gram-positive and atypical bacterial species mostly related to respiratory tract infections, besides they possess anti-inflammatory and immunomodulatory effects. Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). It was first detected in Wuhan, Hubei, China, in December 2019 and resulted in a continuing pandemic. Macrolides have been extensively researched as broad adjunctive therapy for COVID-19 due to its immunostimulant abilities. Among such class of drugs, azithromycin is described as azalide and is well-known for its ability to decrease the production of pro-inflammatory cytokines, including matrix metalloproteinases, tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8. In fact, a report recently published highlighted the effectiveness of combining azithromycin and hydroxychloroquine for COVID-19 treatment. Indeed, it has been underlined that azithromycin quickly prevents SARS-CoV-2 infection by raising the levels of both interferons and interferon-stimulated proteins at the same time which reduces the virus replication and release. In this sense, the current review aims to evaluate the applications of macrolides for the treatment of COVID-19.

Antioxidant Properties of Pecan Shell Bioactive Components of Different Cultivars and Extraction Methods.

Pecan shells are a rich source of various bioactive compounds with potential antioxidant and antimicrobial properties. This study investigated the effect of pecan variety and method extraction on the antioxidant property of shell extracts. Twenty different varieties of pecan shells were subjected to either aqueous or ethanolic extraction and were examined for total phenolics and antiradical activity. The phenolic content and antiradical activity of shell extracts were significantly (p < 0.05) varied with different pecan cultivars. The total phenolic content of ethanol extracts ranged from 304.2 (Caddo) to 153.54 (Cherokee) mg GAE/g of dry extract and was significantly greater (p < 0.05) than those obtained by aqueous extraction. The antiradical activity of ethanol extracts ranged from 840.6 (Maramec) to 526.74 (Caper Fear) mg TEg-1, while aqueous extracts ranged from 934.9 (Curtis) to 468.3 (Elliot) mg TEg-1. Chemical profiling of the crude and acid hydrolyzed extracts was performed by reverse phase high performance liquid chromatography and flow injection electrospray ionization mass spectrometry. Lignin degradation products such as lignols, dilignols, trilignols, and oligolignols were found to be the major components of tested extracts. Phenolic content and antiradical activity of pecan shell extracts are significantly varied with cultivars and methods of extraction.