Comparative metabolomics analysis of Citrus medica var. sarcodactylis Swingle and Limonia acidissima Linn. Fruits and leaves cultivated in Egypt in context to their antiviral effects.

A comprehensive study of fruits and leaves extracts of Citrus medica var. sarcodactylis Swingle and Limonia acidissima L. family Rutaceae was accomplished to investigate their antiviral activity along with their zinc oxide nanoparticles formulation (ZnONPs) against the avian influenza H5N1 virus. A thorough comparative phytochemical investigation of C. medica and L.acidissima leaves and fruits was performed using UPLC-QTOF-MS-MS. Antiviral effects further aided by molecular docking proved the highly significant potential of using C. medica and L.acidissima extracts as medicinal agents. Antiviral potency is ascendingly arranged as L. acidissima leaves (LAL) > L. acidissima fruits (LAF) > C. medica leaves (CML) at 160 µg. Nano formulation of LAF has the most splendid antiviral upshot. The metabolomic profiling of CMF and LAL revealed the detection of 48 & 74 chromatographic peaks respectively. Docking simulation against five essential proteins in survival and replication of the influenza virus revealed that flavonoid di-glycosides (hesperidin, kaempferol-3-O-rutinoside, and kaempferol-7-neohesperidoside) have shown great affinity toward the five investigated proteins and achieved docking scores which approached or even exceeded that achieved by the native ligands. Hesperidin has demonstrated the best binding affinity toward neuraminidase (NA), haemagglutinin (HA), and polymerase protein PB2 (-10.675, -8.131, and -10.046 kcal/mol respectively. We propose using prepared crude methanol extracts of both plants as an antiviral agent.

Bio-fabricated zinc oxide nanoparticles mediated by endophytic fungus Aspergillus sp. SA17 with antimicrobial and anticancer activities: in vitro supported by in silico studies.

Introduction: In recent years, the world's attention has been drawn to antimicrobial resistance (AMR) because to the frightening prospect of growing death rates. Nanomaterials are being investigated due to their potential in a wide range of technical and biological applications. Methods: The purpose of this study was to biosynthesis zinc oxide nanoparticles (ZnONPs) using Aspergillus sp. SA17 fungal extract, followed by characterization of the produced nanoparticles (NP) using electron microscopy (TEM and SEM), UV-analysis, X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR). Results and Discussion: The HR-TEM revealed spherical nanoparticles with an average size of 7.2 nm, and XRD validated the crystalline nature and crystal structure features of the generated ZnONPs, while the zeta potential was 18.16 mV, indicating that the particles' surfaces are positively charged. The FT-IR was also used to identify the biomolecules involved in the synthesis of ZnONPs. The antibacterial and anticancer properties of both the crude fungal extract and its nano-form against several microbial strains and cancer cell lines were also investigated. Inhibition zone diameters against pathogenic bacteria ranged from 3 to 13 mm, while IC50 values against cancer cell lines ranged from 17.65 to 84.55 M. Additionally, 33 compounds, including flavonoids, phenolic acids, coumarins, organic acids, anthraquinones, and lignans, were discovered through chemical profiling of the extract using UPLC-QTOF-MS/MS. Some molecules, such pomiferin and glabrol, may be useful for antibacterial purposes, according to in silico study, while daidzein 4'-sulfate showed promise as an anti-cancer metabolite.

Green synthesis of zinc oxide nanoparticles using ethanolic extract of Gliricidia sepium (Jacq.) kunth. Ex. Walp., stem: Characterizations and their gastroprotective effect on ethanol-induced gastritis in rats.

The study presents a significant advancement in drug delivery and therapeutic efficacy through the successful synthesis of Gliricidia sepium(Jacq.) Kunth. ex. Walp., stem zinc oxide nanoparticles(GSS ZnONPs). The phenolic compounds present in Gliricidia sepium stem (GSS) particularly vanillic acid, apegnin-7-O-glucoside, syringic acid, and p-coumaric acid which were identified by HPLC. These compounds shown antioxidant and anti-inflammatory properties. GSS ZnONPs demonstrate pronounced gastroprotective effects against ethanol-induced gastritis, evidenced by the reduction in gastric lesions and mucosal injury upon its treatment. Histopathological evaluation and immunohistochemical analysis of nuclear factor erythroid 2-related factor 2 (Nrf2) expression further validate these results, revealing the amelioration of ethanol-induced gastritis and improved gastric tissue condition due to their treatment. Noteworthy is the dose-dependent response of GSS ZnONPs, showcasing their efficacy even at lower doses against ethanol-induced gastritis which is confirmed by different biomarkers. These findings have substantial implications for mitigating dosage-related adverse effects while preserving therapeutic benefits, offering a more favorable treatment approach. This study aims to investigate the potential gastroprotective activity of GSS ZnONPs against gastritis.

Citrus clementine Peel Essential Oil Ameliorates Potassium Dichromate-Induced Lung Injury: Insights into the PI3K/AKT Pathway.

Acute Lung Injury (ALI) is a life-threatening syndrome that has been identified as a potential complication of COVID-19. There is a critical need to shed light on the underlying mechanistic pathways and explore novel therapeutic strategies. This study aimed to examine the potential therapeutic effects of Citrus clementine essential oil (CCEO) in treating potassium dichromate (PDC)-induced ALI. The chemical profile of CCEO was created through GC-MS analysis. An in vivo study in rats was conducted to evaluate the effect of CCEO administrated via two different delivery systems (oral/inhalation) in mitigating acute lung injury (ALI) induced by intranasal instillation of PDC. Eight volatile compounds were identified, with monoterpene hydrocarbons accounting for 97.03% of the identified constituents, including 88.84% of D-limonene. CCEO at doses of 100 and 200 mg/kg bw exhibited antioxidant and anti-inflammatory properties. These significant antioxidant properties were revealed through the reduction of malondialdehyde (MDA) and the restoration of reduced glutathione (GSH). In addition, inflammation reduction was observed by decreasing levels of cytokines tumor necrosis factor-α and tumor growth factor-ß (TNF-α and TGF-ß), along with an increase in phosphatidylinositide-3-kinase (PI3K) and Akt overexpression in lung tissue homogenate, in both oral and inhalation routes, compared to the PDC-induced group. These results were supported by histopathological studies and immunohistochemical assessment of TGF-ß levels in lung tissues. These findings revealed that CCEO plays an integral role in relieving ALI induced by intranasal PDC and suggests it as a promising remedy.

Phytochemical Profiling and Antiviral Activity of Green Sustainable Nanoparticles Derived from Maesa indica (Roxb.) Sweet against Human Coronavirus 229E.

Plant secondary metabolites are key components for new, safe and effective drugs. Ethanolic extract of Maesa indica Roxb. Sweet (ME) aerial parts were used for biosynthesis of sustainable green zinc oxide nanoparticles (ZnO NPs) with an average particle size 6.80 ± 1.47 nm and zeta potential -19.7 mV. Both transmission electron microscopy and X-ray diffraction assay confirmed the hexagonal shape of ZnO NPs. Phenolic ingredients in ME were identified using LC-ESI-MS/MS-MRM revealing the identification of chlorogenic acid, gallic acid, caffeic acid, rutin, coumaric acid, vanillin, naringenin, quercetin, ellagic acid, 3.4-dihydroxybenzoic acid, methyl gallate, kaempferol, ferulic acid, syringic acid, and luteolin. The major compound was chlorogenic acid at concentration of 1803.84 µg/g. The antiviral activity of ME, ZnO NPs, and combination of ME with ZnO NPs against coronavirus 229E were investigated. ZnO NPs had superior antiviral effect against coronavirus 229E than ME while their combination showed the highest anti-coronavirus 229E effect, with 50% inhibition concentration (IC50) of 5.23 ± 0.18 µg/mL and 50% cytotoxic concentration (CC50) of 138.49 ± 0.26 µg/mL while the selectivity index (SI) was 26.47. The current study highlighted the possible novel anti-coronavirus 229E activity of green ZnO NPs synthesized from Maesa indica. More studies are needed to further investigate this antiviral activity to be utilized in future biomedical and environmental applications.

Characterization and Isolation of the Major Biologically Active Metabolites Isolated from Ficus retusa and Their Synergistic Effect with Tetracycline against Certain Pathogenic-Resistant Bacteria.

Globally, pathogenic microbes have reached a worrisome level of antibiotic resistance. Our work aims to identify and isolate the active components from the bioactive Ficus retusa bark extract and assess the potential synergistic activity of the most major compounds' constituents with the antibiotic tetracycline against certain pathogenic bacterial strains. The phytochemical screening of an acetone extract of F. retusa bark using column chromatography led to the identification of 10 phenolic components. The synergistic interaction of catechin and chlorogenic acid as the most major compounds with tetracycline was evaluated by checkerboard assay followed by time-kill assay, against Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, and Salmonella typhi with fraction inhibitory concentration index values (FICI) of 0.38, 0.43, 0.38, 0.38, 0.38, and 0.75 for catechin and 0.38, 0.65, 0.38, 0.63, 0.38, and 0.75 for chlorogenic acid. The combination of catechin and chlorogenic acid with tetracycline significantly enhanced antibacterial action against gram-positive and gram-negative microorganisms; therefore, catechin and chlorogenic acid combinations with tetracycline could be employed as innovative and safe antibiotics to combat microbial resistance.

The Biosynthesized Zinc Oxide Nanoparticles' Antiviral Activity in Combination with Pelargonium zonale Extract against the Human Corona 229E Virus.

Almost one-third of all infectious diseases are caused by viruses, and these diseases account for nearly 20% of all deaths globally. It is becoming increasingly clear that highly contagious viral infections pose a significant threat to global health and economy around the world. The need for innovative, affordable, and safe antiviral therapies is a must. Zinc oxide nanoparticles are novel materials of low toxicity and low cost and are known for their antiviral activity. The genus Pelargonium was previously reported for its antiviral and antimicrobial activity. In this work, Pelargonium zonale leaf extract chemical profile was studied via high-performance liquid chromatography (HPLC) and was used for the biosynthesis of zinc oxide nanoparticles. Furthermore, the antiviral activity of the combination of P. zonale extract and the biosynthesized nanoparticles of ZnO against the human corona 229E virus was investigated. Results revealed that ZnONPs had been biosynthesized with an average particle size of about 5.5 nm and characterized with UV, FTIR, TEM, XRD, and SEM. The antiviral activity showed significant activity and differences among the tested samples in favor of the combination of P. zonale extract and ZnONPs (ZnONPs/Ex). The lowest IC50, 2.028 µg/mL, and the highest SI, 68.4 of ZnONPs/Ex, assert the highest antiviral activity of the combination against human coronavirus (229E).

Pharmacological and metabolomic profiles of Musa acuminata wastes as a new potential source of anti-ulcerative colitis agents.

Musa acuminata (MA) is a popular fruit peels in the world. Non-food parts of the plant have been investigated for their antioxidant and anti-ulcerative colitis activity. Metabolomic approaches were found to be informative as a screening tool. It discovered different metabolites depending on statistical analysis. The antioxidant activity content was measured by colorimetric method. Seventy six investigated metabolites were observed. The identities of some of these markers were confirmed based on their MS2 fragmentation and NMR spectroscopy. These include: cinnamic acid and its dimer 2-hydroxy-4-(4-methoxyphenyl)-1H-phenalen-1-one beside; gallic acid and flavonoids; quercetin, quercetin-3-O-ß-D-glucoside, luteolin-7-O-ß-D-glucopyranoside. GC/MS analysis of MA peels essential oil led to identification of 37 compounds. The leaves, pseudostem and fruit peels extracts were tested for their safety and their anti-ulcerative colitis efficacy in rats. Rats were classified into: normal, positive, prednisolone reference group, MA extracts pretreated groups (250-500 mg/kg) for 2 weeks followed by induction of ulcerative colitis by per-rectal infusion of 8% acetic acid. Macroscopic and microscopic examinations were done. Inflammatory markers (ANCA, CRP and Ilß6) were measured in sera. The butanol extracts showed good antioxidant and anti-inflammatory activities as they ameliorated macroscopic and microscopic signs of ulcerative colitis and lowered the inflammatory markers compared to untreated group. MA wastes can be a potential source of bioactive metabolites for industrial use and future employment as promising anti-ulcerative colitis food supplements.

Phytochemical Profiling of the Leaf Extract of Ximenia americana var. caffra and Its Antioxidant, Antibacterial, and Antiaging Activities In Vitro and in Caenorhabditis elegans: A Cosmeceutical and Dermatological Approach.

We previously annotated the phytochemical constituents of a root extract from Ximenia americana var. caffra and highlighted its hepatoprotective and hypoglycemic properties. We here extended our study on the leaf extract and identified its phytoconstituents using HPLC-PDA-ESI-MS/MS. In addition, we explored its antioxidant, antibacterial, and antiaging activities in vitro and in an animal model, Caenorhabditis elegans. Results from HPLC-PDA-ESI-MS/MS confirmed that the leaves contain 23 secondary metabolites consisting of condensed tannins, flavonol glycosides, flavone glycosides, and flavonol diglycosides. The leaf extract demonstrated significant antioxidant activity in vitro with IC50 value of 5 µg/mL in the DPPH assay and 18.32 µg/mL in the FRAP assay. It also inhibited four enzymes (collagenase, elastase, hyaluronidase, and tyrosinase) crucially involved in skin remodeling and aging processes with comparable activities to reference drugs along with four pure secondary metabolites identified from the extract. In accordance with the in vitro result, in vivo tests using two transgenic strains of C. elegans demonstrated its ability to reverse oxidative stress. Evidence included an increased survival rate in nematodes treated with the prooxidant juglone to 68.9% compared to the 24.8% in untreated worms and a reduced accumulation of intracellular reactive oxygen species (ROS) in a dose-dependent manner to 77.8%. The leaf extract also reduced levels of the expression of HSP 16.2 in a dose-dependent manner to 86.4%. Nuclear localization of the transcription factor DAF-16 was up to 10 times higher in worms treated with the leaf extract than in the untreated worms. The extract also inhibited the biofilm formation of Pseudomonas aeruginosa (a pathogen in skin infections) and reduced the swimming and swarming mobilities in a dose-dependent fashion. In conclusion, leaves of X. americana are a promising candidate for preventing oxidative stress-induced conditions, including skin aging.

Green Synthesized Zinc Oxide Nanoparticles Based on Cestrum diurnum L. of Potential Antiviral Activity against Human Corona 229-E Virus.

SARS-CoV-2 has caused more than 596 million infections and 6 million fatalities globally. Looking for urgent medication for prevention, treatment, and rehabilitation is obligatory. Plant extracts and green synthesized nanoparticles have numerous biological activities, including antiviral activity. HPLC analysis of C. dirnum L. leaf extract showed that catechin, ferulic acid, chlorogenic acid, and syringic acid were the most major compounds, with concentrations of 1425.16, 1004.68, 207.46, and 158.95 µg/g, respectively. Zinc nanoparticles were biosynthesized using zinc acetate and C. dirnum extract. TEM analysis revealed that the particle size of ZnO-NPs varied between 3.406 and 4.857 nm. An XRD study showed the existence of hexagonal crystals of ZnO-NPs with an average size of 12.11 nm. Both ZnO-NPs (IC50 = 7.01 and CC50 = 145.77) and C. dirnum L. extract (IC50 = 61.15 and CC50 = 145.87 µg/mL) showed antiviral activity against HCOV-229E, but their combination (IC50 = 2.41 and CC50 = 179.23) showed higher activity than both. Molecular docking was used to investigate the affinity of some metabolites against the HCOV-229E main protease. Chlorogenic acid, solanidine, and catchin showed high affinity (-7.13, -6.95, and -6.52), compared to the ligand MDP (-5.66 Kcal/mol). Cestrum dinurum extract and ZnO-NPs combination should be subjected to further studies to be used as an antiviral drug.

The role of active metabolites isolated from Jasminum multiflorum flowers against hepatitis C virus infection and related hepatocellular carcinoma.

Jasminum multiflorum Burm. f. (J. multiflorum) is an ornamental plant with traditional medicinal importance. This study aims to evaluate the activity of J. multiflorum isolated compounds against hepatocellular carcinoma cells infected with hepatitis C virus (HCV) in vitro. The in vitro anti-viral and anti-oncogenic-related activity were validated by anchorage-independent assay plus transwell migration/invasion and spreading assay. In addition to chromatographic isolation of the active metabolites. The flower extract demonstrated a significant antiviral potential through reducing active viral replication by more than 90%. Study results credit this to specific reduction of viral NS5A and cellular EphA2 protein levels. Molecular docking analysis proved the role of the isolated compounds especially multifloroside, jasfloroside A and jasfloroside B as possible anti HCV molecules.

Antiviral Activity of Zinc Oxide Nanoparticles Mediated by Plumbago indica L. Extract Against Herpes Simplex Virus Type 1 (HSV-1).

INTRODUCTION: Plumbago indica L. is considered a valuable source in the Plumbaginaceae family for various types of active compound such as alkaloids, phenolics and saponins. To promote the usage of P. indica in the bionanotechnology field, zinc oxide nanoparticles (ZnONPs) were biosynthesized by using its alcoholic extract. The inhibitory effects of ZnONPs and the plant extract were also evaluated against HSV-1. METHODS: ZnONPs were described by the following techniques, UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), zeta potential, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and x-ray diffraction (XRD). The phenolic and flavonoid contents of P. indica extract, which are accountable for bioreduction, formation and stabilization of the nanoparticles, were analyzed by HPLC technique. The antiviral assessment was implemented on both agents by using Vero cell lines. RESULTS: DLS revealed that the average size of ZnONPs was 32.58 ± 7.98 nm and the zeta potential was -20.8 mV. The observation of TEM analysis revealed that the particle size of ZnONPs varied from 2.56 to 8.83 nm. The XRD analysis verified the existence of pure crystals of hexagonal shapes of nanoparticles of ZnO with a main average size of 35.28 nm that is approximating to the values of particle size acquired by SEM analysis (19.64 and 23.21 nm). The HPLC analysis of P. indica ethanolic extract showed that gallic acid, chlorogenic acid and rutin were the major compounds, with concentrations equal to 8203.99, 2965.95 and 1144.99 µg/g, respectively. Regarding the antiviral assessment, the synthesized uncalcinated ZnONPs were found to exhibit a promising activity against HSV-1, with CC50 and IC50 values equal to 43.96 ± 1.39 and 23.17 ± 2.29 µg/mL, respectively. CONCLUSION: The green synthesized ZnONPs are considered promising adjuvants to enhance the efficacy of HSV-1 drugs.

Nano Zinc Oxide Green-Synthesized from Plumbago auriculata Lam. Alcoholic Extract.

Zinc oxide nanoparticles (ZnO NPs) were synthesized by using an alcoholic extract of the flowering aerial parts of Plumbago auriculata Lam. Dynamic Light Scattering (DLS) revealed that the average size of synthesized ZnO NPs was 10.58 ± 3.350 nm and the zeta potential was -19.6 mV. Transmission electron microscopy (TEM) revealed that the particle size was in the range from 5.08 to 6.56 nm. X-ray diffraction (XRD) analysis verified the existence of pure hexagonal shaped crystals of ZnO nanoparticles with an average size of 35.34 nm in the sample, which is similar to the particle size analysis acquired by scanning electron microscopy (SEM) (38.29 ± 6.88 nm). HPLC analysis of the phenolic ingredients present in the plant extract showed that gallic acid, chlorogenic acid, and catechin were found as major compounds at concentrations of 1720.26, 1600.42, and 840.20 µg/g, respectively. Furthermore, the inhibitory effects of ZnO NPs and the plant extract against avian metapneumovirus (aMPV) subtype B were also investigated. This assessment revealed that the uncalcinated form of Nano-ZnO mediated by P. auriculata Lam. extract possessed a significant antiviral activity with 50% cytotoxic concentration (CC50) and 50% inhibition concentration (IC50) of 52.48 ± 1.57 and 42.67 ± 4.08 µg/mL, respectively, while the inhibition percentage (IP) was 99% and the selectivity index (SI) was 1.23.

Pea (Pisum sativum) peel extract attenuates DOX-induced oxidative myocardial injury.

The goal of this work aimed to evaluate the protective effects of pea (Pisum sativum) peels extract versus doxorubicin-induced oxidative myocardial injury in male mice. The mice were divided into seven groups (n = 7): (I) control group; (II) P. sativum 250 group; (III) P. sativum 500 group; (IV) DOX (3 times alternately of 2.5 mg/kg/week, i.p. for a continuous two-week period) group; (V) Vit. E 100 + DOX group; (VI) P. sativum 250 + DOX group, and (VII) P. sativum 500 + DOX group). Twenty polyphenolic compounds, mainly flavonoid glycosides such as quercetin, kaempferol apigenin, and phenolics compounds were characterized by LC-MS/MS analysis in the examined extract. DOX administration elevated the activities of serum biomarkers of myocardial dysfunction (ALT, AST, ALP, LDH, troponin, CPK, and CK-MB), lipid profile, and proinflammatory cytokines. Also, it decreased cardiac antioxidants (GSH, SOD, GPX, CAT) and increased myocardial markers of oxidative stress (NO and MDA) and inflammatory marker (MPO). As well as it downregulated and upregulated the Bcl-2 (anti-apoptotic gene) and the Bax (pro-apoptotic gene) expressions, respectively. Pre-treatment of DOX-exposed mice with P. sativum or vitamin E (as a reference protective antioxidant) alleviated the changes dose-dependently via DOX-induced cardiotoxicity. These data show that P. sativum has a cardio-protective impact against DOX-induced cardiomyocyte damage in mice via boosting endogenous antioxidants, decreasing inflammation, and regulating BcL-2 and Bax apoptosis pathway, which might be related to the presence of flavonoid glycosides. P. sativum peels are a by-product that could be suggested for further screening as a possible new candidate for therapeutic use.

Antioxidant, Anti-Inflammatory and Cytotoxic Activities of Jasminum multiflorum (Burm. F.) Andrews Leaves towards MCF-7 Breast Cancer and HCT 116 Colorectal Cell Lines and Identification of Bioactive Metabolites.

BACKGROUND: The plants of high phenolic contents are perfect antioxidant and anti-inflammatory agents and participate in biological studies as effective agents towards different cancer cell lines. OBJECTIVE: To investigate the antioxidant, anti-inflammatory, and cytotoxic activities of the hydromethanolic leaf extract of Jasminum multiflorum (Burm. f.) Andrews. (J. multiflorum), and phenolic profiling of the extract. METHODS: The antioxidant activity for the extract was estimated using ß-Carotene-linoleic and Ferric Reducing Antioxidant Power (FRAP) assays. The anti-inflammatory activity was evaluated by histamine release assay. Cytotoxicity of J. multiflorum was performed using a neutral red uptake assay towards breast cancer (MCF-7) and colorectal cancer (HCT 116) cell lines. Phenolic profiling of the leaves was characterized using high performance liquid chromatography coupled to photodiode array detector-mass spectroscopy-mass spectroscopy (HPLC-PDA-MS/MS), and chromatographic isolation and identification of the isolated compounds were performed using spectroscopic and NMR data, and virtual docking was performed to the isolated compounds against HSP90 (HEAT SHOCK PROTEIN 90). RESULTS: At a concentration of 75 µg mL-1, J. multiflorum extract showed high antioxidant power; 68.23±0.35 % inhibition and 60.30±0.60 a TEAC (µmol Trolox g-1) for ß-Carotene-linoleic assay and FRAP assay; respectively, and possessed anti-inflammatory activity with IC50 67.2 µg/ml. J. multiflorum showed high cytotoxic activity with IC50 of 24.81 µg/ml and 11.38 µg/ml for MCF-7 and HCT 116 cell lines, respectively. HPLC-PDA-MS/MS analysis tentatively identified 39 compounds; major compounds are secoiridoid glycosides, kaempferol, and quercetin glycosides, in addition to simple phenylethanoid compounds. Isolation of active metabolites was performed and led to the isolation and identification of four compounds. On the basis of docking study using HSP90 legend, kaempferol neohesperidoside showed a high cytotoxic potential supported by a high affinity score towards HSP90 legend protein. CONCLUSION: Jasminum multiflorum is a good candidate to isolate cytotoxic agents.

Anti-Inflammatory, Antipyretic, and Analgesic Properties of Potamogeton perfoliatus Extract: In Vitro and In Vivo Study.

Natural antioxidants, especially those of plant origins, have shown a plethora of biological activities with substantial economic value, as they can be extracted from agro-wastes and/or under exploited plant species. The perennial hydrophyte, Potamogeton perfoliatus, has been used traditionally to treat several health disorders; however, little is known about its biological and its medicinal effects. Here, we used an integrated in vitro and in vivo framework to examine the potential effect of P. perfoliatus on oxidative stress, nociception, inflammatory models, and brewer's yeast-induced pyrexia in mice. Our results suggested a consistent in vitro inhibition of three enzymes, namely 5-lipoxygenase, cyclooxygenases 1 and 2 (COX-1 and COX-2), as well as a potent antioxidant effect. These results were confirmed in vivo where the studied extract attenuated carrageenan-induced paw edema, carrageenan-induced leukocyte migration into the peritoneal cavity by 25, 44 and 64% at 200, 400 and 600 mg/kg, p.o., respectively. Moreover, the extract decreased acetic acid-induced vascular permeability by 45% at 600 mg/kg, p.o., and chemical hyperalgesia in mice by 86% by 400 mg/kg, p.o., in acetic acid-induced writhing assay. The extract (400 mg/kg) showed a longer response latency at the 3 h time point (2.5 fold of the control) similar to the nalbuphine, the standard opioid analgesic. Additionally, pronounced antipyretic effects were observed at 600 mg/kg, comparable to paracetamol. Using LC-MS/MS, we identified 15 secondary metabolites that most likely contributed to the obtained biological activities. Altogether, our findings indicate that P. perfoliatus has anti-inflammatory, antioxidant, analgesic and antipyretic effects, thus supporting its traditional use and promoting its valorization as a potential candidate in treating oxidative stress-associated diseases.

Syzygium jambos extract mitigates pancreatic oxidative stress, inflammation and apoptosis and modulates hepatic IRS-2/AKT/GLUT4 signaling pathway in streptozotocin-induced diabetic rats.

The protective effect of Syzygium jambos (SJ) bark extract against streptozotocin-induced diabetes was tested in rats. Animals were treated with 100 or 200 mg/kg of the extract or glibenclamide, 0.5 mg/kg per os, once daily: started 2 days before streptozotocin (STZ) injection and lasted for 14 days after STZ injection. The effect of the extract was also evaluated on normal rats in comparison with glibenclamide. Diabetic animals showed an elevated blood glucose level, positive glycosuria, elevated fructosamine, pancreatic malondialdehyde, pancreatic TNF-a, and pancreatic caspase-3 levels and decreased serum insulin, pancreatic IL-10, pancreatic BCL-2, reduced glutathione (GSH), liver insulin substrate-2, liver phosphorylated protein kinase B (p-AKT) and liver glucose transporter 4 (GLUT4) levels. Histopathological examination of diabetic rats revealed islets destruction and vacuolation and collagen fibers deposition. All these changes were mitigated dose dependently by the extract. The high dose of the extract exerted comparable effects with glibenclamide in most studied parameters. These results indicated the protective role of SJ against the STZ diabetogenic action. In the pancreatic and hepatic tissue of diabetic rats, SJ effectively recovered pancreatic cells by reducing hyperglycemia through activating endogenous antioxidants, dynamic insulin production, and suppressing inflammation and apoptosis. The observed results might be attributed to the existence of 10 secondary metabolites as annotated by LC-MS. Taken together, S. jambos is a potential candidate for further studies to confirm its activities as a therapeutic agent for diabetic patients.

A Leaf Extract of Harrisonia abyssinica Ameliorates Neurobehavioral, Histological and Biochemical Changes in the Hippocampus of Rats with Aluminum Chloride-Induced Alzheimer's Disease.

Aluminum (Al) is an omnipresent mineral element in the environment. The brain is a central target of Al toxicity, being highly susceptible to oxidative damage. Therefore, recognition of drugs or natural products that guard against Al-mediated neuronal cell death is a powerful strategy for prevention and treatment of neurodegenerative disorders. This work aimed to explore the potential of a leaf extract from Harrisonia abyssinica to modulate the neurobehavioral, biochemical and histopathological activities induced experimentally by Al in vivo. Rats subjected to Al treatment displayed a reduction in learning and memory performance in a passive avoidance test accompanied by a decrease in the hippocampal monoamine and glutamate levels in addition to suppression of Bcl2 expression. Moreover, malondialdehyde (MDA), inflammatory markers (TNF-α, IL-1ß), apoptotic markers (caspase-3 and expression of Bax) and extracellular regulated kinase (ERK1/2) levels were elevated along with acetylcholinesterase (AChE) activity, histological changes and marked deposition of amyloid ß plaques in the hippocampus region of the brain tissues being observed in Al-treated animals. Concomitant administration of the high dose of H. abyssinica (200 mg/kg b.w.) restored nearly normal levels of all parameters measured, rather than the low dose (100 mg/kg b.w.), an effect that was comparable to the reference drug (rivastigmine). Molecular docking revealed the appropriate potential of the extract components to block the active site of AChE and ERK2. In conclusion, H. abyssinica leaf extract conferred neuroprotection against Al-induced neurotoxic effects, most likely due to its high phenolic and flavonoid content.

A sulfated polyphenols-rich extract from Sabal yapa exhibits antitumor activities in Ehrlich ascites carcinoma.

Cancer is the second leading cause of mortality accounting for one in every six deaths globally. Plant secondary metabolites, among them polyphenols, represent an effective and much safer alternative approach to the currently available medications. In this work, utilizing LC-MS/MS, we characterized the constituents of S. yapa leaves extract and evaluated its antioxidant and anticancer properties. In total, 34 secondary metabolites, mainly flavonoids (Tricin, luteolin, and apigenin and their glucosides as well as sulfated derivatives) were identified. The extract manifested substantial antioxidant activity in DPPH assay, and high total phenolic content determined by Folin Ciocalteu method. The extract was safe up to 4800 mg/kg b.wt. when administered orally in mice and neither affected the hematological parameters nor the liver enzyme levels at the studied dose (LD50, 480 mg, kg b.wt.). In the treated animals, the extract surpassed the reference drug (5-flouro uracil) and significantly reduced the tumor volume and weight by 71.50 and 85.46%, respectively, increased the median survival time to 53.2 days and the lifespan by 116%. The extract improved all the hematological parameters, where it increased the hemoglobin (Hb) concentration, red blood cell (RBC) count, packed cell volume (PVC) and platelets by 58.21, 8.98, 9.89 and 120%, respectively, compared to the untreated EAC bearing animals. Additionally, the extract significantly declined the elevated levels of ALT and AST enzymes by 29.18% and 59.88%, respectively. In molecular docking, the annotated flavonoids displayed appreciable binding affinities to the active sites of VEGFR1 and VEGFR2. In conclusion, Saba yapa is a promising plant that can be introduced to further advanced clinical studies for the development of novel anticancer drugs with lower side effects.

Antiviral zinc oxide nanoparticles mediated by hesperidin and in silico comparison study between antiviral phenolics as anti-SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the coronavirus (COVID-19), is the virus responsible for over 69,613,607 million infections and over 1,582,966 deaths worldwide. All treatment measures and protocols were considered to be supportive only and not curative. During this current coronavirus pandemic, searching for pharmaceutical or traditional complementary and integrative medicine to assist with prevention, treatment, and recovery has been advantageous. These phytopharmaceuticals and nutraceuticals can be more economic, available, safe and lower side effects. This is in silico comparison study of ten phenolic antiviral agents against SARS-CoV-2, as well as isolation of the most active metabolite from natural sources. Zinc oxide nanoparticles (ZnO NPs) were also then prepared using these metabolite as a reducing agent. All tested compounds showed predicted anti-SARS-CoV-2 activity. Hesperidin showed the highest docking score, this leads us to isolate it from the orange peels and we confirmed its structure by conventenional spectroscopic analysis. In addition, synthesis of hesperidin zinc oxide nanoparticles was characterized by UV, IR, XRD and TEM. In vitro antiviral activity of hesperidin and ZnO NPs was evaluated against hepatitis A virus as an example of RNA viruses. However, ZnO NPs and hesperidin showed antiviral activity against HAV but ZnO NPs showed higher activity than hesperidin. Thus, hesperidin and its mediated ZnO nanoparticles are willing antiviral agents and further studies against SARS-CoV-2 are required to be used as a potential treatment.