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Mina Michael Melk,1 Seham S El-Hawary,1 Farouk Rasmy Melek,2 Dalia Osama Saleh,3 Omar M Ali,4 Mohamed A El Raey,5 Nabil Mohamed Selim1 1Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Giza, Egypt; 2Chemistry of Natural Compounds Department, National Research Centre, Giza, Egypt; 3Pharmacology Department, National Research Centre, Giza, Egypt; 4Department of Chemistry, Turabah University College, Turabah Branch, Taif University, Taif, 21944, Saudi Arabia; 5Department of Phytochemistry and Plant Systematics, Pharmaceutical Division, National Research Centre, Dokki, Cairo, EgyptCorrespondence: Nabil Mohamed Selim; Omar M Ali Email nabil.selim@pharma.cu.edu.eg; om.ali@tu.edu.saIntroduction: 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.Keywords: ZnO nanoparticles, Plumbago indica L., HPLC analysis, antiviral activity and green synthesis

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

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 IC 50 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Abdelrahman, El Hawary, Mohsen, El Raey, Selim, Hamdan, Ghareeb and Hamed.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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-β (TNF-α and TGF-β), 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-β 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.

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 (IC 50 ) of 5.23 ± 0.18 µg/mL and 50% cytotoxic concentration (CC 50 ) 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.

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 (IC 50 = 7.01 and CC 50 = 145.77) and C. dirnum L. extract (IC 50 = 61.15 and CC 50 = 145.87 µg/mL) showed antiviral activity against HCOV-229E, but their combination (IC 50 = 2.41 and CC 50 = 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.

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 IC 50, 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).

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.

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 MS 2 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-β-D-glucoside, luteolin-7-O-β-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 Ilβ6) 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., (© 2022. The Author(s).)

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.

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 IC 50 value of 5  μ g/mL in the DPPH assay and 18.32  μ g/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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Widad Ben Bakrim et al.)

Sciatic nerve injury is often associated with neuropathic pain and neuroinflammation in the central and peripheral nervous systems. In our previous work, Potamogeton perfoliatus L. displayed anti-inflammatory, antipyretic and analgesic properties, predominantly via the inhibition of COX-2 enzyme and attenuation of oxidative stress. Herein, we extended our investigations to study the effects of the plant's extract on pain-related behaviors, oxidative stress, apoptosis markers, GFAP, CD68 and neuro-inflammation in sciatic nerve chronic constriction injury (CCI) rat model. The levels of the pro-inflammatory marker proteins in sciatic nerve and brainstem were measured with ELISA 14 days after CCI induction. Pretreatment with the extract significantly attenuated mechanical and cold allodynia and heat hyperalgesia with better potential than the reference drug, pregabalin. In addition, CCI lead to the overexpression of prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), tumor necrosis alpha (TNFα), nuclear factor κB (NF-κB), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and NADPH oxidase-1 (NOX-1) and decreased the catalase level in sciatic nerve and brainstem. The observed neuro-inflammatory changes were accompanied with glial cells activation (increased GFAP and CD68 positive cells), apoptosis (increased Bax) and structural changes in both brainstem and sciatic nerve. The studied extract attenuated the CCI-induced neuro-inflammatory changes, oxidative stress, and apoptosis while it induced the expression of Bcl-2 and catalase in a dose dependent manner. It also decreased the brainstem expression of CD68 and GFAP indicating a possible neuroprotection effect. Taking together, P. perfoliatus may be considered as a novel therapy for neuropathic pain patients after performing the required clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mahmoud, Rezq, Alsemeh, Abdelfattah, El-Shazly, Daoud, El Raey and Sobeh.)

In this study chemical profiling of Jasminum azoricum L. ( J. azoricum ) using HPLC-PDA/MS/MS and evaluation of its in-vitro cytotoxicity towards the human breast cancer cell line (MCF-7), human colorectal cancer cell (HCT-116) and human hepatocellular carcinoma (Huh-7) cell lines. The viability % was determined by the neutral red uptake assay. The study led to the identification of 37 secondary metabolite; major nine compounds were subjected to virtual docking to determine their role in tumour growth inhibition by controlling apoptosis and cancer cell proliferation using the 3D crystal structure of MST3 ligand protein. Two compounds; sambacoside A and molihauside C, showed high-affinity values of (-9.91, -9.57) kcal/mol against MST3 protein . In silico prediction of absorption, distribution, metabolism, excretion and toxicity (ADMET) was performed and revealed no mutagenicity, no tumorigenicity and non-irritant actions of both compounds, so J. azoricum could be used as a beneficial source for cytotoxic compounds.[Figure: see text].

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 (CC 50 ) and 50% inhibition concentration (IC 50 ) 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.

This study focused on the profiling of phenolic constituents in 80% methanolic extracts of the leaves of some Jasminum species cultivated in Egypt and their antioxidant activities. Phenolic profiling was performed by total phenolic contents, total flavonoid contents and HPLC-DAD for selected species in comparison to authentic standards. DPPH assay was used to estimate the antioxidant activities of Jasminum azoricum L. , Jasminum humile L. , Jasminum multiflorum (Burm.f.) Andrew , Jasminum officinale L. , Jasminum sambac (Ait) L. "Arabian Nights cultivar" and Jasminum sambac (Ait) L. "Grand Duke of Tuscany cultivar". Jasminum multiflorum showed the highest antioxidant activity among selected species with IC 50 of 34.8 µg/ml. J. multiflorum showed high concentrations of hydroxytyrosol, protocatechuic acid, hydroxybenzoic acid, kaempferol- 3-O- neohesperidoside, and quercetin- 3-O -glucoside with concentrations of 977.1 µg/g, 2224.7 µg/g, 714.8 µg/g, 1738.8 µg/g, and 4356.1 µg/g, respectively.

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., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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.

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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-1β), 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 β 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.

Nowadays, the biosynthesis of metal nanoparticles, particularly from plants, has been gaining interest. In the present work, the methanolic extracts of leaves, fruits, and the pollen grains of Sabal blackburniana were used for the green synthesis of ZnO nanoparticles, which were early detected by the formation of precipitate and further confirmed by UV-vis spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infra-red (FT-IR) spectroscopy and zeta potential (ZP) studies. TEM analysis has shown different shapes, predominantly irregular small spherical narrow particles included in hexagonal structures with size ranging from 2.23 to 49.56 nm. The XRD pattern confirmed that all synthesized ZnO nanoparticles have wurtzite hexagonal structure with crystalline nature. The average particle crystallite sizes were 47.21, 47.67 and 47.8 nm. The UV-visible spectra showed λ max in the range of 354-368 nm, which indicated the presence of ZnO nanoparticles. The FT-IR analysis identifies the characteristic functional groups present on the surface of ZnO nanoparticles. The ZP determination demonstrated that all representative selected synthesized ZnONPs exhibited acceptable ZP values of -30.8 to -45.9 mV, which indicated their good stability. In addition, the anti-Alzheimer potential of the selected extracts and ZnONPs was evaluated by assessing acetylcholinesterase inhibitory activity in vitro according to the improved Ellman method. The results indicated that the selected extracts have acetylcholinesterase inhibitory activity, and highlighted the promising inhibitory potential of green-synthesized ZnONPs using pollen grains, fruits and leaves extracts; they exhibited a potent inhibitory effect with IC 50 values 63.78 ± 1.04651, 81.985 ± 3.075 and 117.95 ± 6.858 ng ml -1 respectively in comparison to donepezil as standard (IC 50 = 50.7 ± 5.769 ng ml -1 ). Dereplication analysis of the selected extracts was performed using LC-MS; metabolic profiling revealed the presence of 41 compounds belonging to various chemical classes: flavonoids, steroidal saponins, terpenoids, alkaloids, lignans, sterols and fatty acids. Docking these dereplicated metabolites against the human AChE showed that the non-glycosylated flavonoid class of compounds was able to achieve interesting binding modes inside the AChE active site; they are suggested to be associated with the observed anti-AChE activity of Sabal extracts. This study is the first report to shed light on the acetylcholinesterase inhibitory activity of green-synthesized ZnO nanoparticles of S. blackburniana metabolites., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

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 (LD 50 , 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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Infections associated with the emergence of multidrug resistance and mosquito-borne diseases have resulted in serious crises associated with high mortality and left behind a huge socioeconomic burden. The chemical investigation of Lavandula coronopifolia aerial parts extract using HPLC-MS/MS led to the tentative identification of 46 compounds belonging to phenolic acids, flavonoids and their glycosides, and biflavonoids. The extract displayed larvicidal activity against Culex pipiens larvae (LC 50 = 29.08 µg/mL at 72 h). It significantly inhibited cytochrome P-450 monooxygenase (CYP450), acetylcholinesterase (AChE), and carboxylesterase (CarE) enzymes with the comparable pattern to the control group, which could explain the mode of larvae toxification. The extract also inhibited the biofilm formation of Pseudomonas aeruginosa by 17-38% at different Minimum Inhibitory Concentrations (MICs) (0.5-0.125 mg/mL) while the activity was doubled when combined with ciprofloxacin (ratio = 1:1 v : v ). In conclusion, the wild plant, L. coronopifolia, can be considered a promising natural source against resistant bacteria and infectious carriers.

We have previously reported that the leaf extract of Albizia anthelmintica exhibited substantial antioxidant, anti-inflammatory, analgesic, and antipyretic properties in vivo. We also comprehensively characterized the active phytoconstituents and found several flavonoids and galloyl glucosides derivatives. In the current work, we explored the gastroprotective effects of the leaf extract in an indomethacin-induced ulcer model and the mechanisms involved. The rats being pretreated with the tested extract (100 and 200 mg kg -1 ) significantly prevented gastric lesions by 87.4% and 92.3%, respectively, and they had no structural derangements in the gastric mucosa. The extract significantly reduced the elevated levels of IKκB, NF-κB, TNF-α, IL-6, iNOS, and lipid peroxidation; increased the reduced level of glutathione peroxidase (GPx) activity; and reduced glutathione (GSH) in the indomethacin-induced ulcer model. The protective activities of the extract were similar in most aspects to those exerted by the known anti-ulcer drug famotidine. These activities might be attributed to the anti-inflammatory and antioxidant activities, and the reduction of iNOS levels. In conclusion, Albizia anthelmintica is a potential candidate for management of gastric ulcers with antioxidant properties.

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 β-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 β-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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

UPLC-MS/MS profiling of Cassia glauca leaves extract revealed the identification of 10 flavonoids. Kaempferol 3-O-β-D-rutinoside was isolated and studied for its cytotoxic activity. It showed high cytotoxic effects against MCF-7 (IC50 of 4.6±0.038 μg/ml) and HepG-2 (IC50 of 8.2±0.024 μg/ml) cancer cell lines, compared to the leaves extracts, their Ag nanoparticles, and doxorubicin. Moreover, Kaempferol 3-O-β-D-rutinoside exerted a synergistic cytotoxic effect with doxorubicin on MCF-7 cell lines. It was discovered as kinases and aldose reductase inhibitor while rationalizing its cytotoxic activity through molecular docking study. Thus, it is expected that the cardiotoxic effects of doxorubicin can be also decreased by using Kaempferol 3-O-β-D-rutinoside due to its aldose reductase inhibitory effect. These findings suggested that Kaempferol 3-O-β-D-rutinoside could be used in combination with chemotherapeutic drugs to increase the sensitivity to their cytotoxic activity and protect against their side effects., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Rhoifolin (Rho) exerts many biological activities such as anticancer, antidiabetic, hepatoprotective, antirheumatic, antibacterial, and antiviral properties. The neuroprotective action of this compound has not been studied. The goal of this study was to investigate the improvement impact of Rho on scopolamine (Sco)-induced zebrafish anxiety, amnesia, and brain oxidative stress and to elucidate the underlying mechanisms involved. Zebrafish were treated with Rho (1, 3, and 5 μg/L) for nine consecutive days and were subsequently subjected to Sco (100 μM) 30 min before behavioral tests (novel tank diving test, Y-maze, and novel object recognition tests). Rho was isolated from Chorisia crispiflora (Malvaceae) leaves and identified by different spectroscopic techniques. To further assess the possible mechanisms of Rho in enhancing the memory capacities in zebrafish, the in vivo antioxidant status and acetylcholinesterase (AChE) activity was also evaluated. Rho from Chorisia crispiflora leaves was identified. Rho could alleviate anxiety, memory deficits, and brain oxidative stress in Sco-treated zebrafish and could regulate the cholinergic function by inhibiting the AChE activity. Our results demonstrated that Rho could be a promising candidate compound against anxiety and amnesia by restoring the cholinergic activity and the amelioration of brain oxidative stress.

Leaves from Eugenia uniflora , the red Brazilian cherry, have a high content of flavonoids that possess several biological effects such as anti-inflammatory, antioxidant, and antidiabetic activities. However, their influence on carbon tetrachloride (CCl 4 )-induced acute liver injury in rats has not been investigated. In the current study, a bioguided fractionation assay revealed that the ethyl acetate fraction (EAF) of Eugenia uniflora is the safest and most active fraction. LC-MS analysis of the ethyl acetate fraction revealed 22 secondary metabolites, mainly myricetin and quercetin derivatives. EAF did not show toxicity up to 2000 mg/kg, and exhibited antioxidant activities in vitro in DPPH assay with IC 50 of 3.35 µg/mL. Additionally, EAF exhibited substantial antioxidant activities in vivo by counteracting the oxidative damage of the prooxidant juglone [80 µM] in Caenorhabditis elegans model organism and increased its survival rate in a dose-dependent fashion through the DAF-16/Foxo pathway. Furthermore, the hepatoprotective activity of EAF (200 mg/kg against carbon tetrachloride (CCl 4 ) intoxicated male Wistar rats was assessed. EAF significantly inhibited CCl 4 -induced elevation of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TB), total cholesterol (TC), and triglycerides (TG), in the blood serum and prevented lipid peroxidation and restored superoxide dismutase (SOD) activity and glutathione (GSH) content in liver tissues. The observed hepatoprotective effects of EAF, which were supported by histopathological observations as pretreatment with EAF, effectively attenuated the CCl 4 -induced histopathological changes. In conclusion, EAF of Eugenia uniflora leaves has substantial hepatoprotective activities against CCl 4 induced acute liver injury in rats due to its antioxidant activity.

The phenolic profile of the leaves of Beta vulgaris subspecies vulgaris variety rubra was investigated by high-performance liquid chromatography (HPLC) coupled to electrospray ionization high resolution mass spectrometric (ESI-HRMS-MS) detection. Mass spectrometry-based molecular networking was employed to dereplicate the known compounds. Twelve known compounds, seven of which are previously undescribed as constituents in the B. vulgaris leaves were dereplicated and assigned with various levels of identification confidence. The ameliorative effects of the aqueous methanolic extract of the leaves were assessed against alloxan induced diabetic rats. It was found that the extract significantly decreased (p < 0.001) serum glucose, lipid profile, ALT, AST, TNF-α, IL-1β, IL-6, and hepatic MDA levels; and significantly increased (p < 0.001) hepatic TAO and GSH; and down-regulated the expression of hepatic NF-κB versus the untreated diabetic groups, in a dose-dependent manner. In molecular docking, all identified compounds exhibited good glide score against the PPAR-ɣ target, confirming the in vivo observed activities. In conclusion, B. vulgaris has immunomodulatory / antioxidant effects that could be helpful in slowing the progression of diabetic complications., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Punica granatum peel (PGP) is widely used in traditional medicinal purposes for chronic wounds owing to containing natural phenolics active components. In current study, active wound dressing hydrogel for chronic wound healing was prepared based on P. granatum peel crude extract (PGPC), ethyl acetate fraction (PGPEA) and their silver nanoforms (Ag-NPs). Methacrylated chitosan was synthesized as precursor to hydrogel and crosslinked by divinyl sulfone (DVS) in mild condition. Hydrogel was fully characterized by spectral morphological, mechanical and physical analyses. The integration of PGPEA silver nanoforms was formed with particle size of 15-56 nm to show minimum inhibitory concentration (MIC) equal 63 for Staphylococcus aureus and 125 for Pseudomonas aeruginosa. The hydrogel-based wound dressing with/without the active ingredients showed acceptable cytotoxicity against fibroblast human cells for PGPC and PGPEA fraction over the silver nanoforms. Rat as animal model was considered to show the impact of the active wound dressing on diabetic wounds which was proved by histopathological examination. In addition, the significant intensity of immunopositivity signals of the transforming growth factor beta (TGF-β1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the epidermal cells have revealed the efficiency of Ag NPs-PGPEA-chitosan hydrogel for chronic wound curing., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Reactive oxygen species (ROS) are involved in the pathophysiology of several health disorders, among others inflammation. Polyphenols may modulate ROS related disorders. In this work, thirty-two phenolic compounds were tentatively identified in a leaf extract from Eugenia supra-axillaris Spring. ex Mart. using HPLC-MS/MS, five of which were also individually isolated and identified. The extract displayed a substantial in vitro antioxidant potential and was capable of decreasing ROS production and hsp-16.2 expression under oxidative stress conditions in vivo in the Caenorhabditis elegans model. Also, the extract showed higher inhibitory selectivity towards COX-2 than COX-1 in vitro with higher selectivity towards COX-2 than that of diclofenac. The extract also exhibited anti-inflammatory properties: It attenuated the edema thickness in a dose dependent fashion in carrageenan-induced hind-paw odema in rats. In addition, the extract reduced the carrageenan-induced leukocyte migration into the peritoneal cavity at the highest dose. Furthermore, the extract showed antipyretic and analgesic activities in a mouse model. Eugenia supra-axillaris appears to be a promising candidate in treating inflammation, pain and related oxidative stress diseases.

In the current work, the phytochemical composition of a leaf methanol extract from Albizia anthelmintica was thoroughly investigated. The antioxidant, anti-inflammatory, analgesic, and antipyretic activities of the extract were investigated. In the carrageenan induced hind paw edema bioassay; the extract significantly reduced the edema thickness in rats and diminished the leukocyte migration to the peritoneal cavity in mice. The extract exhibited central and peripheral anti-nociceptive effects; it significantly decreased the number of acetic acid induced writhes and prolonged the latency time in the hot plate test. The extract showed a substantial antipyretic activity as it decreased significantly the elevated rectal temperature in mice after intraperitoneal injection of Brewer's yeast. Molecular docking of some major compounds in the extract to COX-1, COX-2 and 5-LOX, enzymes involved in the inflammation cascade, revealed appreciable interactions with the conserved amino acid residues in these target proteins. These findings were confirmed with in vitro enzyme inhibitory assays in which the extract showed IC 50 values of 4.11, 0.054, and 1.74 μg/mL towards COX-1, COX-2 and 5-LOX, respectively. The extract displayed solid antioxidant properties as well with a TAC value of 35.13 U/L and EC 50 of 5.36 μg/mL in DPPH assay. These findings suggested that Albizia anthelmintica is a good antioxidant with potential therapeutic efficacy for treating inflammation, pain and related oxidative stress disorders., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The wax apple ( Syzygium samarangense ) is traditionally employed as an antibacterial and immunostimulant drug in traditional medicine. This plant is rich in different flavonoids and tannins. In this study, we isolated two compounds from S. samarangense leaves: myricitrin and 3,5-di- O -methyl gossypetin. Then, we investigated the mechanisms of action of the two compounds against oxidative stress (induced by sodium arsenite) and inflammation (induced by UV light) on human keratinocytes. We could clearly demonstrate that the pre-treatment of cells with both compounds was able to mitigate the negative effects induced by oxidative stress, as no alteration in reactive oxygen species (ROS) production, glutathione (GSH) level, or protein oxidation was observed. Additionally, both compounds were able to modulate mitogen-activated protein kinase (MAPK) signaling pathways to counteract oxidative stress activation. Finally, we showed that 3,5-di- O -methyl gossypetin exerted its antioxidant activity through the nuclear transcription factor-2 (Nrf-2) pathway, stimulating the expression of antioxidant proteins, such as HO-1 and Mn-SOD-3., Competing Interests: The authors declare no conflict of interest.

A hitherto unknown polyoxygenated flavonol robinobioside (gossypetin-3- O - β -d-robinobioside) was isolated from the leaves of Caesalpinia gilliesii along with thirteen known phenolic secondary metabolites. The isolated compounds were characterized using spectroscopic analysis, including 1D and 2D NMR and mass spectrometry (MS) analyses. The extract reduced the level of liver damage in CCl₄-induced liver injury in rats. A decrease of the liver biomarkers-aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and an increase of total antioxidant capacity (TAC) levels-were observed similar to the liver protecting drug silymarin. In addition, the extract showed promising activity against carrageenan-induced paw edema in rats and protected their stomachs against ethanol-induced gastric ulcers in a concentration dependent fashion. The observed activities could be attributed to the high content of antioxidant polyphenols. Our results suggest that the C. gilliesii has the capacity to scavenge free radicals and can protect against oxidative stress, and liver and stomach injury.

Albizia harveyi is a tropical deciduous tree, found across South and Eastern Africa and widely used in traditional medicine. The leaf extract ameliorated the damaging effects of the frozen-thawing process in cryopreserved bull semen. In a dose-dependent pattern, sperm motility, viability, and membrane integrity were improved compared to the untreated control. Furthermore, the extract increased the percentage of viable sperm cells and reduced the percentages of early apoptotic and apoptotic sperm cells as well as the damage in sperm ultra-structure. These activities are in agreement with the robust antioxidant properties in vitro and in the seminal fluid as observed in the total antioxidant capacity and the lipid peroxidation parameter malondialdehyde. LC-MS yielded 35 compounds. The extract was dominated by quercetin- O -galloyl-hexoside and quercetin- O -pentoside, along with other flavonoid glycosides. The polyphenols are probably responsible for the observed activities. In conclusion, the current findings show that A. harveyi leaves are rich in bioactive polyphenols with functional properties, validating its traditional use., Competing Interests: The authors declare no conflict of interest.

Background: Caesalpinia gilliesii Hook is an ornamental shrub with showy yellow flowers. It was used in folk medicine due to its contents of different classes of secondary metabolites. In our previous study, dichloromethane extract of C. gilliesii flowers showed a good antioxidant activity., Aim of the Study: Isolation and identification of bioactive hepatoprotective compounds from C. gilliesii flowers dichloromethane fraction., Materials and Methods: The hepatoprotective activity of dichloromethane fraction and isolated compounds were studied in CCl4-intoxicated rat liver slices by measuring liver injury markers (alanine aminotransferase, aspartate aminotransferase and glutathione [GSH]). All compounds were structurally elucidated on the basis of electron ionization-mass spectrometry, one- and two-dimensional nuclear magnetic resonance., Results: A new 12,13,16-trihydroxy-14(Z)-octadecenoic acid was identified in addition to the known β-sitosterol-3-O-butyl, daucosterol, isorhamnetin, isorhamnetin-3-O-rhamnoside, luteolin-7,4'-dimethyl ether, genistein-5-methyl ether, luteolin-7-O-rhamnoside, isovanillic acid, and p-methoxybenzoic acid. Dichloromethane fraction and isorhamnetin were able to significantly protect the liver against intoxication. Moreover, the dichloromethane fraction and the isolated phytosterols induced GSH above the normal level., Conclusion: The hepatoprotective activity of C. gilliesii may be attributed to its high content of phytosterols and phenolic compounds., Summary: Bioactive Hepatoprotective phytosterols and phenolics from chloroform extract of Caesalpinia gilliesii Abbreviations used: ALT: Alanine Aminotransferase; AST: Aspartate aminotransferase; GSH: Glutathione; SC50: Scavenging Capacity 50 (SC 50); COSY: Correlation spectroscopy; NMR: Nuclear Magnetic Resonance; CC: Column chromatography; EI-MS: Electron-impact mass spectrometry; HSQC: Heteronuclear single-quantum correlation.

Background: Salsola imbricata Forssk. is a shrub widely growing in Egypt, used as a camel food, traditionally, used as anti-inflammatory agent. Literature survey showed no report about the anti-inflammatory activity of S. imbricata., Aim of the Study: This work was designed to study the phenolic constituents and to provide evidence for the traditional use of S. imbricata as an anti-inflammatory agent., Materials and Methods: The in vitro anti-inflammatory activity of the total aqueous methanol extract and some isolated compounds were investigated in RAW 264.7 macrophage cells using nitric oxide assay. All chemical structures were identified on the basis of electrospray ionization-mass spectrometry, one- and two-dimension nuclear magnetic resonance., Results: Nine phenolic compounds, among them two new natural products; isorhamnetin-3-O-β-D-glucuronyl (1'''→4'') glucuronide (1) and its dimethyl ester; isorhamnetin-3-O-β-D-di glucuronate dimethyl ester (2), two isorhamnetin glycosides: Isorhamnetin-3-O-β-D-galactopyranoside (3), isorhamnetin-3-O-β-D-glucopyranoside (4), and isorhamnetin (5). In addition, an alkaloidal phenolic; trans N-feruloyl tyramine (6), three phenolic acids: Isovanillic acid (7), ferulic acid (8), and p-hydroxy benzoic acid (9) were isolated from salsola imbricata leaves. All compounds were isolated and identified for the first time from this plant except compound (6). The extract and the tested compounds showed distintict anti-inflammatory activities with no toxicity on RAW 264.7 macrophage cells., Conclusion: The extract and the tested compounds showed distintict anti-inflammatory activities with no toxicity on RAW 264.7 macrophage cells., Summary: Investigation of the chemical constituents of the leaves of Salsola imbricata led to isolation of two new isorhamnetin derivatives: isorhamnetin.3-O-β-D.glucuronyl (1'"→") glucuronide (1) and its dimethyl ester (2), together with seven known phenolic compounds. The extract and the tested compounds showed distintict anti-inflammatory activities with no toxicity on RAW 264.7 macrophage cells. Abbreviations used: PC: Paper chromatography, MPLC : Medium Pressure Liquid Chromatography, HMBC: Heteronuclear multiple bond correlation, HMQC: Heteronuclear single quantum correlation, NMR: Nuclear magnetic resonance.

Chemical and biological investigations of the extract of Ammania auriculata (Lytheraceae) resulted in the identification of eight polyphenols (1 - 8) for the first time from this plant, including the gallotannin, 2,3,6-tri-O-galloyl-(α,β)-4C1-glucopyranose (8), for which 1D and 2D-NMR spectra were recorded and assigned for the first time. The structures of all isolates (1 - 8) were elucidated by conventional methods, spectroscopic analysis, including 1D and 2D NMR, and by HR-ESIMS as well. All of the isolated compounds were evaluated for their antioxidant activities, determined by the DPPH and ORAC methods and for their cytotoxicity against the keratinocyte cell line HaCaT using the neutral red assay (NRU) and cell cycle analysis. Compounds 1, 3, 4, 5, and 6 significantly inhibited reactive oxygen species production with ED50 values between 3.22 and 9.79 μg/ml. Compounds 1, 3, 4, and 5 showed cytotoxic activity against HaCaT cells with IC50 values between 30.7 and 84.1 μg/ml. The new galloyl glucose (8) was found not cytotoxic. Ellagitannins, 2,3-hexahydroxy-((α/β)-glucopyranose (1) and 1 -0-galloyl 2,3-hexahydroxy-(α)-glucopyranose (5) possess remarkable antioxidative and comparably weak cytotoxic activity.