Ethylene production and antioxidant potential of five peach cultivars during maturation.

Numerous biochemical processes are involved in fruit maturation, such as ethylene production, phenolic compounds accumulation, and antioxidant enzymes production. Therefore, the aim of the present work was the evaluation of ethylene production, and the bioactive compounds change in the exocarp and mesocarp of five peach [Prunus persica (L.)] cultivars during three ripening stages, (1) early ripening (ER), (2) commercial maturation, and (3) full ripening (FR) in order to establish the best stage to harvest each peach variety. The experiment was applied to five peach cultivars growing within an arid bioclimatic environment covering the whole peach production season: two early cultivars, Flordastar and Early Maycrest; one variety of mid-season Rubirich; and two late cultivars, Sweet Cap and O'Henry. Ethylene production, phenolic compounds, and oxidative stress through antioxidant enzyme activities (catalase, peroxidases [PODs] Class III, and ascorbate-POD), malondialdehyde (MDA), and hydrogen peroxide (H2 O2 ) production were determined in the exocarp and mesocarp of peach fruits. The results showed a significant increase in ethylene production during fruit ripening. However, a parallel decrease in the level of phenolic compounds as well as in antioxidant enzyme activities was observed. The FR stage was also characterized by an important accumulation of MDA and H2 O2 . In conclusion, important changes in fruit quality associated with the production level of ethylene were observed. Fruits harvested during the ER stage would be more suitable for delivering to distant markets and more appreciated by the peach industries due to their highest phenolic acid content, best antioxidant enzyme activities, and lowest oxidative stress indicator.

Metabolomics Profiling of Tunisian Sonchus oleraceus L. Extracts and Their Antioxidant Activities.

Sonchus oleraceus (L.) L. (Asteraceae) is an edible wild plant, known for its uses in traditional medicine. The aim of this study is to explore the phytochemical composition of the aerial parts (AP) and roots (R) of aqueous extracts of Sonchus oleraceus L. growing in Tunisia, using liquid chromatography-tandem mass spectrometry(LC/MS/MS), and determine the content of polyphenols and antioxidant activities. Results showed that aqueous extracts of AP and R contained, respectively, 195.25±33 µg/g and 118.66±14 µg/g gallic acid equivalent (GAE), and 52.58±7 µg/g and 3.2±0.3µg/g quercetin equivalent. AP and R extracts also contained tannins, 581.78±33 µg/g and 948.44±19 µg/g GAE. The AP extract in the 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activities, hydroxyl radical scavenging (OH-) and in cupric reducing antioxidant activity (CUPRAC) assays were respectively 0.325±0.036 mg/mL, 0.053±0.018 mg/mL, 0.696±0.031 mg/mL and 60.94±0.004 µMTE/g, while the R extract using the same assays showed, 0.209±0.052 mg/mL, 0.034±0.002 mg/mL, 0.444±0.014 mg/mL and 50.63±0.006 µM Trolox equivalent/g, respectively. A total of 68 compounds were tentatively identified by LC/MS/MS in both extracts in which quinic acid, pyrogallol, osthrutin, piperine, gentisic acid, fisetin, luteolin, caffeic acid, gingerol, were the most abundant in the LC/MS/MS spectrum. Many of these metabolites were found for the first time in Tunisian Sonchus oleraceus L. which may take account for the antioxidant activities exhibited by the plant.

Integrating virtual screening, pharmacoinformatics profiling, and molecular dynamics: identification of promising inhibitors targeting 3CLpro of SARS-CoV-2.

Introduction: The pursuit of effective therapeutic solutions for SARS-CoV-2 infections and COVID-19 necessitates the repurposing of existing compounds. This study focuses on the detailed examination of the central protease, 3-chymotrypsin-like protease (3CLpro), a pivotal player in virus replication. The combined approach of molecular dynamics simulations and virtual screening is employed to identify potential inhibitors targeting 3CLpro. Methods: A comprehensive virtual screening of 7120 compounds sourced from diverse databases was conducted. Four promising inhibitors, namely EN1036, F6548-4084, F6548-1613, and PUBT44123754, were identified. These compounds exhibited notable attributes, including high binding affinity (ranging from -5.003 to -5.772 Kcal/mol) and superior Induced Fit Docking scores (ranging from -671.66 to -675.26 Kcal/mol) compared to co-crystallized ligands. Results: In-depth analysis revealed that F6548-1613 stood out, demonstrating stable hydrogen bonds with amino acids His41 and Thr62. Notably, F6548-1613 recorded a binding energy of -65.72 kcal/mol in Molecular Mechanics Generalized Born Surface Area (MMGBSA) simulations. These findings were supported by Molecular Dynamics simulations, highlighting the compound's efficacy in inhibiting 3CLpro. Discussion: The identified compounds, in compliance with Lipinski's rule of five and exhibiting functional molecular interactions with 3CLpro, present promising therapeutic prospects. The integration of in silico methodologies significantly expedites drug discovery, laying the foundation for subsequent experimental validation and optimization. This approach holds the potential to develop effective therapeutics for SARS-CoV-2.

Design of 3D Hybrid Plant Extract/Marine and Bovine Collagen Matrixes as Potential Dermal Scaffolds for Skin Wound Healing.

Tissue engineering involves the use of smart biomimetic hybrid matrices to reinforce the cellular interaction with the matrix and restore native properties after regeneration. In this study, we highlight the potential of 3D collagen sponges soaked with bioactive extract, to enhance the wound healing process in vivo. Acid-soluble collagen from two sources, marine and bovine, were extracted and characterized physiochemically using Fourier transform infrared spectroscopy (FTIR) and SDS-PAGE. Our results confirmed that the extracted collagens were mainly composed of collagen type I with slight molecular structure differences. Both collagens present two different α chains (α1 and α2) and one ß chain. Highly interconnected 3D scaffolds from collagen from the skin are designed and added by the widely known healing plants Pistacia lentiscus and Calendula officinalis. The resulting 3D collagen matrices possess fine biocompatibility with skin cells, Hacat (keratinocytes), and 3T3-L1 (fibroblasts) cells. To evaluate the potential wound healing effect, a collagen sponge soaked with the bioactive extract was tested on BALB/c mice. Our findings confirmed that sponges significantly improve animal re-epithelialization by increasing wound closure. Consequently, spongy collagen scaffolds loaded with Pistacia lentiscus and Calendula officinalis could be used as potential wound dressing material.

Evaluation of Two Water Deficit Models on Phenolic Profiles and Antioxidant Activities of Different Peach Fruits Parts.

The present work was designed to evaluate the effects of two water shortage strategies on the phenolic profile and antioxidants activities of four Prunus persica L. cultivars (Flordastar, Early May crest, Rubirich and O'Henry). Over the course of two successive seasons (2016 and 2017), three different irrigation strategies were tested: full irrigation (FI: 100 % crop evapotranspiration (Etc)), sustained deficit irrigation (SDI: 50 % ETc), and cyclic deficit irrigation (CDI: irrigation at 100 % field capacity with a soil moisture of 50 % field capacity). HPLC-UV/VIS profile of phenolic compounds, enzymatic and non-enzymatic antioxidant activities were assessed in exocarp and mesocarp. The results showed that deficit irrigation improved the content of phenolic compounds and the antioxidant activities. In O'Henry, ascorbate peroxidase activity increased significantly under CDI in exocarp (249 %). In conclusion, most cultivars showed an improvement of the fruit quality under SDI, whereas O'Henry fruits gathered the highest phenolic amounts and displayed the best antioxidant activity under CDI.

Assessment of hypolipidemic, anti-inflammatory and antioxidant properties of medicinal plant Erica multiflora in triton WR-1339-induced hyperlipidemia and liver function repair in rats: A comparison with fenofibrate.

Hyperlipidemia is a serious health threat that has been linked to oxidative stress and systemic inflammation, causing among many other disorders essentially liver disease. The current study was conducted to evaluate the antihyperlipidemic, antioxidant and anti-inflammatory potential of methanol leaf extract from Erica multiflora (M-EML). Triton WR-1339-induced hyperlipidemic rats were divided into six groups: control group (CG), hyperlipidemic group (300 mg/kg body weight "BW") (HG), hyperlipidemic group treated with M-EML (150 and 250 mg/kg) (HG + M-EML), normal rats treated with M-EML (250 mg/kg) and fenofibrate-treated group (HG + FF) (65 mg/kg). After 24 h of administration, triton WR-1339 induced a significant increase in lipid profile, atherogenic index (AI) and Coronary Risk Index (CRI) in HG group compared to control group. Furthermore, triton WR-1339 administration induced alteration in the status of pro-inflammatory markers (aspartate transaminase, alanine transaminase, IFN-γ and Nitric oxide production). HG group showed also, a high level of lipid peroxidation, an altered antioxidant enzyme profiles and an increase in DNA damages, in liver. However, orally administration of M-EML mitigates significantly these disorders, proving hence a protective potential against triton WR-1339-induced hyperlipidemia. These findings suggest that M-EML extract could be used as functional foods and natural adjuvant treatment of hyperlipidemia.

Heat treatment improves the immunomodulatory and cellular antioxidant behavior of a natural flavanone: Eriodictyol.

Plants and natural molecules are generally consumed not in raw state but after different processing conditions (heating, mechanical agitation or cooking). The understanding of the chemistry and biological outcome of thermal treatment is still scarce. In the current study, Eriodictyol, a natural flavanone, has undergone heat treatment, generating hence three different products ((3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid, (3-(3,4-dihydroxyphenyl) propanal) and an unidentified component). The consequences of aforementioned treatment on the immunomodulatory behavior of resulted molecules were evaluated. The amount of nitric oxide production and the lysosomal enzyme activity were determined in vitro on mouse peritoneal macrophages. The kinetic of cellular antioxidant activity in splenocytes and macrophages was measured. The present investigation demonstrates that heat-processed eriodictyol significantly enhanced the proliferation of lymphocytes B and T compared to native eriodictyol. Indeed, this compound showed an important improvement on cytotoxic T lymphocyte (CTL) and natural killer (NK) activities. In addition, the production of nitric oxide (NO) and suppression of phagocytic activity of activated macrophages have been increasingly important after thermal processing. Furthermore, it was also revealed that heat-treated Erio in comparison with the native (non heat-treated) molecule has a highest cellular anti-oxidant activity in splenocytes and macrophages cells. These findings highlight the importance of heat-process as feasible and effective strategy to improve the immunomodulatory and the antioxidant efficiency of an known flavanone Eriodictyol.

Immunomodulatory and cellular anti-oxidant activities of caffeic, ferulic, and p-coumaric phenolic acids: a structure-activity relationship study.

Many studies have been performed to assess the potential utility of natural products as immunomodulatory agents to enhance host responses and to reduce damage to the human body. To determine whether phenolic compounds (caffeic, ferulic, and p-coumaric acids) have immunomodulatory effects and clarify which types of immune effector cells are stimulated in vitro, we evaluated their effect on splenocyte proliferation and lysosomal enzyme activity. We also investigated the activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL). In addition, induction of the cellular antioxidant activity in splenocytes, macrophages, and red blood cells was determined by measuring the fluorescence of the DCF product. The study first results indicated that caffeic, ferulic, and p-coumaric acids significantly promote LPS-stimulated splenocyte proliferation, suggesting a potential activation of B cells, and enhanced humoral immune response in hosts treated by the tested natural products. Phenolic acids significantly enhanced the killing activity of isolated NK and CTL cells but had negligible effects on mitogen-induced proliferation of splenic T cells. We showed that caffeic acid enhances lysosomal enzyme activity in murine peritoneal macrophages, suggesting a potential role in activating such cells. Immunomodulatory activity was concomitant with the cellular antioxidant effect in macrophages and splenocytes of caffeic and ferulic acids. We conclude from this study that caffeic, ferulic, and p-coumaric acids exhibited an immunomodulatory effect which could be ascribed, in part, to their cytoprotective effect via their antioxidant capacity. Furthermore, these results suggest that these natural products could be potentially used to modulate immune cell functions in physiological and pathological conditions.

In vitro and in vivo anti-melanoma effects of Daphne gnidium aqueous extract via activation of the immune system.

The purpose of this study was to assess the antitumor and immunomodulatory effects of the aqueous extract from Daphne gnidium in mice-bearing melanoma tumor. Balb/C mice were subcutaneously implanted with B16-F10 cells and treated intraperitoneally with the aqueous extract at 200 mg/Kg b.w for 21 days. After euthanization on day 22, the tumors were weighed; lymphocyte proliferation, cytotoxic T lymphocyte (CTL), and natural killer (NK) cell activities were evaluated using the MTT assay. Macrophage phagocytosis was studied by measuring the lysosomal activity. In addition to its potential to inhibit the growth of the transplantable tumor, the aqueous extract remarkably induced splenocyte proliferation and both NK and CTL activities in tumor-bearing mice. The aqueous extract was also seen to have promoted lysosomal activity of host macrophages.

Flavones induce immunomodulatory and anti-inflammatory effects by activating cellular anti-oxidant activity: a structure-activity relationship study.

Flavonoids impart a variety of biological activities, including anti-oxidant, anti-inflammatory, and anti-genotoxic effects. This study investigated the effects of flavone luteolin and apigenin on immune cell functions, including proliferation, natural killer (NK) cell activity, and cytotoxic T lymphocyte (CTL) activity of isolated murine splenocytes. We report for the first time that flavones enhance lymphocyte proliferation at 10 µM. Luteolin and apigenin significantly promote lipopolysaccharide (LPS)-stimulated splenocyte proliferation and enhance humoral immune responses. Luteolin induces a weak cell proliferation of lectin-stimulated splenic T cells, when compared to apigenin. In addition, both flavones significantly enhance NK cell and CTL activities. Furthermore, our study demonstrated that both flavones could inhibit lysosomal enzyme activity, suggesting a potential anti-inflammatory effect. The anti-inflammatory activity was concomitant with the cellular anti-oxidant effect detected in macrophages, red blood cells, and splenocytes. We conclude from this study that flavones exhibited an immunomodulatory effect which could be ascribed, in part, to its cytoprotective capacity via its anti-oxidant activity.

The effects of caffeic, coumaric and ferulic acids on proliferation, superoxide production, adhesion and migration of human tumor cells in vitro.

Reactive oxygen species are well-known mediators of various biological responses. In this study, we examined the effect of three phenolic acids, caffeic, coumaric and ferulic acids, on superoxide anion production, adhesion and migration of human lung (A549) and colon adenocarcinoma (HT29-D4) cancer cell lines. Proliferation of both tumor cells was inhibited by phenolic acids. Caffeic, coumaric and ferulic acids also significantly inhibited superoxide production in A549 and HT29-D4 cells. Superoxide anion production decreased by 92% and 77% at the highest tested concentration (200 µM) of caffeic acid in A549 and HT29-D4 cell lines respectively. Furthermore, A549 and HT29-D4 cell adhesion was reduced by 77.9% and 79.8% respectively at the higher tested concentration of ferulic acid (200 µM). Migration assay performed towards A549 cell line, revealed that tested compounds reduced significantly cell migration. At the highest concentration tested (200 µM), the covered surface was 7.7%, 9.5% and 35% for caffeic, coumaric or ferulic acids, respectively. These results demonstrate that caffeic, coumaric and ferulic acids may participate as active ingredients in anticancer agents against lung and colon cancer development, at adhesion and migration steps of tumor progression.

Evaluation of the antimutagenic, antigenotoxic, and antioxidant activities of Eriobotrya japonica leaves.

CONTEXT: The leaves of Eriobotrya japonica (Thunb.) Lindl. (Rosaceae) are used in traditional medicine to treat inflammatory diseases. However, information about the antigenotoxic and antioxidant properties of its leaves remains to be elucidated. OBJECTIVE: The objective of this work was to evaluate the mutagenic/antimutagenic, genotoxic/antigenotoxic, and antioxidant potentials of aqueous and total oligomers flavonoid (TOF) extracts from E. japonica. MATERIALS AND METHODS: The mutagenic/antimutagenic and genotoxic/antigenotoxic potentials of extracts (50, 250, and 500 µg/plate) were evaluated, respectively, by the Ames test with 48 h incubation and the SOS chromotest test with 2 h incubation. The antioxidant capacity of these extracts (ranging from 50 to 700 µg/mL) was tested using xanthine/xanthine oxidase and the deoxyribose assays. RESULTS: Eriobotrya japonica extracts showed neither mutagenic nor genotoxic effect. The highest protective effect against methyl methanesulfonate and 2-aminoanthracene was obtained in the presence of aqueous extract, with IC50 values of 80 and 140 µg/plate, respectively, against S. typhimurium TA104. Moreover, this extract (500 µg/plate) was also able to reduce significantly the genotoxicity induced by nitrofurantoin and aflatoxin B1 with IC50 values of 140 and 240 µg/assay, respectively. Likewise, aqueous and TOF extracts inhibited xanthine oxidase and superoxide anion formation with IC50 values ranging from 45 to 95 and from 70 to 90 µg/mL, respectively. However, TOF extract is more efficient in inhibiting hydroxyl radical and chelating iron ion with IC50 values of 140 and 400 µg/mL, respectively, when compared with the aqueous extract. CONCLUSION: Eriobotrya japonica prevents the genotoxicity of some carcinogenic substances probably thanks to its antioxidant capacities.

Flavones inhibit the proliferation of human tumor cancer cell lines by inducing apoptosis.

Dietary flavonoids have been shown to exert specific cytotoxicity toward some cancer cells, but the precise molecular mechanisms are still not completely understood. In this study, cytotoxic effects of flavones (apigenin and luteolin) on two different cancer cell lines, including human chronic myelogenous erythroleukaemia (K562) and bladder carcinoma (RT112), were determined, and the molecular mechanisms responsible for their cytotoxic effects were studied. The results of an MTT assay showed that luteolin and apigenin were able to induce cytotoxicity in K562 and RT112 cells in a dose- and time-dependent manner. The cytotoxic potency of luteolin was higher than that of apigenin. Flow-cytometry and DNA-fragmentation analysis indicated that the cytotoxicity induced by luteolin and apigenin was mainly due to apoptosis, with minor cell-cycle perturbations. This apoptotic response was characterized by an increase of the sub-G1 fraction of treated cells, poly(ADP-ribose) polymerase proteolysis, typical ladder of DNA fragmentation, and Annexin V-positive cells. In conclusion, luteolin and apigenin exert cytotoxic effects in different cancer cell lines in which apoptosis plays an important role. Thus, flavones could be considered as potential chemotherapeutic agents.

Relationship correlation of antioxidant and antiproliferative capacity of Cyperus rotundus products towards K562 erythroleukemia cells.

A Total Oligomers Flavonoids (TOFs) and ethyl acetate extracts of Cyperus rotundus were analyzed, in vitro, for their antioxidant activity using several biochemical assays: the xanthine (X)/xanthine oxidase (XO), the lipid peroxidation induced by H(2)O(2) in K562 human chronic myelogenous leukemia cells and the DNA damage in pKS plasmid DNA assay induced by H(2)O(2)/UV-photolysis and for their apoptotic effect. TOF and ethyl acetate extracts were found to be efficient in inhibiting xanthine oxidase with IC(50) values of 240 and 185 microg/ml and superoxide anion with IC(50) values of 150 and 215 microg/ml, respectively. Also, all the extracts tested were effective in reducing the production of thiobarbituric acid reactive substances (TBARS) and were able to protect against H(2)O(2)/UV-photolysis induced DNA damage. The highest activity, measured as equivalents of MDA concentration, was observed in the ethyl acetate extract (MDA=2.04 nM). In addition, the data suggest that only TOF enriched extract exerts growth inhibition on K562 cells through apoptosis induction. Therefore, these extracts were subjected to further separation by chromatographic methods. Thus, three major compounds (catechin, afzelechin and galloyl quinic acid) were isolated from the TOF enriched extract and five major compounds (luteolin, ferulic acid, quercetin, 3-hydroxy, 4-methoxy-benzoic acid and 6,7-dimethoxycoumarin) from ethyl acetate extract. Their structures were determined by spectroscopic data analysis and comparison with the literature. In addition, we evaluate the biological activities of the catechin, ferulic acid and luteolin. This investigation has revealed that the luteolin was the most active in reducing the production of TBARS (MDA=1.5 nM), inhibiting significantly the proliferation of K562 cells (IC(50)=25 microg/ml) and protecting against H(2)O(2)/UV-photolysis induced DNA damage. In conclusion, the study reveals that the ability of C. rotundus to inhibit the enzyme xanthine oxidase (XO), the lipid peroxidation and to exert apoptotic effect, may explain possible mechanisms by which C. rotundus exhibits its health benefits.