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The essential oil extracted from the leaves and flowers of Phlomis crinita Cav. ssp. mauritanica Munby were obtained by steam distillation and analyzed by gas chromatography coupled with mass spectrometry. The major constituents of flower oil were β-caryophyllene (58.1%) and germacrene D (35.1%). This oil inhibited the growth of Staphylococcus aureus, Enterococcus faecalis, and Salmonella typhimurium with minimal inhibition concentrations (MIC) varying between 39 and 625 µg/ml. The essential oil obtained from the leaves was mainly composed of trans-caryophyllene (40.8%) and germacrene D (39.1%) and exhibited an antimicrobial profile against the same strains mentioned above with MIC between 156 µg/ml and 2.5 mg/ml. [ABSTRACT FROM AUTHOR]

A new polyphenolic natural substance: 2,5-dihydroxy-benzoic acid 3'-formyl-5'-hydroxy-phenyl ester (1), Anamighrinal and 3-(O-α-L-rhamnosyl) quercetin (2) have been isolated from the methanolic aerial part extract of the plant Anagallis monelli by chromatographic separation. Their structures have been deduced essentially by one and two NMR spectroscopic procedures and mass spectrometry. Antioxidant, mutagenic, antimutagenic activities, of the natural products were realised and positive results were recorded. [ABSTRACT FROM AUTHOR]

A pronounced antiproliferative effect on human leukemia K562 cells was shown with flavonoid-enriched extracts from Rhamnus alaternus roots and leaves, with, respectively, IC50 values of 165 and 210.73 μg/mL. High DPPH radical-scavenging activity (7.21 and 18.84 μg/mL, respectively) and antioxidative effects using the xanthine oxidase assay (IC50 values of 83.33 and 103.96 μg/mL, respectively) were detected in the presence of the two tested extracts. Although no mutagenic effect was observed when using the Salmonella typhimurium assay system with TA1535 and TA100 strains, the two tested extracts exhibited a high-level protection toward the direct mutagen, sodium azide-induced response. [ABSTRACT FROM AUTHOR]

Mutagenic and antimutagenic activities against direct acting mutagens, nifuroxazide (NF) and sodium azide (SA), and indirect acting mutagen aflatoxin B1 (AFB1) of extracts prepared from aerial parts of Pituranthos tortuosus were investigated in bacterial assay systems (i.e., the Ames test with Salmonella typhimurium TA100, TA98, TA1538, TA1535, and the SOS chromotest with Escherichia coli PQ 37). It was found that all extracts obtained from P. tortuosus decreased the mutagenicity induced by AFB1 (10 μg/assay), SA (1.5 μg/assay), and NF (20 μg/assay). Ethyl acetate, acetone, methanol, and total oligomer flavenoid extracts exhibited the highest inhibition level of mutagenicity induced by the indirect mutagen AFB1. In addition, antiproliferative and apoptotic properties of these extracts have also been reported using two leukemia cell lines, L1210 and K562. The results revealed that all extracts showed a significant cytotoxic effect on these cell lines, and the effect was greater in the presence of human K562 chronic myelogenous leukemia cells, whereas they do not induce apoptosis. [ABSTRACT FROM AUTHOR]

The mutagenic potential of aqueous, Total Oligomers Flavonoids (TOF), ethyl acetate, and methanol extracts as well as essential oil (EO) obtained from tubers of Cyperus rotundus L. was assessed by “Ames assay”, using Salmonella tester strains TA98 and TA100, and “SOS chromotest” using Escherichia coli PQ37 strain with and without an exogenous metabolic activation system (S9). None of the different extracts showed a mutagenic effect. Likewise, the antimutagenicity of the same extracts was tested using the “Ames test” and the “SOS chromotest”. Our results showed that C. rotundus extracts have antimutagenic effects with Salmonella typhimurium TA98 and TA100 strains towards the mutagen Aflatoxin B1 (AFB1), as well as with E. coli PQ37 strain against AFB1 and nifuroxazide mutagens. A free radical scavenging test was used in order to explore the antioxidant capacity of the extracts obtained from the tubers of C. rotundus. TOF, ethyl acetate and methanol extracts showed an important free radical scavenging activity towards the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical. These extracts showed IC50 values of respectively 5, 20 and 65 μg/ml. The beneficial effects of TOF, ethyl acetate, methanol and essential oil extracts of C. rotundus have been assessed by antioxidant and antimutagenic activities. [ABSTRACT FROM AUTHOR]

The petroleum ether, chloroformic, ethyl acetate, methanolic, Total Oligomers Flavonoids (TOF) enriched extracts, water extract as well as its fractions A1, A2, A3 obtained from aerial parts of Rhamnus alaternus, a Tunisian-Mediterranean medicinal species, were investigated for the contents of phenolic compounds, cytotoxic activity against the K562 human chronic myelogenous leukaemia cell line and L1210 leukaemia murine cells and for antibacterial activity against Gram positive and Gram negative bacterial reference strains. A pronounced cytotoxic effect on both the cell lines was shown in the TOF, ethyl acetate, methanolic, aqueous extracts and A2 fraction, with respectively IC50 values 75, 232, 298, 606 and 571 μg/ml on K562 cells and 198, 176, 767, 560 and 614 μg/ml on L1210 cell line. Significant activity against bacterial reference strains: Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Salmonella enteritidis and Salmonella typhimurium was shown with ethyl acetate, TOF extracts and A2 fraction. The antimicrobial and cytotoxic activities showed by R. alatemus depended on the chemical composition of the tested extracts. [ABSTRACT FROM AUTHOR]

Essential oil from the tubers of Cyperus rotundus, obtained by steam distillation, was analyzed by GC and GC/MS. In total, 33 compounds were identifi ed. The oil was characterized by its high content of sesquiterpenes with cyperene (30.9%) being major. The antibacterial activity of oil from tubers of Cyperus rotundus, showed more important activity against Gram-positive bacteria specially Staphylococcus aureus than Gram-negative bacteria. The antimutagenic activity was tested by the "SOS Chromotest" and the "Ames" test. C. rotundus oil acted as an antimutagen against Aflatoxin B1 in both Salmonella strains (TA100 and TA98) and Escherichia coli strain (PQ37) and against nifuroxazide in Escherichia coli strain (PQ37), where its mutagenicity is not expressed. The highest rates of AFB1 mutagenesis inhibition tested by Ames assay, ranged from about 82.56% for TA100 strain to 85.47% for TA98 strain at the same dose of 50 µg AFB1 per plate. Whereas, the mutagenic effect of respectively nifuroxazide and AFB1 (50 µg/assay) were reduced by aproximately 58.19% and 81.67% when tested by the SOS chromotest assay. [ABSTRACT FROM AUTHOR]

Aqueous and flavonoid-enriched extract as well as essential oil (EO) obtained from leaves of Pistacia lentiscus were assessed for antibacterial and antimutagenic activities. Antibacterial activity of different extracts and EO were evaluated against six bacterial strains. A marked inhibitory effect was observed against Salmonella typhimurium, whereas lower activity was observed against Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella enteritidis. EO showed significant inhibitory effects against Salmonella typhimurium, Salmonella enteritidis and Staphylococcus aureus. The antimutagenic activity of the different extracts against Aflatoxin B1 (AFB1) and sodium azide was demonstrated with the Salmonella typhymurium assay. The number of revertants per plate decreased significantly when the plant extracts were added to the assay system using Salmonella typhimurium TA100, TA98 and TA1535. [ABSTRACT FROM AUTHOR]

The composition of the hydrodistilled essential oil of leaves of Pistacia lentiscus L. (Anacardiaceae) was analysed by GC-MS. Twenty-seven compounds were identified, representing 58% of the total oil. α-Pinene (17%), γ-terpinene (9%) and terpinen-4-ol (12%) were characterized as the main constituents. The essential oil was tested for its antimicrobial and antimutagenic activity. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The mutagenic potential of aqueous, total oligomers flavonoids (TOF), ethyl acetate and methanol extracts from tubers of Cyperus rotundus L. was assessed using Ames Salmonella tester strains TA98 and TA100, and SOS chromotest strain Escherichia coli PQ37 with and without metabolic activation (S9). None of the different extracts produced a mutagenic effect. Likewise, the antimutagenicity of the same extracts was tested using the "Ames test" and the "SOS chromotest". Our results showed that C. rotundus extracts possess antimutagenic effects against S. typhimurium TA98 and TA100 strains towards the mutagen aflatoxin B1 (AFB1), similar to E. coli PQ37 strain against AFB1 and Nifuroxazide mutagens using the SOS chromotest assay. A free radical scavenging test was used in order to explore the antioxidant capacity of the extracts obtained from the tubers of C. rotundus. TOF, ethyl acetate and methanol extracts showed an important free radical scavenging activity towards the 1,1-diphenyl-2-picrylhydrazine (DPPH) free radical. These extracts showed an IC50 value of respectively 5, 20 and 65 µg mL-1. The beneficial effects of TOF, ethyl acetate and methanol extracts of C. rotundus were assessed by antioxidant and antimutagenic activities. [ABSTRACT FROM AUTHOR]

Aims In this study, we have investigated the effects of apigenin-7-glucoside, genkwanin and naringenin, on mouse melanoma B16F10 cell proliferation. Influence of these natural products on percentage cell distribution in cycle phases and melanogenesis was also studied. Main methods Cell viability was determined at various periods using the MTT assay, whereas effects of tested compounds on progression through the cell cycle were analyzed by flow cytometry. In addition, amounts of melanin and tyrosinase were measured spectrophotometrically at 475 nm. Besides, the mechanism involved on the death route induced by the tested molecules was evaluated using the bis-benzimide trihydrochloride coloration method (Hoechst 33258). Key findings Apigenin-7-glucoside, genkwanin and naringenin exhibited significant anti-proliferative activity against B16F10 melanoma cells after 24 and 48 h of incubation. Furthermore, apigenin-7-glucoside, genkwanin and naringenin provoked an increase of subG0/G1, S and G2/M phase cell proportion with a significant decrease of cell proportion in G0/G1 phases. The results evaluated using Hoechst 33,258, confirm that the percentage of B16F10 cells observed in the sub G0/G1 phase were undergoing apoptosis. Moreover, apigenin-7-glucoside and naringenin revealed an ability to enhance melanogenesis synthesis and tyrosinase activity of B16F10 melanoma cells. Whereas genkwanin induces a decrease of melanin synthesis by inhibiting tyrosinase activity. Significance Our results promote the introduction of genkwanin in cosmetic preparations, as skin whitening agent, whereas apigenin-7-glucoside and naringenin should be introduced into cosmetic products as natural tanning agents. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Highlights: [•] Anti-tumor and immunomodulatory effects of G extract were investigated. [•] Its cellular anti-oxidant activities was also determined. [•] G extract induced anti-melanoma effect by inhibiting tumor weight and size. [•] It increased splenocytes proliferation, NK and CTL activities in tumor-bearing mice. [•] It also enhanced cellular anti-oxidant activity in several cell types in mice. [Copyright &y& Elsevier]

In this study, we have investigated inhibitory capacity of ethyl acetate, total oligomer flavonoid (TOF), aqueous extracts and beta amyrin acetate, a triterpene isolated from ethyl acetate extract obtained from leaves of Daphne gnidium, on mouse melanoma (B16-F0 and B16-F10 cells) proliferation. Influence of these products on percentage cell distribution in cycle phases and melanogenesis was also studied. Cell viability was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and flow cytometry was used to analyse effects of tested compounds on progression through the cell cycle. In addition, amounts of melanin and tyrosinase were measured spectrophotometrically at 475 nm. Ethyl acetate, TOF and aqueous extracts exhibited significant anti-proliferative activity after incubation with the two types of tumour skin cells B16-F0 and B16-F10. Furthermore, cell cycle analysis revealed that cells treated with ethyl acetate and TOF extracts were arrested predominantly in G2-M phase. Ethyl acetate extract has also the ability to enhance melanogenesis and tyrosinase activity of B16-F0 melanoma cells. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Rutin and esculin have been polymerised by laccase. Five fractions with between 2127.42 and 8331.85g/mol for oligorutins, and between 688.12 and 6973g/mol for oligoesculins, were obtained. Fourier transformed infrared analysis showed that oligorutins were formed through C–C, C–O and Cs, while oligoesculins were obtained through C–C linkages. Monomers, their oligomers and their metabolites exhibited no mutagenic effect. Oligorutins and oligoesculins were more efficient in reducing the mutagenicity of methyl methanesulphonate, by, respectively, 69% and 64.8% in the presence of Salmonella typhimurium TA104, and 79.7% and 68.9% in the presence of S. typhimurium TA102, than were their monomers. The same oligomers revealed greater significant inhibitory effect of 2-aminoanthracene mutagenicity (respectively 82.4% and 79.3% in the presence of S. typhimurium TA104, and 89.2% and 82.9% in the presence of S. typhimurium TA102), than their monomers. Our results strongly suggest the enhancement of the tested monomer antimutagenicity after polymerisation. [Copyright &y& Elsevier]

Background: The digallic acid (DGA) purified from Pistacia lentiscus. L fruits was investigated for its antiproliferative and apoptotic activities on human lymphoblastoid TK6 cells. Methods: We attempt to characterize the apoptotic pathway activated by DGA. Apoptosis was detected by DNA fragmentation, PARP cleavage and by evaluating caspase activities. Results: The inhibition of lymphoblastoid cell proliferation was noted from 8.5 µg/ml of DGA. The induction of apoptosis was confirmed by DNA fragmentation and PARP cleavage. We have demonstrated that DGA induces apoptosis by activating the caspase-8 extrinsic pathway. Caspase-3 was also activated in a dose dependent manner. Conclusion: In summary, DGA exhibited an apoptosis inductor effect in TK6 cells revealing thus its potential as a cancer-preventive agent. [ABSTRACT FROM AUTHOR]

Abstract: The digallic acid obtained from the fruit Pistacia lentiscus exhibits an inhibitory activity against nitrofurantoine and B[a]P induced genotoxicity when tested by the SOS chromotest bacterial assay system in the presence of Escherichia coli PQ37 strain. The antioxidant activity of the tested compound was determined by its ability to scavenge the free radical , to inhibit the xanthine oxidase, involved in the generation of free radicals, and to inhibit the lipid peroxidation induced by H2O2 in the K562 cell line. Our results revealed that digallic acid shows an important free radical scavenging activity towards the radical (99%) and protection against lipid peroxidation (68%). [Copyright &y& Elsevier]

Abstract: The genus Phlomis L. belongs to the Lamiaceae family and encompasses 100 species native to Turkey, North Africa, Europe and Asia. It is a popular herbal tea enjoyed for its taste and aroma. Phlomis species are used to treat various conditions such as diabetes, gastric ulcer, hemorrhoids, inflammation, and wounds. This review aims to summarize recent research on the phytochemistry and pharmacological properties of the genus Phlomis, with particular emphasis on its ethnobotanical uses. The essential oil of Phomis is composed of four chemotypes dominated by monoterpenes (α-pinene, limonene and linalool), sesquiterpenes (germacrene D and β-caryophyllene), aliphalic compounds (9,12,15-octadecatrienoic acid methyl ester), fatty acids (hexadecanoic acid) and other components (trans-phytol, 9,12,15-octadecatrien-1-ol). Flavonoids, iridoids and phenylethyl alcohol constitute the main compounds isolated from Phlomis extracts. The pharmacological activities of some Phlomis species have been investigated. They are described according to antidiabetic, antinociceptive, antiulcerogenic, protection of the vascular system, anti-inflammatory, antiallergic, anticancer, antimicrobial and antioxidant properties. [Copyright &y& Elsevier]

Abstract: The total oligomers flavonoids (TOF), chloroform, petroleum ether and aqueous extracts from Acacia salicina, were investigated for the antioxidative, cytotoxic, antimutagenic and antigenotoxic activities. The viability of K562 cells were affected by all extracts after 48h exposure. Our results showed that A. salicina extracts have antigenotoxic and/or antimutagenic activities. TOF and chloroform extracts exhibit antioxidant properties, expressed by the capacity of these extracts to inhibit xanthine oxidase activity. To further explore the mechanism of action of A. salicina extracts, we characterized expression profiles of genes involved in antioxidant protection and DNA repair in the human lymphoblastic cell line K562 exposed to H2O2. Transcription of several genes related to the thioredoxin antioxidant system and to the DNA base-excision repair pathway was up-regulated after incubation with chloroform, TOF and petroleum ether extracts. Moreover genes involved in the nucleotide-excision repair pathway and genes coding for catalase and Mn-superoxide-dismutase, two important antioxidant enzymes, were induced after incubation with the chloroform extract. Taken together, these observations provide evidence that the chloroform and TOF extracts of A. salicina leaves contain bioactive compounds that are able to protect cells against the consequences of an oxidative stress. [Copyright &y& Elsevier]

Abstract: The effect of extracts obtained from Rhamnus alaternus L. leaves on genotoxicity and SOS response induced by aflatoxin B1 (10μg/assay) as well as nifuroxazide (20μg/assay) was investigated in a bacterial assay system, i.e., the SOS chromotest with Escherichia coli PQ37. The evaluation of the mutagenic and antimutagenic actions of the same extracts against the sodium azide (1.5μg/plate)-induced mutagenicity was assayed using the Salmonella typhimurium assay system. The R. alaternus tested extracts exhibited no genotoxicity either with or without the external S9 activation mixture. However, all the extracts, particularly aqueous extract (A) and its chloroformic fraction (A2) significantly decreased the genotoxicity induced by aflatoxin B1 and nifuroxazide. Moreover, the different extracts showed no mutagenicity when tested with Salmonella typhimurium strains TA1535 and TA1538 either with or without the S9 mix. Aqueous extract as well as its A2 fraction exhibited the highest level of protection towards the direct mutagen, sodium azide-induced response in TA1535 strain with mutagenicity inhibition percentages of 83.6% and 91.4%, respectively, at a dose of 250μg/plate. The results obtained by the Ames test assay confirm those of SOS chromotest. These same active extracts exhibited high xanthine oxidase (XOD) inhibiting with respective IC50 values of 208 and 137μg/ml, and superoxide anion-scavenging effects (IC50 values of 132 and 117μg/ml) when tested in the XOD enzymatic assay system. Our findings emphasize the potential of R. alaternus to prevent mutations and also its antioxidant effect. [Copyright &y& Elsevier]

Abstract: Phenylpropanoids play an important biological role in plants and are considered as potentially beneficial molecules for human health. For this purpose, they are used in pharmaceutic, cosmetic and food preparation. They are widely distributed in plants, from mosses to angiosperms but in low quantities and their extraction yield never exceeds 1% of the dry weight. Most of genes involved in the flavonoid biosynthesis pathway have been characterized and functionally expressed in recombinant microorganisms. In order to produce higher amount of flavonoids, several recombinant microorganisms have been constructed with diverse combination of flavonoid biosynthesis genes. Two expression systems, Escherichia coli and Saccharomyces cerevisiae are generally preferred for functional expressions. The use of these systems allow to synthetize up to 28mg/l of naringenin in small-scale culture. This indicates that the two host species are promising candidates in biotechnology processes for the production of significant quantities of flavonoids. The description of the different systems used for functional expression of flavonoid genes, in regard to new developments in metabolic, genetic and process engineering constitutes the aim of this review. [Copyright &y& Elsevier]

Abstract: Antioxidant activity of myricetin-3-o-galactoside and myricetin-3-o-rhamnoside, isolated from the leaves of Myrtus communis, was determined by the ability of each compound to inhibit xanthine oxidase activity, lipid peroxidation and to scavenge the free radical 1,1-diphenyl-2-picrylhydrazyl. Antimutagenic activity was assessed using the SOS chromotest and the Comet assay. The IC50 values of lipid peroxidation by myricetin-3-o-galactoside and myricetin-3-o-rhamnoside are respectively 160μg/ml and 220μg/ml. At a concentration of 100μg/ml, the two compounds showed the most potent inhibitory effect of xanthine oxidase activity by respectively, 57% and 59%. Myricetin-3-o-rhamnoside was a very potent radical scavenger with an IC50 value of 1.4μg/ml. Moreover, these two compounds induced an inhibitory activity against nifuroxazide, aflatoxine B1 and H2O2 induced mutagenicity. The protective effect exhibited by these molecules was also determined by analysis of gene expression as response to an oxidative stress using a cDNA micro-array. Myricetin-3-o-galactoside and myricetin-3-o-rhamnoside modulated the expression patterns of cellular genes involved in oxidative stress, respectively (GPX1, TXN, AOE372, SEPW1, SHC1) and (TXNRD1, TXN, SOD1 AOE372, SEPW1), in DNA damaging repair, respectively (XPC, LIG4, RPA3, PCNA, DDIT3, POLD1, XRCC5, MPG) and (TDG, PCNA, LIG4, XRCC5, DDIT3, MSH2, ERCC5, RPA3, POLD1), and in apoptosis (PARP). [Copyright &y& Elsevier]

Abstract: Three extracts were prepared from the leaves of Acacia salicina: aqueous, methanol, and ethyl acetate extracts. The antigenotoxic properties of these extracts were investigated by assessing the inhibition of mutagenicity of the indirect-acting mutagen benzo[a]pyrene using the Ames assay and the genotoxicity of the direct-acting mutagen, hydrogen peroxide, using the “Comet assay.” Aqueous, methanol, and ethyl acetate extracts at doses of 500, 50, and 500 μg per plate reduced benzo[a]pyrene mutagenicity by 95%, 82%, and 40%, respectively, in Salmonella typhimurium TA98 strain and by 91%, 66% and 63%, respectively, at the same doses with a TA97 assay system. Human lymphoblast cells K562 were pretreated with 50% inhibition concentration of each extracts and then treated by H2O2, for the Comet assay. The Comet assay results showed that ethyl acetate and methanol extracts decreased the DNA damage caused by H2O2 by, respectively, 34.8% and 31.3%. We envisaged also the study of the antioxidant effect of these extracts by the enzymatic xanthine/xanthine oxidase assay. Results indicated that methanol and ethyl acetate extracts were potent inhibitors of xanthine oxidase and superoxide anion scavengers. We conclude that these integrated approaches to antigenotoxicity and antioxidant assessment may be useful to help compare the beneficial effects associated with using A salicina as medicinal and dietary plant. [Copyright &y& Elsevier]

Abstract: The ability of three Rhamnus alaternus leaves extracts on antigenotoxic and gene expression level effects was respectively investigated in a bacterial assay system, i.e. the SOS chromotest with Escherichia coli PQ37 and in human K562 lymphoblast cell line. Total oligomers flavonoids (TOF) enriched, methanol and ethyl acetate extracts were prepared from powdered R. alaternus leaves and characterized quantitatively for the presence of polyphenolic compounds. We explored the response to oxidative stress using the transcriptional profile of genes in K562 cells stressed with H2O2 after incubation with plant extracts. For this purpose, we used a cDNA microarrays containing 82 genes related to cell defense, essentially represented by antioxidant and DNA repair genes. Analysis revealed that SOD1, AOE 372, TXN genes involved in the antioxidant defense system and XPC, LIG4, POLD2, PCNA genes implied in the DNA repair system were among the most expressed ones in the presence of the tested extracts. These results were in accordance with those obtained when we tested the antigenotoxic and antioxidant effects of the same extracts with, respectively the SOS chromotest and the xanthine/xanthine oxidase enzymatic assay system. The effect of the tested extracts on SOS response induced by both Aflatoxin B1 (AFB1: 10μg/assay) and nifuroxazide (20μg/assay) showed that the TOF extract exhibited the highest antimutagenic level towards the indirect mutagen AFB1. Whereas ethyl acetate extract showed the highest antimutagenic effect towards the direct mutagen, nifuroxazide. None of the tested extracts induced mutagenic activity. However all the tested extracts exhibited xanthine oxidase inhibiting and superoxide anions scavenging effects. R. alaternus extracts contain compounds with significant antioxidant and antigenotoxic activities. These compounds modulate gene expression as detected by using cDNA arrays. [Copyright &y& Elsevier]

Abstract: The effect of extracts obtained from Acacia salicina on genotoxicity and SOS response induced by Benzo(a)pyrene (B[a]P) as well as nifuroxazide was investigated in a bacterial assay system, i.e., the SOS chromotest with Escherichia coli PQ37. Preparations obtained from the leaves of A. salicina exhibited no genotoxicity either with or without the external S9 activation mixture. However, all extracts significantly decreased the genotoxicity induced by (B[a]P) and nifuroxazide. Ethyl acetate, methanol and TOF extracts exhibited the highest inhibition level of the SOS response induced by the direct mutagen nifuroxazide. Whereas, aqueous, ethyl acetate and methanol extracts displayed the greatest level of protection towards the indirect mutagen, (B[a]P), induced response. In addition to their antigenotoxic activity, TOF, aqueous, methanol and chloroform extracts showed an important free radical scavenging activity towards the 1,1-diphenyl 2-picrylhydrazyl (DPPH) free radical. These extracts showed IC50 value of 36, 73, 65, and 87μg/ml respectively. Taken together, our finding showed that A. salicina exhibits significant antioxidant and antigenotoxic activities. [Copyright &y& Elsevier]

Abstract: This study evaluates mutagenic and antimutagenic effects of aqueous, total oligomers flavonoïds (TOF), ethyl acetate and methanol extracts from aerial parts of Cyperus rotundus with the Salmonella typhimurium assay system. The different extracts showed no mutagenicity when tested with Salmonella typhimurium strains TA98, TA100, TA1535 and TA1538 either with or without the S9 mix. On the other hand, our results showed that all extracts have antimutagenic activity against Aflatoxin B1 (AFB1) in TA100 and TA98 assay system, and against sodium azide in TA100 and TA1535 assay system. TOF, ethyl acetate and methanol extracts exhibited the highest inhibition level of the Ames response induced by the indirect mutagen AFB1. Whereas, ethyl acetate and methanol extracts exhibited the highest level of protection towards the direct mutagen, sodium azide, induced response. In addition to antimutagenic activity, these extracts showed an important free radical scavenging activity towards the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical. TOF, ethyl acetate and methanol extracts showed IC50 value of 15, 14 and 20μg/ml, respectively. Taken together, our finding showed that C. rotundus exhibits significant antioxidant and antimutagenic activities. [Copyright &y& Elsevier]

The aim of the present research was to determine the chemical composition and the cytotoxic effects of Tetraclinis articulata trunk bark essential oil (HEE) obtained by steam distillation and five fractions obtained by normal phase silica chromatographic separation. Chemical analysis allowed the identification of 54 known compounds. Relatively high amounts of oxygenated sesquiterpenes (44.4–70.2%) were detected, mainly consisting of caryophyllene oxide (13.1–26.6%), carotol (9.2–21.2%),14-hydroxy-9-epi-(E)-caryophyllene (3.2–15.5%) and humulene epoxide II (2.6–7.2%). The cytotoxic activity against human mammary carcinoma cell lines (MDA-MB-231) and colorectal carcinoma cell lines (SW620) of the essential oil and its fractions were assessed. All the samples displayed moderate to weak activity compared to 5-fluorouracil. The colorectal carcinoma cell line was relatively more sensitive to the essential oil and its fractions compared to the breast cancer cell line, showing IC50 values from 25.7 to 96.5 μg/mL. In addition, the essential oil and its fraction E.2 revealed a cytotoxic activity against colorectal carcinoma cell line, with IC50 values lower than 30 μg/mL. This is the first report on the chemical composition and cytotoxic activity of the trunk bark essential oil of T. articulata. [ABSTRACT FROM AUTHOR]

The wide morbidity of obesity has heightened interest in providing natural and safe compounds to maintain optimal health. The present study was designed to determine the chemical constituents and the effects of methanol leaf extract from Erica multiflora (M-EML) on mitigating high-fat and high-fructose diet (HFFD)-induced metabolic syndrome (MS). LC-MS/MS characterization of M-EML allowed the identification of 14 secondary metabolites and showed that quercetin-3-O-glucoside and kaempferol-3-O-glucoside were the main compounds of our extract. In the in vivo study, the oral administration of M-EML (250 mg/kg) during the last 4 weeks of the experimentation alleviated HFFD-induced obesity, insulin resistance (IR) and cardiovascular diseases. Thus, M-EML treatment significantly normalized body and liver weight, allowed to a sharp decline in plasma levels of TC, TG and LDL-c by 32%, 35% and 66%, respectively. Moreover, hepatic enzymes, total and direct bilirubin, lipase and uric acid levels have been diminished in treated group. Histopathology of the liver confirmed the changes induced by HFFD and the hepatoprotective effect of M-EML. The supply of M-EML reduced NO production and cellular lysosomal enzyme activity by 44% and 60%, respectively compared to HFFD. Besides, M-EML showed decreased pro-inflammatory cytokines levels (259.5±47.35 pg/ml and 56.08±1.56 pg/ml) of TNF-α and IL-6, respectively. In addition, M-EML reduced liver malondialdehyde (MDA) content and enhanced superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. In contrast, these enzymatic activities have been disrupted in HFFD rats. Overall, M-EML prevented obesity through the modulation of metabolic syndrome, reducing inflammation and promoting antioxidant enzymes activities. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a malignancy with a high incidence. Currently, the drugs used in chemotherapy are often accompanied by strong side effects. Natural secondary metabolites can interfere with chemotherapeutic drugs and intensify their cytotoxic effects. This study aimed to profile the secondary metabolites from the methanol extract of Scabiosa atropurpurea and investigate their in vitro activities, alone or in combination with the chemotherapeutic agent doxorubicin. MTT assay was used to determine the cytotoxic activities. Annexin-V/PI double-staining analysis was employed to evaluate the apoptotic concentration. Multicaspase assay, quantitative reverse transcription real-time PCR (RT-qPCR), and ABC transporter activities were also performed. LC-MS analysis revealed 31 compounds including phenolic acids, flavonoids, and saponins. S. atropurpurea extract intensified doxorubicin anti-proliferative effects against resistant tumor cells and enhanced the cytotoxic effects towards Caco-2 cells after 48 h. The mRNA expression levels of Bax, caspase-3, and p21 were increased significantly whereas Bcl-2 expression level was decreased. Furthermore, the methanol extract reversed P-glycoprotein or multidrug resistance-associated protein in Caco-2 cells. In conclusion, S. atropurpurea improved chemosensitivity and modulated multidrug resistance in Caco-2 cells which makes it a good candidate for further research in order to develop a new potential cancer treatment. [ABSTRACT FROM AUTHOR]

Coxsackie B viruses (CV–B) are usually transmitted via the fecal-oral route and the virus gains the central nervous system (CNS) via the bloodstream. Nevertheless, other routes of spread of the virus to the CNS cannot be excluded, including the neuronal route. Neuronal cells, as well as non-neuronal cells (fibroblasts), were isolated from mice and inoculated with CV-B4 in the absence and presence of neutralizing serum. In the absence of neutralizing serum, virus titers recorded in neuron cultures and rates of infected neurons were non-significantly different compared to those recorded in fibroblast cultures. Higher cell mortality was noted among neurons than fibroblasts. The addition of neutralizing serum to neurons did not reduce significantly virus titers or rates of infected cells and cell viability was not significantly augmented, while virus titers and rates of infected fibroblasts were significantly reduced and their viability was significantly enhanced as well. Our results demonstrate the ineffectiveness of neutralizing serum to prevent neurons infection with CV-B4 which suggests a trans-synaptic transmission of CV-B4 between neurons. • Coxsackievirus B4 infects and replicates in primary neurons. • Coxsackievirus B4 neutralizing serum does not preserve primary neurons from viral cytopathic effect. • Coxsackievirus B4 neutralizing serum does not enhance the viability of primary neurons. • Coxsackievirus B4 is transmitted between neurons via synapses. [ABSTRACT FROM AUTHOR]

Despite major advances in the last 10 years, whether in terms of prevention or treatment, the 5 year survival rate remains relatively low for a large number of cancers. These therapeutic failures can be the consequence of several factors associated with the cellular modifications or with the host by itself, especially for some anticancer drugs such as cisplatin, which induces a nephrotoxicity. In the strategy of research for active molecules capable both of exerting a protective action against the deleterious effects of cisplatin and exerting a chemosensitizing action with regard to cancer cells, we tested the potential effects of Ephedra alata Decne extract (E.A.) rich in polyphenolic compounds towards a 4T1 breast cancer model in vitro and in vivo. We showed that E.A. extract inhibited cell viability of 4T1 breast cancer cells and induced apoptosis in a caspase-dependent manner, which involved intrinsic pathways. Very interestingly, we observed a synergic antiproliferative and pro-apoptotic action with cisplatin. These events were associated with a strong decrease of breast tumor growth in mice treated with an E.A./cisplatin combination and simultaneously with a decrease of hepato- and nephrotoxicities of cisplatin. [ABSTRACT FROM AUTHOR]

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. Image 1 • Protective potential of M-EML extract against triton WR-1339-induced hyperlipidemia. • M-EML extract mitigates lipoproteins and transaminases levels. • M-EML extract reduces inflammatory parameters: IFN-γ levels and NO production. • M-EML extract improves in vivo antioxidant system and reduced DNA damage. • M-EML extract could be used as a natural adjuvant treatment of hyperlipidemia. [ABSTRACT FROM AUTHOR]

Background and purpose: Lung cancer is the leading cause of death in both men and women, constituting a major public health problem worldwide. Non-small-cell lung cancer accounts for 85%-90% of all lung cancers. We propose a compound that successfully fights tumor growth in vivo by targeting the enzyme GARS1. Experimental approach: We present an in-depth investigation of the mechanism through which Fraisinib [meso-(p-acetamidophenyl)-calix(4)pyrrole] affects the human lung adenocarcinoma A549 cell line. In a xenografted model of non-small-cell lung cancer, Fraisinib was found to reduce tumor mass volume without affecting the vital parameters or body weight of mice. Through a computational approach, we uncovered that glycyl-tRNA synthetase is its molecular target. Differential proteomics analysis further confirmed that pathways regulated by Fraisinib are consistent with glycyl-tRNA synthetase inhibition. Key results: Fraisinib displays a strong anti-tumoral potential coupled with limited toxicity in mice. Glycyl-tRNA synthetase has been identified and validated as a protein target of this compound. By inhibiting GARS1, Fraisinib modulates different key biological processes involved in tumoral growth, aggressiveness, and invasiveness. Conclusion and implications: The overall results indicate that Fraisinib is a powerful inhibitor of non-small-cell lung cancer growth by exerting its action on the enzyme GARS1 while displaying marginal toxicity in animal models. Together with the proven ability of this compound to cross the blood-brain barrier, we can assess that Fraisinib can kill two birds with one stone: targeting the primary tumor and its metastases "in one shot." Taken together, we suggest that inhibiting GARS1 expression and/or GARS1 enzymatic activity may be innovative molecular targets for cancer treatment., Competing Interests: CR and GD are members of the Advisory Board of GIAM Pharma International S.A.R.L., Monthey (CH). The remaining 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. The authors declare that they were editorial board members of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ben Toumia, Bachetti, Chekir-Ghedira, Profumo, Ponassi, Di Domizio, Izzotti, Sciacca, Puglisi, Forte, Giuffrida, Colarossi, Milardi, Grasso, Lanza, Fiordoro, Drago, Tkachenko, Cardinali, Romano, Iervasi, Vargas, Barboro, Kohnke and Rosano.)

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., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Despite the progress made in treatments, melanoma is one of the cancers for which its incidence and mortality have increased during recent decades. In the research of new therapeutic strategies, natural polyphenols such as chrysin could be good candidates owing to their capacities to modulate the different fundamental aspects of tumorigenesis and resistance mechanisms, such as oxidative stress and neoangiogenesis. In the present study, we sought to determine whether chrysin could exert antitumoral effects via the modulation of angiogenesis by acting on oxidative stress and associated DNA damage. For the first time, we show a link between chrysin-induced antiproliferative effects, the activation of the DNA damage pathway, and its ability to limit angiogenesis. More specifically, herein, we show that chrysin induces single- and double-stranded DNA breaks via the activation of the DNA damage response pathway: ATM (ataxia-telangiectasia-mutated)/Chk2 (checkpoint kinase 2) and ATR (ataxia telangiectasia and Rad3-related)/Chk1 (checkpoint kinase 1) pathways. Strong activation of this DNA damage response was found to be partly involved in the ability of chrysin to limit angiogenesis and may partly involve a direct interaction between the polyphenol and DNA G-quadruplex structures responsible for the replication fork collapse. Moreover, these events were associated with a marked reduction in melanoma cells' capacity to secrete proangiogenic factor VEGF-A. The disruption of these key protein actors in tumor growth by chrysin was also confirmed in a syngeneic model of B16 melanoma. This last point is of importance to further consider the use of chrysin as a new therapeutic strategy in melanoma treatment.

Water pollution is one of the major challenges and is of serious concern in the world. Toxicities generated by industrial activities severely deteriorate aquatic and terrestrial ecosystems during their uncontrolled discharge and accentuate water scarcity problems. An adequate treatment of released effluents seems to be mandatory. This study investigated the effect of synthetic textile wastewater (STWW) before and after an innovative algal-bacterial treatment occurred under anoxic-aerobic conditions on growth and mineral contents of radish plants. The health risk assessment was performed after the consumption of irrigated plants by rats. Results revealed a significant reduction in heavy metals content in plants irrigated with treated STWW, and rats fed with these plants showed normal health status. Rats fed with plants irrigated with raw STWW showed a disturbance of their homeostasis. The innovative treatment using algal-bacteria under anoxic-aerobic conditions succeeds to reduce the toxicity of raw STWW and provide an alternative water resource able to tackle water shortage., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Despite the medico-surgical progress that has been made in the management of patients with colorectal cancer (CRC), the prognosis at five years remains poor. This resistance of cancer cells partly results from their phenotypic characteristics in connection with the epithelial-mesenchymal transition (EMT). In the present study, we have explored the ability of a polyphenol, tannic acid (TA), to counteract CRC cell proliferation and invasion through an action on the EMT. We highlight that TA decreases human SW480 and SW620 CRC cell and murine CT26 CRC cell viability, and TA inhibits their adhesion in the presence of important factors comprising the extracellular matrix, particularly in the presence of collagen type I and IV, and fibronectin. Moreover, these properties were associated with TA's ability to disrupt CRC cell migration and invasion, which are induced by transforming growth factor-β (TGF-β), as evidence in the video microscopy experiments showing that TA blocks the TGF-β1-induced migration of SW480 and CT26 cells. At the molecular level, TA promotes a reversal of the epithelial-mesenchymal transition by repressing the mesenchymal markers (i.e., Slug, Snail, ZEB1, and N-cadherin) and re-expressing the epithelial markers (i.e., E-cadherin and β-catenin). These effects could result from a disruption of the non-canonical signaling pathway that is induced by TGF-β1, where TA strongly decreases the phosphorylation of extracellular-signal regulated kinase ERK1/2, P38 and the AKT proteins that are well known to contribute to the EMT, the cell motility, and the acquisition of invasive properties by tumor cells. Very interestingly, a preclinical study of mice with subcutaneous murine tumor colon CT26 cells has shown that TA was able to significantly delay the growth of tumors without hepato- and nephrotoxicities.

Berberine hydrochloride (BRB) is an isoquinoline alkaloid with promising anticancer efficacies. However, application of BRB had been hampered by its poor aqueous solubility, low gastrointestinal absorption, and rapid metabolism. The present study takes advantage of small extracellular vesicles (sEVs) to increase both stability and efficacy of BRB. sEVs from immature dendritic cells were produced and loaded with BRB. Proliferation, migration and Matrigel assay were performed, cycle arrest and nitric oxide (NO) production were evaluated in human breast cancer cell line (MDA-MB-231) and human umbilical vein endothelial cells (HUVECs). sEVs loaded with BRB formed a stable and homogenous population with a drug entrapment efficiency near to 42%. BRB loaded into sEVs was more potent than free BRB for MDA-MB-231 and endothelial proliferation, migration, and capillary-like formation in HUVECs. The mechanisms involved a blockade of cell cycle in G0/G1 phase, increased S phase and decreased of G2/M in MDA-MB-231 and HUVECs, and inhibition of NO production in HUVECs. Altogether, sEV-loaded BRB displayed higher effects than free BRB on different steps leading to its antitumor activity and anti-angiogenic properties in vitro. Thus, sEV formulation may be considered as an innovative approach and promising delivery of BRB to prevent tumorigenesis and angiogenesis.

Rhamnus alaternus (Rhamnaceae) has been used as a laxative, purgative, diuretic, antihypertensive, and depurative. However, few scientific research studies on its antimelanoma activity have been reported. This study aimed to investigate the in vitro antimelanoma effect of an enriched total oligomer flavonoid (TOF) extract, from R. alaternus , and to identify its phytochemical compounds. The chemical composition of TOF extract was assessed by HPLC-electrospray ionization tandem mass spectrometry (HPLC/ESI-MS 2 ) analysis. Antimelanoma activity was determined on cultured tumor cell B16F10 by the crystal violet assay, the alkaline comet assay, acridine orange/ethidium bromide (AO/EB), annexin V-fluorescein isothiocyanate/ propidium iodide (V-FITC/PI) staining, the cell cycle distribution, and the wound healing assay. Regarding chemical composition, a mixture of quercetin diglucoside, quercetin-3-O-neohesperidoside, kaempferol-3-O-(2G-α-L-rhamnosyl)-rutinoside, rhamnetin hexoside, kaempferol-3-O-rutinoside, rhamnocitrin hexoside, pilosin hexoside, apigenin glucoside, and kaempferol-3-O-glucoside was identified as major phytochemical compounds of the extracts. TOF extract inhibits melanoma B16F10 cell proliferation in dose-dependent manner. The induction of apoptosis was confirmed by comet assay, AO/EB, and annexin V-FITC/PI test. TOF extract could also induce S phase cell cycle, inhibit, and delay the cell migration of B16F10 cells. The findings showed that TOF extract from R. alaternus could be a potentially good candidate for future use in alternative antimelanoma treatments.

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 ( α 1 and α 2) and one β 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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Aida Lahmar et al.)

Melanoma has become an important health problem and new treatment have become an imperative medical need. Therefore, the finding and identification of natural product with less toxic effects, capable of promoting melanoma cell death have become an important goal of research in oncotherapy. In this study, we want to investigate the anticancer activity of an enriched total oligomers flavonoids (TOF) extract of R. alaternus in melanoma cells. First, TOF was exhibited to be rich in flavones. We revealed that this extract reduced proliferation and increased of sub-G1 and S phase cells built-up in B16-F10 cells in a dose-related manner. Moreover, In Vivo, TOF reduced tumor volume and weight with percentages of inhibition of 92.4% and 92.9%, respectively. R. alaternus was also found to be effective in reducing the level of pro-inflammatory cytokine IL-6 during metastasis. Level of TH1 cytokine, such as IL-2, was significantly enhanced by TOF treatment. Indeed, the histological examination of the tumor revealed the absence of mitoses and the presence of numerous melanin pigmented macrophage cells in the R. alaternus extract-treated group that could be explained by the induction of macrophage activation and by the arrest of the cell cycle in the Sub-G1 and S phases.

Cancer is a class of diseases characterized by uncontrolled cell growth. One of the main aims of developing new therapies is to use natural resources to induce apoptosis. LC-ms/ms analysis of a methanolic extract of Ephedra alata (E.A.) allowed the identification of 20 secondary metabolites, including flavonoids, phenolic acids, and proanthocyanidins. Antiproliferative effect was assessed by crystal violet assay. Antimigration effect was tested by wound healing assay and apoptosis induction was determined by annexin binding assays, Hoechst staining, ROS production, and activation of apoptotic proteins. The results indicated that exposure of breast cancer cells to E.A. extract significantly reduced cell viability in a dose and time-dependent manner and inhibited the migration of 4T1 cells at a low dose. Moreover, treatment of cells with E.A. extract induced apoptosis, as it was detected by Annexin V/7 AAD, Hoechst staining, ROS production, and the activation of caspases.Abbreviation:BSAbovine serum albuminDMSOdimethyl sulfoxideEDTAethylenediaminetetraacetic acidLC-ms/msliquid chromatography-mass spectrometryNACN-acetyl-l-cysteinePARPpoly(ADP-ribose) polymerasePMSFphenylmethylsulfonyl fluorideRIPAradioimmunoprecipitation assay bufferROSreactive oxygen speciesRPMIRoswell park memorial instituteSDS-PAGEsodium dodecyl sulfate-polyacrylamide gel electrophoresis.

In recent years, there has been a growing interest in the screening of natural active ingredients from Eucalyptus essential oils because of their evident importance in practical utility and their undeniable therapeutic properties. Based on this, the aim of the present study was to investigate the chemical profile of the essential oils of the trunk bark of Eucalyptus torquata Luehm. (ETEO), and E. salmonophloia F. Muell. (ESEO), growing in Tunisia. The in vitro cytotoxic properties of the extracted EOs were also evaluated against two human cancer cell lines: breast carcinoma cell lines MDA-MB-231 and colorectal cancer cell lines SW620. The analysis by gas chromatography coupled with mass spectrometry (GC/MS) led to the identification of 32 compounds from the ETEO, with the dominant constituents being the monoterpenes trans-myrtanol (73.4 %) and myrtenol (4.7 %), and the apocarotene (E)-β-ionone (3.9 %). In the case of ESEO, 29 compounds were identified with trans-myrtanol (25.0 %), decanoic acid (22.1 %), nonanoic acid (9.8 %), γ-elemene (6.5 %), γ-maaliene (5.5 %), and α-terpineol (5.3 %) as the main components. The cytotoxicity of EOs against the two chosen cell lines was tested using Crystal Violet Staining (CVS) assay and 5-fluorouracil as a reference drug. The two EOs exhibited a significant dose-dependent inhibition against the viability of the used cell lines. Their inhibitory effects were particularly observed towards SW620 colon carcinoma cells with IC 50 values of 26.71±1.22 and 22.21±0.85 μg/mL, respectively, indicating that both oils were more cytotoxic for SW620 cells compared to MDA-MB-231 one., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

In the worldwide context of an impending emergence of multidrug-resistant bacteria, this research combined the advantages of multiple lipid nanoparticles (MLNs) and the promising therapeutic use of essential oils (EOs) as a strategy to fight the antibiotic resistance of three Pseudomonas aeruginosa strains with different cefepime (FEP) resistance profiles. MLNs were prepared by ultrasonication using glyceryl trioleate (GTO) and glyceryl tristearate (GTS) as a liquid and a solid lipid, respectively. Rosemary EO (REO) was selected as the model EO. REO/FEP-loaded MLNs were characterized by their small size (~110 nm), important encapsulation efficiency, and high physical stability over time (60 days). An assessment of the antimicrobial activity was performed using antimicrobial susceptibility testing assays against selected P. aeruginosa strains. The assays showed a considerable increase in the antibacterial property of REO-loaded MLNs compared with the effect of crude EO, especially against P. aeruginosa ATCC 9027, in which the minimum inhibitory concentration (MIC) value decreased from 80 to 0.6 mg/mL upon encapsulation. Furthermore, the incorporation of FEP in MLNs stabilized the drug without affecting its antipseudomonal activity. Thus, the ability to co-encapsulate an essential oil and a hydrophilic antibiotic into MLN has been successfully proved, opening new possibilities for the treatment of serious antimicrobial infections.

The multidrug resistance phenotype is a global phenomenon and causes chemotherapy failure in various cancers, such as in uterine sarcomas that have a high mortality rate. To overcome this phenotype, there is growing research interest in developing new treatment strategies. In this study, we highlight the potential of two essential oils from the Apiaceae family, Pituranthos chloranthus (PC) and Teucrium ramosissimum Desf. (TR), to act as chemopreventive and chemosensitizing agents against two uterine sarcoma cell lines, MES-SA and P-gp-overexpressing MES-SA/Dx5 cells. We found that PC and TR were able to inhibit the cell viability of sensitive MES-SA and resistant MES-SA/Dx5 cells by a slight modulation of the cell cycle and its regulators, but also through a significant induction of apoptosis. The molecular mechanism involved both caspase pathways associated with an overproduction of reactive oxygen species (ROS) and mitochondrial membrane depolarization. Very interestingly, the combination of doxorubicin with PC or TR induced a synergism to increase cell death in resistant MES-SA/Dx5 cells and, subsequently, had the benefit of decreasing the resistance index to doxorubicin. These synergistic effects were reinforced by a decrease in P-gp expression and its P-gp adenosine triphosphatase (ATPase) activity, which subsequently led to intracellular doxorubicin accumulation in resistant sarcoma cells.

Anticancer drugs, such as Mitomycin C (MMC), can interact with biological molecules and cause genetic damage in normal cells. In this respect, we investigated the potential of chrysin, a flavone known as a potent scavenger of free radicals generated by anticancer agents, to protect mice against MMC-induced genotoxicity. The amount of DNA damage in the liver, kidney and bone marrow cells, in Balb/C mice treated with MMC (6 mg/kg, i.p) and the frequency of chromosomal aberrations indicated the genotoxic effect of MMC. Besides, a significant increase in the activities of antioxidant enzymes (SOD, CAT, GPx, GST) and lipid peroxidation is revealed. On the other hand, we noticed a regression of the genotoxic effect when studying the same parameters in Balb/C mice treated with chrysin (40 mg/kg b. wt., i.p) 24 h prior to MMC (6 mg/kg, i.p) injection. This study concluded that the protective effect of chrysin against genotoxicity of MMC results partly from its antioxidant effect.

In the present work, chemical investigation of the aerial parts of Phlomis bovei de Noé an endemic species from Algeria, led to the isolation and identification of seven known compounds including five flavones glycosides: Chrysoeriol 7- O -(3''-( E et Z )- p -coumaroyl)-β-glucoside (1) , terniflorin (apigenin-7- O -(6''- E-p -coumaroyl)glucoside) (3) , apigenin-7- O -(6''-(5'''-methoxy-coumaryl) glucoside (4) , apigenin 7- O -(3″- p -coumaryl) glucoside (5) , hispidulin-7- O -glucuronide (6) and two cinnamic acid derivatives: p -coumaric acid methyl ester ( E et Z ) (2) , chlorogenic acid (7) . Compound 4 is described for the first time in the species bovei de Noé, the genus Phlomis and the Lamiaceae family. Structures elucidation was performed by comprehensive 1D and 2D NMR analyses, mass spectrometry and by comparison with literature data. Some pure compounds and extracts have been evaluated for their antioxidant activities through different methods: DPPH and ABTS assays as well as CUPRAC assay. Genotoxic and antigenotoxic activities of pure compounds were also evaluated in-vitro on Escherichia coli PQ37 cells by the SOS Chromotest.

Cisplatin (CP) is a powerful anticancer agent used in the treatment of a diverse type of cancers. Oxidative stress is one of the most important side effects limiting the use of cisplatin. The protective effects of methanolic extract (ME) and ephedrine (EP), major compound, of Ephedra alata on CP-induced damages were here assessed. Treatment with CP-induced nephrotoxicity and hepatotoxicity characterized by biochemical alterations. In fact, using CP reduced significantly glutathione (GSH) levels, enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and increased malondialdehyde (MDA) content. Nonetheless, CP-treatment induced DNA damage at renal, hepatic, and blood cells and increased interferon gamma (IFNγ) level in serum. Co-treatments of mice with ME normalized relative kidney/body weight, restored biochemical and oxidative stress parameters, reduced DNA damage and IFNγ level. In conclusion, ME exhibited the best protective effect against CP damage compared with ephedrine. This is could be attributed to the presence of polysaccharides, organic acids, flavonoids, and tannins in addition to ephedrine alkaloids. These compounds were reported to play a major role in inhibiting and scavenging free radicals, providing an effective protection against CP- induced oxidative damage. Graphical abstract.

This study aimed to determine phytochemical contents, antibacterial properties, and antibiotic modulating potential of Punica granatum leaf extracts: hexane, chloroform, ethyl acetate, ethanol, and aqueous extracts as well as an extract enriched with total oligomer flavonoids (TOFs). The TOF extract contained the highest value of phenols and flavonoids. Rutin, luteolin, gallic acid, and ellagic acid were determined by HPLC analysis of this extract. The antibacterial activity was assayed by the disc diffusion method and microdilution method against Staphylococcus aureus and Escherichia coli standard ATCC strains and clinical isolates resistant strains. The TOF extract was the most active against all tested strains. The checkerboard method was used for the determination of synergy between two antibiotics (amoxicillin and cefotaxime) and P. granatum leaf extracts. The best synergistic interaction was found with TOF extract combined with amoxicillin for penicillin-resistant E. coli and penicillin-resistant S. aureus . These results can be assigned to tannins, flavonoids, and phenolic acids found in P. granatum leaf extracts. Pomegranate leaf extracts or active compounds isolated from these extracts could be used to fight the emergence and spread of resistant bacterial strains., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Amine Trabelsi et al.)