Etude phytochimique de quelques plantes extrêmophiles tunisiennes et exploration de leurs activités biologiques

Research strategies of active natural products include ecological approaches. Extremophile plants, and in particular, halophytes and xerophytes, salt and drought-resistant plants, are a case in point. As they develop an arsenal of adaptation responses, including a powerful antioxidant system, they prove to be a promising source of biomolecules, especially in phenolic compounds. In this study, an assessment of biological activities was carried out on eight Tunisian halophyte and xerophyte plants that would offer new applications in public health-care, as well as in agriculture. Limonium virgatum (Willd.) Fourr. (Plumbaginaceae), a halophyte plant, showed interesting antioxidant and antibacterial activities in accordance to a high polyphenol content and to the presence of phenylpropanoides, respectively. Cirsium scabrum (Poir.) Bonnet & Barratte (Asteraceae), a xerophyte plant, revealed a cytotoxic potential involving cycloartane-type triterpenes, and a promising activity against Dermabacter hominis strains which is linked to the presence of glycosylated flavones. Juncus maritimus Lam. (Juncaceae), a halophyte plant, should be referred to a source of phenanthrene derivativeswith original biological activities. Juncunol showed a high activity against an amoxicillin-resistant strain of Streptococcus pyogenes. Effusol was highly active against the wheat pathogen (Zymoseptoria tritici), for which high salinity conditions would stimulate its activity in the rhizomes of the plant. Most interestingly, dehydrojuncusol, has been introduced as a novel inhibitor of hepatitis C virus replication that is effective against resistant mutants for which some treatments available on the market became ineffective.L'approche écologique est une des stratégies de recherche de substances actives. Cette approche porte sur les plantes extrêmophiles, incluant les plantes halophytes et xérophytes, végétaux natifs des biotopes salins et arides. De par leur capacité à subsister dans un environnement contraignant, qui se traduit, entre autres, par l'acquisition d'un système antioxydant puissant, elles se révèlent être des réservoirs en biomolécules, notamment en composés phénoliques. Dans cette étude, nous nous sommes ainsi intéressés à huit plantes halophytes et xérophytes Tunisiennes pouvant avoir des activités biologiques en santé humaine et en santé du végétal. Limonium virgatum (Willd.) Fourr. (Plumbaginaceae), plante halophyte, a montré des activités antioxydantes et antibactériennes intéressantes qui se trouvent respectivement liées à un contenu en polyphénols élevé et à la présence de phénylpropanoïdes. Cirsium scabrum (Poir.) Bonnet & Barratte (Asteraceae), plante xérophyte, a montré une activité cytotoxique selective envers la lignée cancéreuse J774 mettant en avant l'efficacité de triterpènes de type cycloartane ; mais également un pouvoir antibactérien sur des souches de Dermabacter hominis, qui serait lié à la présence de flavones glycosylées. Juncus maritimus Lam. (Juncaceae), plante halophyte, s'est montrée être une source de dérivés phénanthréniques à activités originales. Le juncunol, a montré une activité prometteuse sur une souche de Streptococcus pyogenes résistante à l'amoxicilline. L'effusol actif sur le pathogène de la septoriose du blé (Zymoseptoria tritici), serait stimulé dans les rhizomes de la plante en conditions de salinité élevées. Enfin, le dehydrojuncusol s'est montré être un nouvel inhibiteur de la réplication du virus de l'hépatite C, capable d'agir sur des formes de résistance à certains traitement disponibles sur le marché

Phytochimie study of some Tunisian extremophilic plants and exploration of their biological activities

L'approche écologique est une des stratégies de recherche de substances actives. Cette approche porte sur les plantes extrêmophiles, incluant les plantes halophytes et xérophytes, végétaux natifs des biotopes salins et arides. De par leur capacité à subsister dans un environnement contraignant, qui se traduit, entre autres, par l'acquisition d'un système antioxydant puissant, elles se révèlent être des réservoirs en biomolécules, notamment en composés phénoliques. Dans cette étude, nous nous sommes ainsi intéressés à huit plantes halophytes et xérophytes Tunisiennes pouvant avoir des activités biologiques en santé humaine et en santé du végétal. Limonium virgatum (Willd.) Fourr. (Plumbaginaceae), plante halophyte, a montré des activités antioxydantes et antibactériennes intéressantes qui se trouvent respectivement liées à un contenu en polyphénols élevé et à la présence de phénylpropanoïdes. Cirsium scabrum (Poir.) Bonnet & Barratte (Asteraceae), plante xérophyte, a montré une activité cytotoxique selective envers la lignée cancéreuse J774 mettant en avant l'efficacité de triterpènes de type cycloartane ; mais également un pouvoir antibactérien sur des souches de Dermabacter hominis, qui serait lié à la présence de flavones glycosylées. Juncus maritimus Lam. (Juncaceae), plante halophyte, s'est montrée être une source de dérivés phénanthréniques à activités originales. Le juncunol, a montré une activité prometteuse sur une souche de Streptococcus pyogenes résistante à l'amoxicilline. L'effusol actif sur le pathogène de la septoriose du blé (Zymoseptoria tritici), serait stimulé dans les rhizomes de la plante en conditions de salinité élevées. Enfin, le dehydrojuncusol s'est montré être un nouvel inhibiteur de la réplication du virus de l'hépatite C, capable d'agir sur des formes de résistance à certains traitement disponibles sur le marché.Research strategies of active natural products include ecological approaches. Extremophile plants, and in particular, halophytes and xerophytes, salt and drought-resistant plants, are a case in point. As they develop an arsenal of adaptation responses, including a powerful antioxidant system, they prove to be a promising source of biomolecules, especially in phenolic compounds. In this study, an assessment of biological activities was carried out on eight Tunisian halophyte and xerophyte plants that would offer new applications in public health-care, as well as in agriculture. Limonium virgatum (Willd.) Fourr. (Plumbaginaceae), a halophyte plant, showed interesting antioxidant and antibacterial activities in accordance to a high polyphenol content and to the presence of phenylpropanoides, respectively. Cirsium scabrum (Poir.) Bonnet & Barratte (Asteraceae), a xerophyte plant, revealed a cytotoxic potential involving cycloartane-type triterpenes, and a promising activity against Dermabacter hominis strains which is linked to the presence of glycosylated flavones. Juncus maritimus Lam. (Juncaceae), a halophyte plant, should be referred to a source of phenanthrene derivativeswith original biological activities. Juncunol showed a high activity against an amoxicillin-resistant strain of Streptococcus pyogenes. Effusol was highly active against the wheat pathogen (Zymoseptoria tritici), for which high salinity conditions would stimulate its activity in the rhizomes of the plant. Most interestingly, dehydrojuncusol, has been introduced as a novel inhibitor of hepatitis C virus replication that is effective against resistant mutants for which some treatments available on the market became ineffective

Biocontrol activity of effusol from the extremophile plant, Juncus maritimus, against the wheat pathogen zymoseptoria tritici

National audienceZymoseptoria tritici, responsible for Septoria tritici blotch, is the most important pathogen of wheat. The control of this parasite relies mainly on synthetic fungicides, but their use is increasingly controversial and searching for alternative management strategies is encouraged. In this context, the biocontrol potential of crude methanolic extracts of eight extremophile plant species from Tunisia, including three xerophytes and five halophytes, against Z. tritici was assessed. Only the extract of Juncus maritimus rhizomes showed significant in vitro antifungal activity. In extremophile plants, the production of secondary metabolites is often influenced by abiotic conditions. Thus, we collected several samples of J. maritimus rhizomes at different vegetative stages, at different periods, and from different substrates to compare their antifungal activities. Our results suggest that the plant environment, especially the substrate of the soil, should be taken into account to identify great sources of natural antifungal products. From the most active sample, a 9,10-dehydrophenanthrene derivative, effusol, absent from other J. maritimus rhizomes extracts, was purified. This product showed a strong antifungal activity against the pathogen, with a minimal inhibitory concentration of 19gmL(-1) and an half-maximal inhibitory concentration of 9.98gmL(-1). This phenanthrene derivative could be a promising biocontrol molecule against Z. tritici

Antiproliferative and Antibacterial Activities of Cirsium scabrum from Tunisia.

Several Cirsium species are known for their uses in traditional medicine and consequently are studied for their phytochemical content and their biological activities. In the framework of a previous study conducted on eight extremophile plants from Tunisia, we highlighted that the crude methanolic extract of C. scabrum, a not investigated thistle, showed moderate but quite selective cytotoxic activity against the cancerous cell line J774 compared to the noncancerous cell line WI38 (IC50 = 11.53 μg/ml on J774, IC50 = 29.89 µg/ml on WI38, and selectivity index = 2.6). In the current study, the partitions of the leaves of C. scabrum were analyzed for their antiproliferative activity on the same cell lines. From the most active petroleum ether partition, we isolated four triterpenoids including lupeol, taraxasterol acetate, and a (1 : 1) mixture of 25-hydroperoxycycloart-23-en-3β-ol and 24-hydroperoxycycloart-25-en-3β-ol. These two cycloartane-type triterpenoids are mostly responsible for this cytotoxic activity. On the other hand, the antimicrobial potential of this plant was also evaluated against 36 microorganisms. The moderate antibacterial activity against 6 Staphylococcus aureus and 2 Dermabacter hominis strains is mainly attributed to the butanol partition whose major compounds are glycosides of flavones

Dehydrojuncusol, a Natural Phenanthrene Compound Extracted from Juncus maritimus Is a New Inhibitor of Hepatitis C Virus RNA Replication

International audienceRecent emergence of direct-acting antivirals (DAAs) targeting hepatitis C virus (HCV) proteins has considerably enhanced the success of antiviral therapy. However, the appearance of DAA-resistant-associated variants is a cause of treatment failure, and the high cost of DAAs renders the therapy not accessible in countries with inadequate medical infrastructures. Therefore, the search for new inhibitors with a lower cost of production should be pursued. In this context, the crude extract of Juncus maritimus Lam. was shown to exhibit high antiviral activity against HCV in cell culture. Bio-guided fractionation allowed the isolation and identification of the active compound, dehydrojuncusol. A time-of-addition assay showed that dehydrojuncusol significantly inhibited HCV infection when added after virus inoculation of HCV genotype 2a (50% effective concentration [EC50] = 1.35 µM). This antiviral activity was confirmed with an HCV subgenomic replicon, and no effect on HCV pseudoparticle entry was observed. Antiviral activity of dehydrojuncusol was also demonstrated in primary human hepatocytes. No in vitro toxicity was observed at active concentrations. Dehydrojuncusol is also efficient on HCV genotype 3a and can be used in combination with sofosbuvir. Interestingly, dehydrojuncusol was able to inhibit RNA replication of two frequent daclatasvir-resistant mutants (L31M or Y93H in NS5A). Finally, mutants resistant to dehydrojuncusol were obtained and showed that the HCV NS5A protein is the target of the molecule. In conclusion, dehydrojuncusol, a natural compound extracted from J. maritimus, inhibits infection of different HCV genotypes by targeting the NS5A protein and is active against resistant HCV variants frequently found in patients with treatment failure.IMPORTANCE Tens of millions of people are infected with hepatitis C virus (HCV) worldwide. Recently marketed direct-acting antivirals (DAAs) targeting HCV proteins have enhanced the efficacy of treatment. However, due to its high cost, this new therapy is not accessible to the vast majority of infected patients. Furthermore, treatment failures have also been reported due to the appearance of viral resistance. Here, we report on the identification of a new HCV inhibitor, dehydrojuncusol, that targets HCV NS5A and is able to inhibit RNA replication of replicons harboring resistance mutations to anti-NS5A DAAs used in current therapy. Dehydrojuncusol is a natural compound isolated from Juncus maritimus, a halophilic plant species that is very common in coastlines worldwide. This molecule might serve as a lead for the development of a new therapy that is more accessible to hepatitis C patients in the futur

Luteolin Isolated from Juncus acutus L., a Potential Remedy for Human Coronavirus 229E

International audienceThe COVID-19 pandemic, caused by SARS-CoV-2, addressed the lack of specific antiviral drugs against coronaviruses. In this study, bioguided fractionation performed on both ethyl acetate and aqueous sub-extracts of Juncus acutus stems led to identifying luteolin as a highly active antiviral molecule against human coronavirus HCoV-229E. The apolar sub-extract (CH2Cl2) containing phenanthrene derivatives did not show antiviral activity against this coronavirus. Infection tests on Huh-7 cells, expressing or not the cellular protease TMPRSS2, using luciferase reporter virus HCoV-229E-Luc showed that luteolin exhibited a dose-dependent inhibition of infection. Respective IC50 values of 1.77 µM and 1.95 µM were determined. Under its glycosylated form (luteolin-7-O-glucoside), luteolin was inactive against HCoV-229E. Time of addition assay showed that utmost anti-HCoV-229E activity of luteolin was achieved when added at the post-inoculation step, indicating that luteolin acts as an inhibitor of the replication step of HCoV-229E. Unfortunately, no obvious antiviral activity for luteolin was found against SARS-CoV-2 and MERS-CoV in this study. In conclusion, luteolin isolated from Juncus acutus is a new inhibitor of alphacoronavirus HCoV-229E

An ecological approach to discover new bioactive extracts and products: the case of extremophile plants

Eight extremophile plants from Tunisia were screened to find natural products with benefits in human health. These plants were collected in different areas in Tunisia. Their methanolic extracts were evaluated for their total phenolic content and for their antiradical (DPPH), antimicrobial (on 35 bacteria and one yeast), antiviral (hepatitis C virus, HCV) and cytotoxic activity (against WI38 and J774 cell lines). The most active species were subjected to a bioguided fractionation. The screening revealed promising activity for four plants, but two species have both antiradical and antimicrobial activity: Juncus maritimus and Limonium virgatum. The rhizomes extract of J. maritimus showed the highest activity against HCV, a selective antibacterial activity against Streptococcus dysgalactiae, and a moderate antiradical activity which is due to luteolin isolated in one step by centrifugal partition chromatography. The stems' and leaves' extracts of L. virgatum were rich in polyphenols responsible for the antiradical activity. Also, Limonium extracts showed an antibacterial activity with a broad spectrum. Extremophile plants have proven to be a promising source for bioactive metabolites. They have a powerful antioxidant system highly influenced by biotic and abiotic factors and the ability to produce secondary metabolites with antimicrobial activity

Stilbenoid Profiles of Canes from <i>Vitis</i> and <i>Muscadinia</i> Species

We present stilbenoid profiles of canes from 16 grapevines. Fifteen stilbenoids were obtained through isolation and structure identification using MS, NMR, and [α]_D or as commercial standards. An HPLC–UV method for the simultaneous quantification of nine of these stilbenoids was developed and applied to canes of <i>Vitis amurensis</i>, <i>Vitis arizonica</i>, <i>Vitis berlandieri</i>, <i>Vitis betulifolia</i>, <i>Vitis cinerea</i>, <i>Vitis</i> × <i>champini</i>, <i>Vitis</i> × <i>doaniana</i>, <i>Vitis labrusca</i>, <i>Vitis candicans</i> (syn. <i>Vitis mustangensis</i>), <i>Vitis riparia</i>, <i>Vitis rupestris</i>, <i>Vitis vinifera</i>, <i>Muscadinia rotundifolia</i>, and a <i>V. vinifera</i> × <i>M</i>. <i>rotundifolia</i> hybrid. In these species, <i>E</i>-ampelopsin E, <i>E</i>-amurensin B, <i>E</i>-piceid, <i>E</i>-piceatannol, <i>E</i>-resveratrol, <i>E</i>-resveratroloside, <i>E</i>-ε-viniferin, <i>E</i>-ω-viniferin, and <i>E</i>-vitisin B were quantified, when found in sufficient amounts. Total concentrations ranged from ∼2.2 to 19.5 g/kg of dry weight. Additional stilbenoids, <i>E</i>-3,5,4′-trihydroxystilbene 2-<i>C</i>-glucoside, <i>Z</i>-ampelopsin E, <i>Z</i>-<i>trans</i>-miyabenol C, <i>E</i>-<i>trans</i>-miyabenol C, scirpusin A, and <i>Z</i>-vitisin B, were identified but not quantified. Our results indicate that canes, particularly those of non-<i>vinifera</i> species, have substantial quantities of valuable, health-promoting stilbenoids