The Interplay of Sulfur and Selenium Enabling Variations in Micronutrient Accumulation in Red Spinach.

Aside from its importance in human and animal health, low levels of foliar-applied selenate (SeO4) can be advantageous in the presence of sulfur (S), contributing to improved growth, nutrient uptake, and crop quality. A hydroponic experiment in a growth chamber explored the interactive influence of Se and S on micronutrients and several quality indices, such as soluble sugars, organic acids, and total protein concentrations in spinach (Spinacia oleracea L.). Three levels of S (deprivation, adequate, and excessive) with varying quantities of Se (deficient, moderate, and higher) were examined in combination. Under S starvation and along with S nourishment in plant parts, Se treatments were found to cause noticeable variations in plant biomass and the concentrations of the examined elements and other quality parameters. Both Se levels promoted S accumulation in S-treated plants. Although the Se treatment had the opposite effect in shoots, it had a favorable impact on minerals (apart from Mn) in roots grown under S-limiting conditions. The S and Se relationship highlighted beneficial and/or synergistic effects for Mn and Fe in edible spinach portions. Reducing sugars were synergistically boosted by adequate S and moderate Se levels in roots, while in shoots, they were accumulated under moderate-or-higher Se and excessive S. Furthermore, the concentration of the quantified organic acids under S-deficient conditions was aided by various Se levels. In roots, moderate Se under high S application enhanced both malic acid and citric acid, while in the edible parts, higher Se under both adequate and elevated S levels were found to be advantageous in malic acid accumulation. Moreover, by elevating S levels in plant tissues, total protein concentration increased, whereas both moderate and high Se levels (Se1 and Se2) did not alter total protein accumulation in high S-applied roots and shoots. Our findings show that the high S and medium Se dose together benefit nutrient uptake; additionally, their combinations support soluble sugars and organic acids accumulation, contributing ultimately to the nutritional quality of spinach plants. Moreover, consuming 100 g of fresh red spinach shoot enriched with different Se and S levels can contribute to humans' daily micronutrients intake.

LC-ESI-MS/MS Analysis of Sulfolipids and Galactolipids in Green and Red Lettuce (Lactuca sativa L.) as Influenced by Sulfur Nutrition.

Sulfur (S) deprivation leads to abiotic stress in plants. This can have a significant impact on membrane lipids, illustrated by a change in either the lipid class and/or the fatty acid distribution. Three different levels of S (deprivation, adequate, and excess) in the form of potassium sulfate were used to identify individual thylakoid membrane lipids, which might act as markers in S nutrition (especially under stress conditions). The thylakoid membrane consists of the three glycolipid classes: monogalactosyl- (MGDG), digalactosyl- (DGDG), and sulfoquinovosyl diacylglycerols (SQDG). All of them have two fatty acids linked, differing in chain length and degree of saturation. LC-ESI-MS/MS served as a powerful method to identify trends in the change in individual lipids and to understand strategies of the plant responding to stress. Being a good model plant, but also one of the most important fresh-cut vegetables in the world, lettuce (Lactuca sativa L.) has already been shown to respond significantly to different states of sulfur supply. The results showed a transformation of the glycolipids in lettuce plants and trends towards a higher degree of saturation of the lipids and an increased level of oxidized SQDG under S-limiting conditions. Changes in individual MGDG, DGDG, and oxidized SQDG were associated to S-related stress for the first time. Promisingly, oxidized SQDG might even serve as markers for further abiotic stress factors.

Silicon-Selenium Interplay Imparts Cadmium Resistance in Wheat through an Up-Regulating Antioxidant System.

Cadmium (Cd), being a highly toxic heavy metal, significantly impacts plant growth and development by altering nutrient uptake and causing oxidative and structural damage, resulting in reduced yield. To combat Cd toxicity and accumulation in wheat, it was hypothesized that co-application of Selenium (Se) and Silicon (Si) can reduce the adverse effect of Cd and regulate Cd resistance while improving Se fortification in wheat. Therefore, this study evaluated the comparative effect of Se and Si on the growth and antioxidant defense systems of wheat plants grown in a hydroponic setup. Briefly, the plants were acclimatized to the hydroponic solution for 1 week and then exposed to 10 µmol Cd. Afterwards, the treatments, including 0.2 mmol Si and 1.5 µmol Se, were applied as a root and foliar application, respectively. Plants supplemented with both Se and Si showed improved biomass and other physiological growth attributes, and this response was associated with improved activity/contents of antioxidants, including glutathione (GSH) content, glutathione reductase (GR), ascorbate peroxidase (APX), and catalase (CAT), with related lowering of hydrogen peroxide, malondialdehyde content, and structural damages. Moreover, by Se + Si supplementation, a decrease in total S levels in plant tissues was observed, whereas an increase in total protein concentration and GSH indicated a different and novel mechanism of Cd tolerance and S homeostasis in the plant. It was observed that Si was more involved in significantly reducing Cd translocation by stabilizing Cd in the root and reducing its content in the soluble fraction in both the root and shoot. Whereas Se was found to play the main role in reducing the oxidative damage caused by Cd, and the effect was more profound in the shoot. In addition, this study also observed a positive correlation between Si and Se for relative uptake, which had not been reported earlier. Our findings show that the Se and Si doses together benefit growth regulation and nutrient uptake; additionally, their combinations support the Cd resistance mechanism in wheat through upregulation of the antioxidant system and control of Cd translocation and subcellular distribution, ultimately contributing to the nutritional quality of wheat produced. Thus, it is concluded that the co-application of Se and Si has improved the nutritional quality while reducing the Cd risk in wheat and therefore needs to be employed as a potential strategy to ensure food safety in a Cd-contaminated environment.

Secondary Metabolite Profile and Pharmacological Opportunities of Lettuce Plants following Selenium and Sulfur Enhancement.

Selenium (Se) is an essential trace nutrient for humans and animals owing to its role in redox regulation, thyroid hormone control factors, immunity, inflammatory reactions, brain activities, and carbohydrate regulation. It is also important to support muscle development, as well as for reproductive and cardiovascular well-being. Furthermore, sulfur is known to be a healing element, due to the remarkable function of specialized and secondary S-containing compounds. The scope of the current study was to determine the impact of Se and S enrichment on the secondary metabolite accumulation and antibacterial and NO inhibition activities in green and red leaf lettuce (V1 and V2, respectively). The plants were grown in a hydroponic system supplied with different S concentrations (S0: 0, S1: 1 mM and S2: 1.5 mM K2SO4) via the nutrient solution and foliar-applied varying levels of Se (0, 0.2 and 2.6 µM). Electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) combined with ultra-performance liquid chromatography (UPLC) was used to identify the secondary metabolites in green and red lettuce. The results indicated that extracts of the biofortified lettuce were not cytotoxic to Vero kidney cells at the highest concentration tested of 1 mg/mL. The ESI/MS of the tentatively identified metabolites showed that the response values of 5-O-caffeoylquinic acid, cyanidin 3-O-galactoside, quercetin 3-O-(6''-acetyl-glucoside) and quercetin 3-O-malonylglucoside were induced synergistically under higher Se and S levels in red lettuce plants. The acetone extract of red lettuce had antibacterial activity against Pseudomonas aeruginosa, with a minimum inhibitory concentration (MIC) of 0.156 and 0.625 µg/mL under S2/Se1 and S2/Se2 treatments, respectively. As with antibacterial activity, the acetone extract of green (V1) lettuce treated with adequate (S1) and higher S (S2) under Se-limiting conditions showed the ability to inhibit nitric oxide (NO) release from macrophages. NO production by macrophages was inhibited by 50% at respective concentrations of 106.1 ± 2.4 and 101.0 ± 0.6 µg/mL with no toxic effect on the cells, in response to S1 and S2, respectively, under Se-deficient conditions (Se0). Furthermore, the red cultivar (V2) exhibited the same effect as the green cultivar (V1) regarding NO inhibition, with IC50 = 113.0 ± 4.2 µg/mL, in response to S1/Se2 treatments. Collectively, the promising NO inhibitory effect and antibacterial activity of red lettuce under the above-mentioned conditions might be attributed to the production of flavonoid glycosides and phenylpropanoic acid esters under the same condition. To the best of our knowledge, this is the first report to show the novel approach of the NO inhibitory effect of Se and S enrichment in food crops, as an indicator for the potential of Se and S as natural anti-inflammatory agents.

Alterations of Content and Composition of Individual Sulfolipids, and Change of Fatty Acids Profile of Galactolipids in Lettuce Plants (Lactuca sativa L.) Grown under Sulfur Nutrition.

Alterations of chloroplast membrane lipids might serve as indicators of eco-physiologically induced and plant nutrition-induced changes during plant growth. The change in the degree of fatty acid saturation in the membranes is in particular a strategy of plants to adapt to abiotic stress conditions. Green multi-leaf lettuce plants (Lactuca sativa L.) were subjected to three different sulfur (S) levels. Sulfoquinovosyl diacylglycerol derivatives (SQDG) might be affected by S nutrition. Therefore, the present study was conducted to investigate the impact of S fertilization on the content and composition of individual SQDG. In addition to a change in the SQDG composition, a general change in the total lipid composition of the chloroplast membrane was observed. A significant increase in total SQDG content and doubling of the galactolipid content and significant alterations of individual SQDG were observed at elevated levels of S fertilization. High levels of S supply demonstrated a clear trend of increasing total chloroplast lipid content and concentrations of linolenic acid, in addition to a further decline in palmitic acid. The study opens perspectives on S supply and its crucial role in the build-up of photosynthetic apparatus. Moreover, it emphasizes the role of S-containing compounds, including sulfolipids, in modulating physiological adjustment mechanisms to improve tolerance ability to various abiotic stresses in plants and, consequently, plant food quality.

Crosstalk between Selenium and Sulfur Is Associated with Changes in Primary Metabolism in Lettuce Plants Grown under Se and S Enrichment.

This study investigated the beneficial effects of selenium (Se) and sulfur (S) enrichment on the primary metabolism in butterhead lettuce. The plants were treated with three levels of Se via foliar application in the presence of two S levels in the nutrient solution under greenhouse conditions. The lettuce plants that were exposed to the lower selenate level (1.3 µM) in combination with the adequate and high S supplies (1 and 2 mM, respectively) accumulated 38.25 ± 0.38 µg Se g-1 DM and 47.98 ± 0.68 µg Se g-1 DM, respectively. However, a dramatic increase in the Se concentration (122.38 ± 5.07 µg Se g-1 DM, and 146.71 ± 5.43 µg Se g-1 DM, respectively) was observed in the lettuce heads that were exposed to the higher selenate foliar application (3.8 µM) in response to the varied sulfate concentrations (S1 and S2, respectively). Under higher Se and S supplies in the lettuce plants, the levels of organic acids, including malic acid and citric acid, decreased therein to 25.7 ± 0.5 and 3.9 ± 0.3 mg g-1 DM, respectively, whereas, in the plants that were subjected to adequate S and lower Se fertilization, the malic acid, and citric acid levels significantly increased to 47.3 ± 0.4 and 11.8 ± 0.4 mg g-1 DM, respectively. The two Se levels (1.3 and 3.8 µM) under the S1 conditions also showed higher concentrations of water-soluble sugars, including glucose and fructose (70.8.4 ± 1.1 and 115.0 ± 2.1 mg g-1 DM; and 109.4 ± 2.1 and 161.1 ± 1.0 mg g-1 DM, respectively), compared to the control. As with the glucose and fructose, the amino acids (Asn, Glu, and Gln) exhibited strikingly higher levels (48.7 ± 1.1 µmol g-1 DM) under higher S and Se conditions. The results presented in this report reveal that the "crosstalk" between Se and S exhibited a unique synergistic effect on the responses to the amino acids and the soluble sugar biosynthesis under Se and S enrichment. Additionally, the Se-and-S crosstalk could have an important implication on the final nutritional value and quality of lettuce plants.

Investigation of anthelmintic activity of the acetone extract and constituents of Typha capensis against animal parasitic Haemonchus contortus and free-living Caenorhabditis elegans.

This study aimed to determine in vitro anthelmintic activity of plant extracts of eleven plant species used traditionally in South Africa to treat various disorders including symptoms related to nematode infections, and to isolate bioactive compounds from the most active plant extract. Crude plant extracts were tested on different life-cycle stages of Haemonchus contortus. The cytotoxicity of the most active extracts, fractions and compounds was evaluated on Vero cells and the most potent extract, fractions and compounds were tested for their ability to kill the parasitic H. contortus and the free-living nematode Caenorhabditis elegans. Typha capensis acetone extract had the strongest egg hatching inhibitory effect with an EC50 of 184.94 µg/mL, and this extract also halted larval development of H. contortus with an EC50 of 83.30 µg/mL compared to the positive control (albendazole) with an EC50 of 2.66 µg/mL. Typha capensis crude extract and its butanol fraction had promising anthelmintic activity against both parasitic H. contortus and free-living C. elegans. Two compounds isolated from T. capensis, namely, isorhamnetin-3-O-ß-D-glucoside and isorhamnetin 3-O-rutinoside, had antioxidant activity with IC50 values of 3.16 µg/mL and 0.96 µg/mL respectively, and good anthelmintic activity against H. contortus with IC50 values of 55.61 µg/mL and 145.17 µg/mL respectively. Identification of bioactive compounds from the T. capensis crude extract supports development of this extract as a complementary or alternative treatment against haemonchosis. However, further research is necessary to confirm the anthelmintic efficacy of the plant, including in vivo studies.

Comparative Metabolite Profile, Biological Activity and Overall Quality of Three Lettuce (Lactuca sativa L., Asteraceae) Cultivars in Response to Sulfur Nutrition.

The main objective of the present study was to assess the effects of sulfur (S) nutrition on plant growth, overall quality, secondary metabolites, and antibacterial and radical scavenging activities of hydroponically grown lettuce cultivars. Three lettuce cultivars, namely, Pazmanea RZ (green butterhead, V1), Hawking RZ (green multi-leaf lettuce, V2), and Barlach RZ (red multi-leaf, V3) were subjected to two S-treatments in the form of magnesium sulfate (+S) or magnesium chloride (-S). Significant differences were observed under -S treatments, especially among V1 and V2 lettuce cultivars. These responses were reflected in the yield, levels of macro- and micro-nutrients, water-soluble sugars, and free inorganic anions. In comparison with the green cultivars (V1 and V2), the red-V3 cultivar revealed a greater acclimation to S starvation, as evidenced by relative higher plant growth. In contrast, the green cultivars showed higher capabilities in production and superior quality attributes under +S condition. As for secondary metabolites, sixteen compounds (e.g., sesquiterpene lactones, caffeoyl derivatives, caffeic acid hexose, 5-caffeoylquinic acid (5-OCQA), quercetin and luteolin glucoside derivatives) were annotated in all three cultivars with the aid of HPLC-DAD-MS-based untargeted metabolomics. Sesquiterpene lactone lactucin and anthocyanin cyanidin 3-O-galactoside were only detected in V1 and V3 cultivars, respectively. Based on the analyses, the V3 cultivar was the most potent radical scavenger, while V1 and V2 cultivars exhibited antibacterial activity against Staphylococcus aureus in response to S provision. Our study emphasizes the critical role of S nutrition in plant growth, acclimation, and nutritional quality. The judicious-S application can be adopted as a promising antimicrobial prototype for medical applications.

In vitro antibacterial activity of Loxostylis alata extracts and isolated compounds against Salmonella species.

BACKGROUND: Owing to antibiotic resistance, alternative antimicrobials from medicinal plants are receiving attention as leads for anti-infective agents. This study aimed to investigate selected tree species and their constituents for activity against bacterial foodborne pathogens, particularly Salmonella serovars. METHODS: Antibacterial activity of ten plant species was determined by serial microdilution against bacteria implicated in causing gastrointestinal ailments. Active compounds were isolated from Loxostylis alata using bioassay-guided fractionation. Antioxidant activity was determined using free-radical scavenging assays. Cytotoxicity and genotoxicity of the extracts was ascertained on Vero cells, and using the Ames assay respectively. RESULTS: Extracts had low to moderate MIC values from 0.04 to 2.5 mg/mL. Protorhus longifolia and Loxostylis alata were most active and L. alata had the highest selectivity index value (2.51) against Salmonella Typhimurium, as well as high antioxidant activity. Cytotoxicity values ranged from 0.02 to 0.47 mg/mL, while tested extracts were not genotoxic. Bioactive compounds isolated from L. alata included delicaflavone and a polymethoxyflavone. CONCLUSIONS: The Loxostylis alata leaf extract had strong activity against Salmonella serovars but isolated compounds were less active, indicating likely synergistic effects. Extracts of L. alata are promising candidates for development of antimicrobial preparations or food additives against microbial contamination.

Anti-influenza A virus activity of two Newtonia species and the isolated compound myricetin-3-o-rhamnoside.

BACKGROUND: Some viruses play a key role in the disturbance of the digestive system. The common viruses which cause infectious diarrhoea (gastroenteritis) include astrovirus, caliciviruses, coronavirus and torovirus which are single-stranded RNA viruses. Influenza A virus (H1N1) also causes diarrhoea in addition to being associated with respiratory symptoms. In preliminary studies, Newtonia hildebrandtii and N. buchananii leaf extracts had good antibacterial activity against some bacteria implicated in causing diarrhoea. The aim of this study was to evaluate the anti-influenza activity of two Newtonia species extracts and the isolated compound (myricitrin). METHODS: N. hildebrandtii and N. buchananii acetone, and MeOH: DCM (methanol-dichloromethane) leaf and stem extracts, and an antibacterial compound myricetin-3-o-rhamnoside (myricitrin), isolated from N. buchananii, were evaluated for their antiviral efficacy against influenza A virus (IAV) PR8/34/H1N1 as a model organism. The MTT and hemagglutination assays were used to assess the extracts and compound interference with cell viability and viral surface HA glycoprotein. The quantitative real-time PCR was performed to assess the viral load. RESULTS: Plant extracts of N. hildebrandtii and N. buchananii were effective against IAV. The extracts in combination with H1N1 showed highly significant antiviral activity (P < 0.01) and maintained cell viabilities (P < 0.05). Myricitrin was non-cytotoxic at concentration 104 µg/ml. Myricitrin was most effective against IAV in a co-penetration combined treatment, thereby confirming the inhibitory effect of this compound in the viral attachment and entry stages. Myricitrin treatment also resulted in the highest viability of the cells in co-penetration treatment. The activity of myricitrin indicates the potential of the extracts in controlling viral infection at the attachment stage. The antiviral effect of myricitrin on IAV load in MDCK cell culture was confirmed using quantitative real-time PCR. CONCLUSION: Data from this study support further research and development on Newtonia hildebrandtii, Newtonia buchananii and myricitrin to address diarrhoea and related conditions caused by viruses in both human and veterinary medicine. Further work needs to be conducted on the activity of the extracts and the purified compound on other viruses of importance which have similar symptoms to influenza virus such as the coronavirus which led to a recent global pandemic.

Regulation of Selenium/Sulfur Interactions to Enhance Chemopreventive Effects: Lessons to Learn from Brassicaceae.

Selenium (Se) is an essential trace element, which represents an integral part of glutathione peroxidase and other selenoproteins involved in the protection of cells against oxidative damage. Selenomethionine (SeMet), selenocysteine (SeCys), and methylselenocysteine (MeSeCys) are the forms of Se that occur in living systems. Se-containing compounds have been found to reduce carcinogenesis of animal models, and dietary supplemental Se might decrease cancer risk. Se is mainly taken up by plant roots in the form of selenate via high-affinity sulfate transporters. Consequently, owing to the chemical similarity between Se and sulfur (S), the availability of S plays a key role in Se accumulation owing to competition effects in absorption, translocation, and assimilation. Moreover, naturally occurring S-containing compounds have proven to exhibit anticancer potential, in addition to other bioactivities. Therefore, it is important to understand the interaction between Se and S, which depends on Se/S ratio in the plant or/and in the growth medium. Brassicaceae (also known as cabbage or mustard family) is an important family of flowering plants that are grown worldwide and have a vital role in agriculture and populations' health. In this review we discuss the distribution and further interactions between S and Se in Brassicaceae and provide several examples of Se or Se/S biofortifications' experiments in brassica vegetables that induced the chemopreventive effects of these crops by enhancing the production of Se- or/and S-containing natural compounds. Extensive further research is required to understand Se/S uptake, translocation, and assimilation and to investigate their potential role in producing anticancer drugs.

Inhibitory effect of Newtonia extracts and myricetin-3-o-rhamnoside (myricitrin) on bacterial biofilm formation.

BACKGROUND: Diarrhoea is a major health issue in both humans and animals and may be caused by bacterial, viral and fungal infections. Previous studies highlighted excellent activity of Newtonia buchananii and N. hildebrandtii leaf extracts against bacterial and fungal organisms related to diarrhoea-causing pathogens. The aim of this study was to isolate the compound(s) responsible for antimicrobial activity and to investigate efficacy of the extracts and purified compound against bacterial biofilms. METHODS: The acetone extract of N. buchananii leaf powder was separated by solvent-solvent partitioning into eight fractions, followed by bioassay-guided fractionation for isolation of antimicrobial compounds. Antibacterial activity testing was performed using a broth microdilution assay. The cytotoxicity was evaluated against Vero cells using a colorimetric MTT assay. A crystal violet method was employed to test the inhibitory effect of acetone, methanol: dichloromethane and water (cold and hot) extracts of N. buchananii and N. hildebrandtii leaves and the purified compound on biofilm formation of Pseudomonas aeruginosa, Escherichia coli, Salmonella Typhimurium, Enterococcus faecalis, Staphylococcus aureus and Bacillus cereus. RESULTS: Myricetin-3-o-rhamnoside (myricitrin) was isolated for the first time from N. buchananii. Myricitrin was active against B. cereus, E. coli and S. aureus (MIC = 62.5 µg/ml in all cases). Additionally, myricitrin had relatively low cytotoxicity with IC50 = 104 µg/ml. Extracts of both plant species had stronger biofilm inhibitory activity against Gram-positive than Gram-negative bacteria. The most sensitive bacterial strains were E. faecalis and S. aureus. The cold and hot water leaf extracts of N. buchananii had antibacterial activity and were relatively non-cytotoxic with selectivity index values of 1.98-11.44. CONCLUSIONS: The purified compound, myricitrin, contributed to the activity of N. buchananii but it is likely that synergistic effects play a role in the antibacterial and antibiofilm efficacy of the plant extract. The cold and hot water leaf extracts of N. buchananii may be developed as potential antibacterial and antibiofilm agents in the natural treatment of gastrointestinal disorders including diarrhoea in both human and veterinary medicine.

Flavonoids isolated from the South African weed Chromolaena odorata (Asteraceae) have pharmacological activity against uropathogens.

BACKGROUND: Urinary tract infections (UTIs) caused by opportunistic pathogens are among the leading health challenges globally. Most available treatment options are failing as a result of antibiotic resistance and adverse effects. Natural sources such as plants may serve as promising alternatives. METHODS: Compounds were isolated from the South African weed Chromolaena odorata through column chromatography. Purified compounds were tested for antimicrobial activity using the p-iodonitrotetrazolium chloride (INT) colorimetric method, against uropathogenic Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Aspergillus fumigatus and Cryptococcus neoformans. Anti-biofilm, anti-adhesion and metabolic inhibition activities were investigated against selected strains. Safety of the compounds was determined against Vero monkey kidney, C3A human liver and colon (Caco2) cells. RESULTS: Four compounds identified as pectolinaringenin (1), (±)-4',5,7-trimethoxy flavanone (2), 5-hydroxy-3,7,4'-trimethoxyflavone (3) and 3,5,7-trihydroxy-4'-methoxyflavone) (4) were isolated. Minimum inhibitory concentration (MIC) varied between 0.016 and 0.25 mg/mL. Compounds 2 and 3 showed promising antimicrobial activity against E. coli, S. aureus, K. pneumoniae, A. fumigatus and C. neoformans with MIC between 0.016 and 0.125 mg/mL, comparable to gentamicin, ciprofloxacin and amphotericin B used as positive controls. Compounds 2 and 3 showed good anti-biofilm and metabolic inhibition activities against E. coli and S. aureus but weak anti-adhesion activity against the organisms. Low toxicity with selectivity indexes between 1 and 12.625 were recorded with the compounds, indicating that the compounds were rather toxic to the microbial strains and not to the human and animal cells. CONCLUSION: Pharmacological activities displayed by compounds 2 and 3 isolated from C. odorata and low toxicity recorded credits it as a potential lead for the development of useful prophylactic treatments and anti-infective drugs against UTIs. Although known compounds, this is the first time these compounds have been isolated from the South African weed C. odorata and tested for antimicrobial, anti-biofilm, metabolic inhibition and anti-adhesion activities.

Potential Natural Products Against Respiratory Viruses: A Perspective to Develop Anti-COVID-19 Medicines.

The emergence of viral pneumonia caused by a novel coronavirus (CoV), known as the 2019 novel coronavirus (2019-nCoV), resulted in a contagious acute respiratory infectious disease in December 2019 in Wuhan, Hubei Province, China. Its alarmingly quick transmission to many countries across the world and a considerable percentage of morbidity and mortality made the World Health Organization recognize it as a pandemic on March 11, 2020. The perceived risk of infection has led many research groups to study COVID-19 from different aspects. In this literature review, the phylogenetics and taxonomy of COVID-19 coronavirus, epidemiology, and respiratory viruses similar to COVID-19 and their mode of action are documented in an approach to understand the behavior of the current virus. Moreover, we suggest targeting the receptors of SARS-CoV and SARS-CoV-2 such as ACE2 and other proteins including 3CLpro and PLpro for improving antiviral activity and immune response against COVID-19 disease. Additionally, since phytochemicals play an essential role in complementary therapies for viral infections, we summarized different bioactive natural products against the mentioned respiratory viruses with a focus on influenza A, SARS-CoV, MERS, and COVID-19.Based on current literature, 130 compounds have antiviral potential, and of these, 94 metabolites demonstrated bioactivity against coronaviruses. Interestingly, these are classified in different groups of natural products, including alkaloids, flavonoids, terpenoids, and others. Most of these compounds comprise flavonoid skeletons. Based on our survey, xanthoangelol E (88), isolated from Angelica keiskei (Miq.) Koidz showed inhibitory activity against SARS-CoV PLpro with the best IC50 value of 1.2 µM. Additionally, hispidulin (3), quercetin (6), rutin (8), saikosaponin D (36), glycyrrhizin (47), and hesperetin (55) had remarkable antiviral potential against different viral infections. Among these compounds, quercetin (6) exhibited antiviral activities against influenza A, SARS-CoV, and COVID-19 and this seems to be a highly promising compound. In addition, our report discusses the obstacles and future perspectives to highlight the importance of developing screening programs to investigate potential natural medicines against COVID-19.

The genus Tragopogon (Asteraceae): A review of its traditional uses, phytochemistry, and pharmacological properties.

ETHNOPHARMACOLOGICAL RELEVANCE: Species of Tragopogon are used in traditional medicine, and consumed as vegetables across the world. In terms of the medicinal uses of Tragopogon, different species have found use in traditional medicine, including uses for wound-healing, treatment of gastrointestinal and hepatic complaints, cancer, kidney and liver dysfunction, inflamed skin and certain cutaneous diseases, as well as constipation, fatigue and anoxia. AIM OF THE STUDY: The aim of this review is to highlight and critically summarize those species of the genus that have been studied as a source of interesting lead compounds, and their traditional uses and bioactivities. MATERIALS AND METHODS: A comprehensive and systematic review of literature on traditional uses, phytochemicals and pharmacological properties of the genus Tragopogon was carried out. Information was retrieved from secondary databases such as Scopus, Chemical Abstracts Services (Scifinder), Pubmed, Google Scholar and ScienceDirect, in addition to primary sources including books, PhD and MSc dissertations, and official websites. Species names were validated using "The Plant List" (www.theplantlist.org). RESULTS: The taxa of the genus Tragopogon are known for their local and traditional uses as medicine for treatment of various diseases, and have been consumed as vegetables and snacks for generations in Eurasia, the Mediterranean, Caucasus, Europe and North America. From the approximately 110 species of Tragopogon, only twelve species have been scientifically evaluated for their bioactivity and/or phytochemical composition. Tragopogon species are a rich source of phytochemical constituents and among those that have been identified are 19 flavonoids, 35 terpenoids, seven bibenzyl derivatives, five benzylphtalides, six stilbenes, nine dihydroisocoumarin derivatives, nine phenylmethane derivatives, three hydroxyphenylacetic acid derivatives, four phenylpropane derivatives, four esters of phenylpropanoic acids, a coumarin derivative, and a spermine derivative. Various extracts of the taxa, in addition to the isolated compounds, demonstrated pharmacological properties such as antitumor, antimicrobial, anti-inflammatory and enzyme inhibitory activities, in addition to hepatoprotective, antihyperlipidaemic and wound-healing properties. CONCLUSION: This review highlights the traditional uses, phytochemistry and pharmacological properties of the few studied taxa of the genus Tragopogon. Some of the reviewed papers were not of an appropriate methodological standard. For instance, phytochemical profiles were not determined, and the fundamental requirements of the pharmacological properties were not defined such as including appropriate positive and negative controls, and calculating the MIC values. Furthermore, these studies did not provide an in depth evaluation of bioactivity of the extracts and the isolated compounds or in vivo experiments which could indicate therapeutic relevance. From a phytopharmacological point of view, this review recommends more high quality evidence-based research on Tragopogon species for further development of plant-derived remedies and compounds.

Divergent metabolic adjustments in nodules are indispensable for efficient N2 fixation of soybean under phosphate stress.

The main objective of the present study was to characterize the symbiotic N2 fixation (SNF) capacity and to elucidate the underlying mechanisms for low-Pi acclimation in soybean plants grown in association with two Bradyrhizobium diazoefficiens strains which differ in SNF capacity (USDA110 vs. CB1809). In comparison with the USDA110-soybean, the CB1809-soybean association revealed a greater SNF capacity in response to Pi starvation, as evidenced by relative higher plant growth and higher expression levels of the nifHDK genes. This enhanced Pi acclimation was partially related to the efficient utilization to the overall carbon (C) budget of symbiosis in the CB1809-induced nodules compared with that of the USDA110-induced nodules under low-Pi provision. In contrast, the USDA110-induced nodules favored other metabolic acclimation mechanisms that expend substantial C cost, and consequently cause negative implications on nodule C expenditure during low-Pi conditions. Fatty acids, phytosterols and secondary metabolites are characterized among the metabolic pathways involved in nodule acclimation under Pi starvation. While USDA110-soybean association performed better under Pi sufficiency, it is very likely that the CB1809-soybean association is better acclimatized to cope with Pi deficiency owing to the more effective functional plasticity and lower C cost associated with these nodular metabolic arrangements.

Serologic Follow-up of Middle East Respiratory Syndrome Coronavirus Cases and Contacts-Abu Dhabi, United Arab Emirates.

Background: Although there is evidence of person-to-person transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in household and healthcare settings, more data are needed to describe and better understand the risk factors and transmission routes in both settings, as well as the extent to which disease severity affects transmission. Methods: A seroepidemiological investigation was conducted among MERS-CoV case patients (cases) and their household contacts to investigate transmission risk in Abu Dhabi, United Arab Emirates. Cases diagnosed between 1 January 2013 and 9 May 2014 and their household contacts were approached for enrollment. Demographic, clinical, and exposure history data were collected. Sera were screened by MERS-CoV nucleocapsid protein enzyme-linked immunosorbent assay and indirect immunofluorescence, with results confirmed by microneutralization assay. Results: Thirty-one of 34 (91%) case patients were asymptomatic or mildly symptomatic and did not require oxygen during hospitalization. MERS-CoV antibodies were detected in 13 of 24 (54%) case patients with available sera, including 1 severely symptomatic, 9 mildly symptomatic, and 3 asymptomatic case patients. No serologic evidence of MERS-CoV transmission was found among 105 household contacts with available sera. Conclusions: Transmission of MERS-CoV was not documented in this investigation of mostly asymptomatic and mildly symptomatic cases and their household contacts. These results have implications for clinical management of cases and formulation of isolation policies to reduce the risk of transmission.

Anti-inflammatory and antioxidant properties of leaf extracts of eleven South African medicinal plants used traditionally to treat inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammation is a complex mechanism employed by the body to promote healing and restoration to normal function in the event of injury. Eleven plant species were selected in this study based on their use in traditional medicine against inflammation in South Africa. METHODS: Hexane, acetone, ethanol, methanol and water extracts of the powdered plants were prepared and a total of fifty-five extracts were tested for their anti-inflammatory and antioxidant activities. The anti-inflammatory activity of extracts was evaluated via the 15-lipoxygenase (15-LOX) inhibitory and the nitric oxide (NO) inhibition assays using lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophages. Total flavonoid and total phenolic contents were determined. The antioxidant activity of the extracts was performed using radical scavenging DPPH (2, 2-diphenyl-1-picrylhydrazyl) and electron reducing ABTS (2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) assays. RESULTS: The hexane extract of Typha capensis (TC) had good lipoxygenase inhibitory activity with IC50 of 4.65 µg/mL, significantly (p < 0.05) higher than that of the positive control quercetin (IC50 = 24.60). The same extract also had good nitric oxide inhibitory activity with 86% NO inhibition and cell viability of 97% at 50 µg/mL. The TC acetone extract had the best antioxidant activity with IC50 of 7.11 and 1.91 µg/mL respectively in the DPPH and ABTS assays. Following fractionation of the TC plant material, the ethyl acetate fraction had interesting antioxidant activity and the methanol/water (35%) and hexane fractions had good 15-LOX inhibitory activity. The antioxidant and anti-inflammatory activities therefore resided in both polar and more non-polar fractions. CONCLUSION: The acetone extract of Typha capensis and its fractions had good anti-inflammatory and antioxidant activities, supporting the medicinal use of this species against inflammation. Other species including Ficus elastica, Carpobrotus edulis, Cotyledon orbiculata and Senna italica also had good activity worthy of further investigation.

A comprehensive study of the potential phytomedicinal use and toxicity of invasive Tithonia species in South Africa.

BACKGROUND: Tithonia diversifolia and T. rotundifolia belong to the Asteraceae family and are native to Mexico and Central America. These plants have become invasive in parts of tropical Africa and Asia where they have become an ecological, agricultural and economic burden. Tithonia diversifolia is exploited by locals in its native and most parts of its invasive range as a source of medicines; however, T. rotundifolia is only used for medicinal purposes in one country in the native range (Venezuela) and none in the invasive range. Although T. diversifolia has been studied for different biological activities, little or no attention has been given to T. rotundifolia. This study compared the antimicrobial activity, phytochemistry, identification of bioactive compound(s) and toxicity levels of different leaf extracts and fractions of T. diversifolia and T. rotundifolia. METHODS: Antimicrobial activity was evaluated against seven pathogenic bacteria, four non-pathogenic Mycobacterium species and three fungal species using serial microdilution assays. Phytochemical contents were determined through standard methods of analysis. UPLC/MS was used to analyse the fractions to identify possible bioactive compounds that may be responsible for bioactivity, while toxicity tests were carried out using the colorimetric MTT assay and the Ames test. RESULTS: Both species had a range of antimicrobial activity against bacterial, mycobacterial and fungal species. However, T. rotundifolia displayed better activity against most of the strains tested with minimum inhibitory concentration values ranging between 0.01 and 0.07 mg/ml. Both species were rich in phenolics, flavonoids and tannins. Tagitinin A was identified as the main compound present in both species, and this compound may be responsible for the antimicrobial activity displayed. Toxicity tests showed that T. diversifolia was cytotoxic at concentrations used in this study, while T. rotundifolia was not. Both species did not show any mutagenic/genotoxic effects. CONCLUSION: The above results suggest that both species may be further developed as a source of antimicrobials for the treatment of infections caused by opportunistic pathogens. They may also serve as alternatives to highly exploited plant species with the same medicinal properties. However, T. diversifolia should be used with caution as it may be toxic.

Natural Cyclic Peptides as an Attractive Modality for Therapeutics: A Mini Review.

Peptides are important biomolecules which facilitate the understanding of complex biological processes, which in turn could be serendipitous biological targets for future drugs. They are classified as a unique therapeutic niche and will play an important role as fascinating agents in the pharmaceutical landscape. Until now, more than 40 cyclic peptide drugs are currently in the market, and approximately one new cyclopeptide drug enters the market annually on average. Interestingly, the majority of clinically approved cyclic peptides are derived from natural sources, such as peptide antibiotics and human peptide hormones. In this report, the importance of cyclic peptides is discussed, and their role in drug discovery as interesting therapeutic biomolecules will be highlighted. Recently isolated naturally occurring cyclic peptides from microorganisms, sponges, and other sources with a wide range of pharmacological properties are reviewed herein.