The Anti-Candida Activity of Tephrosia apollinea Is More Superiorly Attributed to a Novel Steroidal Compound with Selective Targeting.

Tephrosia is widely distributed throughout tropical, subtropical, and arid regions. This genus is known for several biological activities, including its anti-Candida activity, which is mainly attributed to prenylated flavonoids. The biological activities of most Tephrosia species have been studied, except T. apollinea. This study was conducted to investigate the underlying anti-Candida activity of T. apollinea, wildly grown in the United Arab Emirates (UAE). The T. apollinea plant was collected, dried, and the leaves were separated. The leaves were ground and extracted. The dried extract was subjected to successive chromatography to identify unique phytochemicals with a special pharmacological activity. The activity of the compound was validated by homology modeling and molecular docking studies. A novel steroidal compound (ergosta-6, 8(14), 22, 24(28)-tetraen-3-one) was isolated and named TNS. In silico target identification of TNS revealed a high structural similarity with the Candida 14-α-demethylase enzyme substrate. The compound exhibited a significant anti-Candida activity, specifically against the multi-drug-resistant Candida auris at MIC50, 16 times less than the previously reported prenylated flavonoids and 5 times less than the methanol extract of the plant. These findings were supported by homology modeling and molecular docking studies. TNS may represent a new class of Candida 14-α-demethylase inhibitors.

Flavonoids are promising safe therapy against COVID-19.

Flavonoids are a class of phenolic natural products, well-identified in traditional and modern medicines in the treatment of several diseases including viral infection. Flavonoids showed potential inhibitory activity against coronaviruses including the current pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and designated as COVID-19. Here, we have collected all data related to the potential inhibitory mechanisms of flavonoids against SARS-CoV-2 infection and their significant immunomodulatory activities. The data were mapped and compared to elect major flavonoids with a promising role in the current pandemic. Further, we have linked the global existence of flavonoids in medicinal plants and their role in protection against COVID-19. Computational analysis predicted that flavonoids can exhibit potential inhibitory activity against SARS-CoV-2 by binding to essential viral targets required in virus entry and/ or replication. Flavonoids also showed excellent immunomodulatory and anti-inflammatory activities including the inhibition of various inflammatory cytokines. Further, flavonoids showed significant ability to reduce the exacerbation of COVID-19 in the case of obesity via promoting lipids metabolism. Moreover, flavonoids exhibit a high safety profile, suitable bioavailability, and no significant adverse effects. For instance, plants rich in flavonoids are globally distributed and can offer great protection from COVID-19. The data described in this study strongly highlighted that flavonoids particularly quercetin and luteolin can exhibit promising multi-target activity against SARS-CoV-2, which promote their use in the current and expected future outbreaks. Therefore, a regimen of flavonoid-rich plants can be recommended to supplement a sufficient amount of flavonoids for the protection and treatment from SARS-CoV-2 infection.

Lipid-based therapies against SARS-CoV-2 infection.

Viruses have evolved to manipulate host lipid metabolism to benefit their replication cycle. Enveloped viruses, including coronaviruses, use host lipids in various stages of the viral life cycle, particularly in the formation of replication compartments and envelopes. Host lipids are utilised by the virus in receptor binding, viral fusion and entry, as well as viral replication. Association of dyslipidaemia with the pathological development of Covid-19 raises the possibility that exploitation of host lipid metabolism might have therapeutic benefit against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, promising host lipid targets are discussed along with potential inhibitors. In addition, specific host lipids are involved in the inflammatory responses due to viral infection, so lipid supplementation represents another potential strategy to counteract the severity of viral infection. Furthermore, switching the lipid metabolism through a ketogenic diet is another potential way of limiting the effects of viral infection. Taken together, restricting the access of host lipids to the virus, either by using lipid inhibitors or supplementation with exogenous lipids, might significantly limit SARS-CoV-2 infection and/or severity.

Critical discovery and synthesis of novel antibacterial and resistance-modifying agents inspired by plant phytochemical defense mechanisms.

Antimicrobial resistance is at increasing risk worldwide since it is threatening the ability to control common infectious diseases, resulting in prolonged illness, disability, and death. Herein, we inspired by the effective plant phytochemical mechanisms evolved to overcome microbial pathogenesis and evolved resistance. Cuminaldehyde is previously reported as the main antibacterial component in Calligonum comosum essential oil. The toxicity of cuminaldehyde limits its medical application for human use. On the other hand, compared to cuminaldehyde, the plant total extract showed similar antibacterial activities, while maintained lower toxicity, although it contains 22 times less cuminaldehyde. Thus, we assumed that other components in the plant extracts specifically affect bacteria but not mammalian cells. Bioassay-guided fractionations combined with comparative metabolomics analysis of different plant extracts were employed. The results revealed the presence of bacterial species-specific phytochemicals. Cinnamyl linoleate and linoleic acid enhanced the antibacterial activities of cuminaldehyde and ampicillin against S. aureus including MRSA, while decanal and cinnamyl linoleate enhanced the activities against E. coli. Computational modeling and enzyme inhibition assays indicated that cinnamyl linoleate selectively bind to bacterial ribosomal RNA methyltransferase, an important enzyme involved in the virulence and resistance of multidrug resistant bacteria. The results obtained can be employed for the future preparation of pharmaceutical formula containing cinnamyl linoleate in order to overcome evolved multidrug resistance behaviors by microbes.

Lipophilic Metabolites and Anatomical Acclimatization of Cleome amblyocarpa in the Drought and Extra-Water Areas of the Arid Desert of UAE.

Plants adapt to different environmental conditions by developing structural and metabolic mechanisms. In this study, anatomical features and lipophilic metabolites were investigated in Cleome amblyocarpa Barr. & Murb., Cleomaceae plants growing in the arid desert of United Arab Emirates (UAE) in either low-water or extra-water areas, which were caused by the surrounding road run-off. The plant showed the presence of shaggy-like trichomes. The plant also developed special mechanisms to ensure its survival via release of lipophilic metabolites. The lipophilic metabolites, stained red with Sudan III, were apparently released by glandular trichomes and idioblasts of the shoot and roots, respectively. The identified lipophilic metabolites included those required for drought tolerance, protection against pathogens invasion, and detoxification. Plants growing in the low-water area caused an increase in the production of lipophilic metabolites-in particular, hydrocarbons and terpenoids. The lipophilic metabolites are known to provide the plant with unique waxy surfaces that reduce water loss and avoid penetration by pathogens. The release of lipid metabolites and the presence of shaggy-like trichomes represented unique features of the species that have never been reported. The provided chemical ecology information can be extended for several plant-related applications, particularly including drought tolerance.

Novel betulin derivative is responsible for the anticancer folk use of Ziziphus spina-christi from the hot environmental habitat of UAE.

ETHNOPHARMACOLOGICAL RELEVANCE: Several natural products derived from plant sources are developed to remarkable medicines based on their traditional uses. Ziziphus, a worldwide known plant, is proven for potential cytotoxic activity. However, the plant growing at the unique hot environmental climate of UAE was never investigated. Different phytochemicals may be produced from the same plant genotype at different climates leading to variable pharmacological activities. AIM OF THE STUDY: The study was conducted in order to investigate phytochemicals in the UAE native Z. spina-christi plant and its anticancer activity. MATERIALS AND METHODS: Z. spina-christi plant were collected, dried and dissected into leaves, stems and thorns. The plant organs were subjected to comparative fractionation-based anticancer assay followed by spectroscopic analysis of a uniquely isolated compound. RESULTS: The results indicate that a novel betulin derivative (13-dehydrobetulin) isolated from plant stem exhibited substantial anticancer activity specifically against liver cancer and with wide therapeutic range. CONCLUSIONS: Growth of cytotoxic traditionally-known plant remedy at harsh environmental habitat advances its anticancer activity due to production of novel phytochemical with optimum activity and minimal toxicity. Furthermore, such approach may be a future to develop novel lead compounds with optimum activity.

Mechanical and phytochemical protection mechanisms of Calligonum comosum in arid deserts.

Unlike animals, plants are sessile organisms, lacking circulating antibodies and specialized immune cells and are exposed to various harsh environmental conditions that make them at risk of being attacked by different pathogens and herbivores. Plants produce chemo-signals to respond to the surroundings and be able to distinguish between harmless and harmful signals. In this study, the production of phytochemicals as plant signaling mechanisms and their defensive roles in disease resistance and repelling herbivores are examined in Calligonum comosum. C. comosum is a leafless standalone perennial shrub widespread in sand dunes. The plant has the ability to survive the drastic environmental conditions of the arid/ hyperarid deserts of the Arabia. Structural anatomy and phytochemicals analyses were used to identify both mechanical and chemical defensive mechanisms in C. comosum. Microscopy-based investigations indicated that stems of this species developed hard structures in its outer layers including sclerenchyma and cluster crystals of calcium oxalate (CaOx). Sclerenchyma and CaOx are difficult to be eaten by herbivores and insects and can harm their mouthparts. On the other hand, the plant developed both short-distance (local) and long-distance (systematic over limited sphere) phytochemicals-producing cells located at its outer regions that is surrounding the inner nutrient-rich vascular system (VS). Local chemical was represented by phenolic idioblasts that were released in response to plant cutting. Systematic chemical was represented by toxic volatile oil containing ~50% benzaldehyde derivative (cuminaldehyde). The oil caused strong killing effect on both mammalian cells and microbial pathogens via either direct addition or indirect exposure to its vapor. The plants lost the oil content and allowed fungal growth once cut and dried. The localization of both defensive mechanisms to the outer region of the plant seemed to protect the inner nutrient-rich VS and hence maintained the plant survival. Surprisingly, in relation to traditional folklore use as medicine, local people use only green parts of the plant and only during the winter, where the plant found devoid of volatile oil and phenolic idioblasts. Moreover, it turns into recommendations for local people to avoid any health problems caused by the plant supply.

Plants' Natural Products as Alternative Promising Anti-Candida Drugs.

Candida is a serious life-threatening pathogen, particularly with immunocompromised patients. Candida infections are considered as a major cause of morbidity and mortality in a broad range of immunocompromised patients. Candida infections are common in hospitalized patients and elderly people. The difficulty to eradicate Candida infections is owing to its unique switch between yeast and hyphae forms and more likely to biofilm formations that render resistance to antifungal therapy. Plants are known sources of natural medicines. Several plants show significant anti-Candida activities and some of them have lower minimum inhibitory concentration, making them promising candidates for anti-Candida therapy. However, none of these plant products is marketed for anti-Candida therapy because of lack of sufficient information about their efficacy, toxicity, and kinetics. This review revises major plants that have been tested for anti-Candida activities with recommendations for further use of some of these plants for more investigation and in vivo testing including the use of nanostructure lipid system.

Exogenous and endogenous increase in fungal GGPP increased fungal Taxol production.

Taxol is an anticancer identified in both endophytic fungus and its host plant. Plant Taxol is a diterpenoid with geranylgeranyl diphosphate (GGPP) mediates the biosynthesis of its terpenoid moiety. Previous report has suggested that fungal Taxol may require terpenoid pathway for its biosynthesis. Here in this study, feeding a Taxol-producing endophytic fungus (Paraconiothyrium SSM001) with terpenoid precursors including isopentenyl pyrophosphate (IPP, isoprene) and GGPP enhanced Taxol production threefold and fivefold, respectively, compared to the control. Thus, we assumed that increasing the terpenoid pool size in particular GGPP by introducing a new copy number of GGPPS particularly from a Taxol-producing plant might increase the production level of fungal Taxol. Agrobacterium-mediated integration of Taxus canadensis geranylgeranyl diphosphate synthase (GGPPS) gene into the Paraconiothyrium SSM001 genome was successful and increased the terpenoid pool size indicated by an increase in carotenoid level and orange to red coloration of some GGPPS-transformed SSM001 colonies. Furthermore, the integration improved the level of Taxol production threefold. Feeding a GGPPS-transformed SSM001 fungus with a GGPP precursor increased the expression level of GGPPS transcript and Taxol production. The successful increase in both terpenoid and Taxol production levels due to GGPPS gene integration into the fungal genome might be a step forward in manipulating Taxol-producing endophytic fungi. Future control of the transformation time and the manipulation of the phenolic pathway could maximize the production level.

Assessment of herbal drugs for promising anti-Candida activity.

BACKGROUND: Microbial infections are diverse and cause serious human diseases. Candida albicans infections are serious healthcare-related infections that are complicated by its morphological switching from yeast to hyphae, resistant biofilm formation and mixed infections with bacteria. Due to the increase in drug resistance to currently used antimicrobial agents and the presence of undesirable side effects, the need for safe and effective novel therapies is important. Compounds derived from plants are known for their medicinal properties including antimicrobial activities. The purpose of the study was to compare and evaluate the anti-Candida activities of several medicinal plants in order for the selection of a herbal drug for human use as effective antimicrobial. The selection was taking into considerations two important parameters; parameters related to the selected drug including activity, stability, solubility and toxicity and parameters related to the pathogen including its different dynamic growth and its accompanied secondary bacterial infections. METHODS: Seven different plants including Avicennia marina (Qurm), Fagonia indica (Shoka'a), Lawsania inermis (Henna), Portulaca oleracea (Baq'lah), Salvadora persica (Souwak), Ziziphus spina- Christi (Sidr) and Asphodelus tenuifolius (Kufer) were ground and extracted with ethanol. The ethanol extracts were evaporated and the residual extract dissolved in water prior to testing against Candida albicans in its different morphologies. The antibacterial and cytotoxic effects of the plants extracts were also tested. RESULTS: Out of the seven tested plants, L. inermis and P. oleracea showed significant anti-Candida activity with MIC ~10 µg/mL. Furthermore, both plant extracts were able to inhibit C. albicans growth at its dynamic growth phases including biofilm formation and age resistance. Accompanied secondary bacterial infections can complicate Candida pathogenesis. L. inermis and P. oleracea extracts showed effective antibacterial activities against S. aureus, P. aeruginosa, E. coli, and the multidrug resistant (MDR) A. baumannii and Klebsiella pneumoniae. Both extracts showed no toxicity when measured at their MIC on human erythrocytes. CONCLUSION: The results from this study suggested that L. inermis and P. oleracea extracts and/or their chemicals are likely to be promising drugs for human use against C. albicans and MDR bacteria.

Seed colour affects light and temperature requirements during germination in two Lotus species (Fabaceae) of the Arabian subtropical deserts / El color de la semilla afecta los requerimientos de luz y temperatura durante la germinación en dos especies de Lotus (Fabaceae) de los desiertos subtropicales árabes

AbstractHeterogeneity in seeds mostly occurs due to physiological, environmental and genetic factors, and these could affect seed dormancy and germination. Therefore, the aim of our study was to assess the effect of seed colour on germination behavior. For this, both light and temperature requirements were assessed in Lotus glinoides and Lotus halophilus (Fabaceae) from the hyper-arid deserts of the United Arab Emirates. Germination was assessed in terms of both final germination level (percentage) and germination rate, as expressed by Timson’s germination velocity index. Lotus glinoides produces black and yellow-colored seeds, and L. halophilus produces green and yellow seeds. Different seed lots were germinated in both light and darkness at different temperatures. Yellow seeds of the two species attained significantly lower germination, compared to black and green seeds. There was no specific light or temperature requirements for the germination of the two coloured seeds of L. glinoides; the effect of interactions between seed colour and both light and incubation temperature, were not significant on the final germination percentage. in L. halophilus, green seeds germinated significantly more in both light and darkness at lower temperatures (15/25 °C) and in light at higher temperatures (25/35 °C), compared to yellow seeds. Yellow seeds germinated faster, compared to black at 15/25 °C in L. glinoides and compared to green seeds at 15/25 °C and 25/35 °C in L. halophilus. Seed colour variation, at least in L. halophilus, could be a survival strategy that would determine the time of germination throughout the year in the unpredictable desert environment. Rev. Biol. Trop. 64 (2): 483-492. Epub 2016 June 01.

ResumenLa heterogeneidad en las semillas se produce principalmente debido a factores fisiológicos, genéticos y ambientales, y esto podría afectar latencia de las semillas y la germinación. Por lo tanto, el objetivo de nuestro estudio fue evaluar el efecto del color de la semilla en el comportamiento de la germinación. Para ello, tanto los requisitos de luz y temperatura fueron evaluados en Lotus glinoides y Lotus halophilus (Fabaceae) desde los desiertos hiper-árida de los Emiratos Árabes Unidos. La germinación se evaluó en términos de nivel final de germinación (porcentaje) y la tasa de germinación, expresado por el índice de velocidad de germinación de Timson. L. glinoides produce semillas negro y de color amarillo, y L. halophilus produce semillas verdes y amarillas. Los diferentes lotes de semillas fueron germinadas en luz y oscuridad a diferentes temperaturas. Semillas amarillas de las dos especies alcanzaron significativamente menor germinación, en comparación con las semillas negras y verdes. No había requisitos específicos de luz o temperatura para la germinación de las semillas de dos colores de L. glinoides; el efecto de las interacciones entre color de la semilla y la luz y la temperatura de incubación, no fueron significativas en el porcentaje final de germinación. En L. halophilus, semillas verdes germinados significativamente más en la luz y la oscuridad a temperaturas más bajas (15/25 °C) ya la luz a temperaturas más altas (25/35 °C), en comparación con semillas amarillas. Semillas amarillas germinaron más rápido, en comparación con el negro a 15/25 °C en L. glinoides y en comparación con semillas verdes a 15/25 °C y 25/35 °C en L. halophilus. La variación del color de la semilla, al menos en L. halophilus, podría ser una estrategia de supervivencia que determinaría el momento de la germinación durante todo el año en el entorno del desierto impredecible.

Seed colour affects light and temperature requirements during germination in two Lotus species (Fabaceae) of the Arabian subtropical deserts.

Heterogeneity in seeds mostly occurs due to physiological, environmental and genetic factors, and these could affect seed dormancy and germination. Therefore, the aim of our study was to assess the effect of seed colour on germination behavior. For this, both light and temperature requirements were assessed in Lotus glinoides and Lotus halophilus (Fabaceae) from the hyper-arid deserts of the United Arab Emirates. Germination was assessed in terms of both final germination level (percentage) and germination rate, as expressed by Timson's germination velocity index. Lotus glinoides produces black and yellow-colored seeds, and L. halophilus produces green and yellow seeds. Different seed lots were germinated in both light and darkness at different temperatures. Yellow seeds of the two species attained significantly lower germination, compared to black and green seeds. There was no specific light or temperature requirements for the germination of the two coloured seeds of L. glinoides; the effect of interactions between seed colour and both light and incubation temperature, were not significant on the final germination percentage. In L. halophilus, green seeds germinated significantly more in both light and darkness at lower temperatures (15/25 °C) and in light at higher temperatures (25/35 °C), compared to yellow seeds. Yellow seeds germinated faster, compared to black at 15/25 °C in L. glinoides and compared to green seeds at 15/25 °C and 25/35 °C in L. halophilus. Seed colour variation, at least in L. halophilus, could be a survival strategy that would determine the time of germination throughout the year in the unpredictable desert environment.

Floral diversity in desert ecosystems: comparing field sampling to image analyses in assessing species cover.

BACKGROUND: Developing a quick and reliable technique to estimate floral cover in deserts will assist in monitoring and management. The present attempt was to estimate plant cover in the UAE desert using both digital photography and field sampling. Digital photographs were correlated with field data to estimate floral cover in moderately (Al-Maha) and heavily (DDCR) grazed areas. The Kruskal-Wallis test was also used to assess compatibility between the two techniques within and across grazing intensities and soil substrates. RESULTS: Results showed that photographs could be a reliable technique within the sand dune substrate under moderate grazing (r = 0.69). The results were very poorly correlated (r =-0.24) or even inversely proportional (r =-0.48) when performed within DDCR. Overall, Chi-square values for Al-Maha and DDCR were not significant at P > 0.05, indicating similarities between the two methods. At the soil type level, the Kruskal-Wallis analysis was not significant (P > 0.05), except for gravel plains (P < 0.05). Across grazing intensities and soil substrates, the two techniques were in agreement in ranking most plant species, except for Lycium shawii. CONCLUSIONS: Consequently, the present study has proven that digital photography could not be used reliably to asses floral cover, while further testing is required to support such claim. An image-based sampling approach of plant cover at the species level, across different grazing and substrate variations in desert ecosystems, has its uses, but results are to be cautiously interpreted.