Macaronesian Plants as Promising Biopesticides against the Crop Pest Ceratitis capitata.

Ceratitis capitata is responsible for significant economic losses in the fruit production industry, and the market lacks biopesticides that are effective but also cheaper and less contaminating, with fewer negative impacts on the environment. In this regard, the present study suggests as potential options ethanolic extracts from several Macaronesian plants, which inhibit the oviposition and are toxic to C. capitata, and whose preparation involve a non-toxic solvent (i.e., ethanol), low energy expenditure and cheap apparatus (i.e., maceration at room temperature). Among the evaluated species, the extracts of Hedychium gardnerianum, Cistus symphytifolius and Salvia canariensis are the most active (50 mg/mL), revealing an increase in C. capitata adults' mortality from 21.15% to 27.41% after 72 h, a value statistically identical to azadirachtin (25.93%) at the recommended concentration (0.88 mg/mL). Considering the quantity and biomass available to prepare a biopesticide in the future, and the level of activity, the ethanolic extract of H. gardnerianum was fractionated and each fraction tested. The water fraction at 50 mg/mL proved to be more effective than the original extract, both in terms of mortality (57.69%), with LT50 = 72.5 h, and oviposition deterrence (83.43%), values statistically higher than those obtained by azadirachtin at 0.88 mg/mL. Analysis of this fraction by HPLC-MS/MS showed that it is mainly composed of glycosylated derivatives of quercetin and myricetin in addition to some triterpenes. These findings highlight some Macaronesian species, and in particular, the more polar fraction of H. gardnerianum ethanolic extract, as promising and ecological alternatives to conventional insecticides, for use in the integrated management of the C. capitata pest.

Asparagopsis Genus: What We Really Know About Its Biological Activities and Chemical Composition.

Although the genus Asparagopsis includes only two taxonomically accepted species, the published literature is unanimous about the invasive nature of this genus in different regions of the globe, and about the availability of large amounts of biomass for which it is important to find a commercial application. This review shows that extracts from Asparagospsis species have already been evaluated for antioxidant, antibacterial, antifungal, antiviral, antifouling, cytotoxic, antimethanogenic and enzyme-inhibitory activity. However, the tables presented herein show, with few exceptions, that the activity level displayed is generally low when compared with positive controls. Studies involving pure compounds being identified in Asparagopsis species are rare. The chemical compositions of most of the evaluated extracts are unknown. At best, the families of the compounds present are suggested. This review also shows that the volatile halogenated compounds, fatty acids and sterols that are biosynthesized by the Asparagopsis species are relatively well known. Many other non-volatile metabolites (halogen compounds, flavonoids, other phenolic compounds) seem to be produced by these species, but their chemical structures and properties haven'been investigated. This shows how much remains to be investigated regarding the secondary-metabolite composition of these species, suggesting further studies following more targeted methodologies.

Bio-Guided Optimization of Cystoseira abies-marina Cosmeceuticals Extraction by Advanced Technologies.

Cystoseira abies-marina (reclassified as Gongolaria abies-marina) is a brown seaweed species rich in meroterpenoids, presenting interesting antioxidant, antitumor, and anti-inflammatory activities. However, there is still a lot to uncover regarding the bioactive potential of this species, as evidenced by the lack of records of antiaging activities from Cystoseira abies-marina, making this macroalga an excellent candidate for studies of its cosmeceutical potential. Ultrasound-(UAE) and microwave-assisted extraction (MAE) are advanced sustainable technologies that are very efficient in enhancing bioactive compound extraction. Applying these extraction techniques to a new biological matrix often calls for optimizing the parameters toward the best extraction yield. Since Cystoseira abies-marina is a new matrix for both UAE and MAE techniques, the present work proposes the optimization of the extraction process, using a novel approach: instead of only focusing on increasing the yield, the goal of this work is to determine the parameters for UAE and MAE that lead to extracts with better antiaging activities. For this bio-guided approach, several Cystoseira abies-marina extracts were prepared by UAE and MAE under varying conditions of solvent, time, and algae/solvent ratios. Their antiaging activities were then determined, and all the results combined to unveil the conditions yielding extracts with higher cosmeceutical potential. Using statistical tools, it was found that, for UAE, the best conditions were ethyl acetate, 15 min, and a ratio of 1:4, which led to an extract with high yield, and causing the strong inhibition of tyrosinase and elastase. In turn, ethanol, 10 min, and a ratio of 1:4 were the best conditions for MAE, leading to the extract with the best antioxidant activity. The results show that the proposed bio-guided approach was effective in obtaining extracts with high cosmeceutical potential, unveiling the possibility of modulating an extract's activity by changing the extraction method.

Aqueous and Ethanolic Plant Extracts as Bio-Insecticides-Establishing a Bridge between Raw Scientific Data and Practical Reality.

Global demand for food production is causing pressure to produce faster and bigger crop yields, leading to a rampant use of synthetical pesticides. To combat the nefarious consequences of its uses, a search for effective alternatives began in the last decades and is currently ongoing. Nature is seen as the main source of answers to crop protection problems, supported by several examples of plants/extracts used for this purpose in traditional agriculture. The literature reviewed allowed the identification of 95 plants whose extracts exhibit insecticide activity and can be used as bio-pesticides contributing to sustainable agriculture. The option for ethanol and/or water extracts is more environmentally friendly and resorts to easily accessible solvents, which can be reproduced by farmers themselves. This enables a bridge to be established between raw scientific data and a more practical reality. Azadirachta indica, Capsicum annuum, Nicotiana tabacum and Tagetes erecta are the most researched plants and have the potential to be viable options in the pest management approach. Azadirachta indica showed the most promising results and Brevicoryne brassicae was the most targeted pest species, being tested against the aqueous and/or ethanolic extracts of 23 different plants. Maceration using dried material (usually leaves) is the extraction method preferred by the majority of authors.

Secondary Metabolites in Edible Species: Looking beyond Nutritional Value.

Secondary metabolites are organic molecules of low molecular weight, biosynthesized by any living being using a wide range of biosynthetic pathways, known as secondary metabolism [...].

Phytochemicals with Added Value from Morella and Myrica Species.

Terrestrial plants, due to their sessile nature, are highly exposed to environmental pressure and therefore need to produce very effective molecules that enable them to survive all the threats. Myrica and Morella (Myricaceae) are taxonomically close genera, which include species of trees or shrubs with edible fruits that exhibit relevant uses in traditional medicine. For instance, in Chinese or Japanese folk medicine, they are used to treat diarrhea, digestive problems, headache, burns, and skin diseases. A wide array of compounds isolated from different parts of Myrica and/or Morella species possess several biological activities, like anticancer, antidiabetic, anti-obesity, and cardio-/neuro-/hepatoprotective activities, both in vitro and in vivo, with myricanol, myricitrin, quercitrin, and betulin being the most promising. There are still many other compounds isolated from both genera whose biological activities have not been evaluated, which represents an excellent opportunity to discover new applications for those compounds and valorize Morella/Myrica species.

Uncharted Source of Medicinal Products: The Case of the Hedychium Genus.

A current research topic of great interest is the study of the therapeutic properties of plants and of their bioactive secondary metabolites. Plants have been used to treat all types of health problems from allergies to cancer, in addition to their use in the perfumery industry and as food. Hedychium species are among those plants used in folk medicine in several countries and several works have been reported to verify if and how effectively these plants exert the effects reported in folk medicine, studying their essential oils, extracts and pure secondary metabolites. Hedychium coronarium and Hedychium spicatum are the most studied species. Interesting compounds have been identified like coronarin D, which possesses antibacterial, antifungal and antitumor activities, as well as isocoronarin D, linalool and villosin that exhibit better cytotoxicity towards tumor cell lines than the reference compounds used, with villosin not affecting the non-tumor cell line. Linalool and α-pinene are the most active compounds found in Hedychium essential oils, while ß-pinene is identified as the most widespread compound, being reported in 12 different Hedychium species. Since only some Hedychium species have been investigated, this review hopes to shed some light on the uncharted territory that is the Hedychium genus.

A Green and Simple Protocol for Extraction and Application of a Peroxidase-Rich Enzymatic Extract.

Recently there is a great social expectation that scientists should produce more sustainable and environmentally friendly chemical processes. Within this necessity, biocatalysis presents many attractive features because reactions are often performed in water, under mild conditions, the catalyst is biodegradable and can be obtained from renewable raw materials. In this work, we propose a simple, rapid and low-cost method for the preparation and application of an enzymatic extract from turnip root. The protocol described includes (1) the preparation of the enzymatic extract, (2) the procedure for the assessment of the more favorable working parameters (temperature, pH) and (3) the methodology for the application of the extract as the catalyst for biotransformation reactions. We anticipate that the protocol in this research will provide a simple way for obtaining an enzymatic extract which can operate efficiently under mild conditions and can effectively catalyze the biotransformation of simple phenols.

Research Advances on Health Effects of Edible Artemisia Species and Some Sesquiterpene Lactones Constituents.

The genus Artemisia, often known collectively as "wormwood", has aroused great interest in the scientific community, pharmaceutical and food industries, generating many studies on the most varied aspects of these plants. In this review, the most recent evidence on health effects of edible Artemisia species and some of its constituents are presented and discussed, based on studies published until 2020, available in the Scopus, Web of Sciences and PubMed databases, related to food applications, nutritional and sesquiterpene lactones composition, and their therapeutic effects supported by in vivo and clinical studies. The analysis of more than 300 selected articles highlights the beneficial effect on health and the high clinical relevance of several Artemisia species besides some sesquiterpene lactones constituents and their derivatives. From an integrated perspective, as it includes therapeutic and nutritional properties, without ignoring some adverse effects described in the literature, this review shows the great potential of Artemisia plants and some of their constituents as dietary supplements, functional foods and as the source of new, more efficient, and safe medicines. Despite all the benefits demonstrated, some gaps need to be filled, mainly related to the use of raw Artemisia extracts, such as its standardization and clinical trials on adverse effects and its health care efficacy.

Seaweed Secondary Metabolites with Beneficial Health Effects: An Overview of Successes in In Vivo Studies and Clinical Trials.

Macroalgae are increasingly viewed as a source of secondary metabolites with great potential for the development of new drugs. In this development, in vitro studies are only the first step in a long process, while in vivo studies and clinical trials are the most revealing stages of the true potential and limitations that a given metabolite may have as a new drug. This literature review aims to give a critical overview of the secondary metabolites that reveal the most interesting results in these two steps. Phlorotannins show great pharmaceutical potential in in vivo models and, among the several examples, the anti-dyslipidemia activity of dieckol must be highlighted because it was more effective than lovastatin in an in vivo model. The IRLIIVLMPILMA tridecapeptide that exhibits an in vivo level of activity similar to the hypotensive clinical drug captopril should still be stressed, as well as griffithsin which showed such stunning results over a variety of animal models and which will probably move onto clinical trials soon. Regarding clinical trials, studies with pure algal metabolites are scarce, limited to those carried out with kahalalide F and fucoxanthin. The majority of clinical trials currently aim to ascertain the effect of algae consumption, as extracts or fractions, on obesity and diabetes.

Current Trends on Seaweeds: Looking at Chemical Composition, Phytopharmacology, and Cosmetic Applications.

Seaweeds have received huge interest in recent years given their promising potentialities. Their antioxidant, anti-inflammatory, antitumor, hypolipemic, and anticoagulant effects are among the most renowned and studied bioactivities so far, and these effects have been increasingly associated with their content and richness in both primary and secondary metabolites. Although primary metabolites have a pivotal importance such as their content in polysaccharides (fucoidans, agars, carragenans, ulvans, alginates, and laminarin), recent data have shown that the content in some secondary metabolites largely determines the effective bioactive potential of seaweeds. Among these secondary metabolites, phenolic compounds feature prominently. The present review provides the most remarkable insights into seaweed research, specifically addressing its chemical composition, phytopharmacology, and cosmetic applications.

Ethnobotanical Knowledge in Sete Cidades, Azores Archipelago: First Ethnomedicinal Report.

Knowledge about folk medicines is limited to elder community members of remote communities, like Sete Cidades in the Azores. The Azores, 1300 km west of Portugal, are nine volcanic islands, totalling 2330 km2 of land dispersed by 173,200 km2 in the North Atlantic Ocean. The present study aims to scientifically document the uses of plant species for medicinal purposes, in the Sete Cidades. Twenty-eight community members from 40 to 84 years of age, of whom half were 55 to 64 years old, were interviewed. Twenty-nine taxa were reported as being used for medicinal purposes, ten of which have not been previously reported for ethnomedicinal use in Portugal, with a first record of the use of Morella faya. Leaves were the most used plant part (55%), and decoction the most common preparation mode. The five reported taxa with both the highest use value (0.71-0.25) and relative frequency of citation (0.14-0.11) were Clinopodium menthifolium subsp. ascendens, Aloysia citriodora, Mentha x piperita, Citrus limon and Rosmarinus officinalis. The traditional uses of some of the reported plants are supported by scientific studies, confirming their ethnomedicinal value and the need to preserve local knowledge of folk medicine practices.

Euphorbia-Derived Natural Products with Potential for Use in Health Maintenance.

Euphorbia genus (Euphorbiaceae family), which is the third largest genus of angiosperm plants comprising ca. 2000 recognized species, is used all over the world in traditional medicine, especially in the traditional Chinese medicine. Members of this taxa are promptly recognizable by their specialized inflorescences and latex. In this review, an overview of Euphorbia-derived natural products such as essential oils, extracts, and pure compounds, active in a broad range of biological activities, and with potential usages in health maintenance, is described. The chemical composition of essential oils from Euphorbia species revealed the presence of more than 80 phytochemicals, mainly oxygenated sesquiterpenes and sesquiterpenes hydrocarbons, while Euphorbia extracts contain secondary metabolites such as sesquiterpenes, diterpenes, sterols, flavonoids, and other polyphenols. The extracts and secondary metabolites from Euphorbia plants may act as active principles of medicines for the treatment of many human ailments, mainly inflammation, cancer, and microbial infections. Besides, Euphorbia-derived products have great potential as a source of bioactive extracts and pure compounds, which can be used to promote longevity with more health.

Biological Potential and Medical Use of Secondary Metabolites.

This Medicines special issue focuses on the great potential of secondary metabolites for therapeutic applications. The special issue contains 16 articles reporting relevant experimental results and overviews of bioactive secondary metabolites. Their biological effects and new methodologies that improve the lead compounds' synthesis were also discussed. We would like to thank all 83 authors, from all over the world, for their valuable contributions to this special issue.

Inula L. Secondary Metabolites against Oxidative Stress-Related Human Diseases.

An imbalance in the production of reactive oxygen species in the body can cause an increase of oxidative stress that leads to oxidative damage to cells and tissues, which culminates in the development or aggravation of some chronic diseases, such as inflammation, diabetes mellitus, cancer, cardiovascular disease, and obesity. Secondary metabolites from Inula species can play an important role in the prevention and treatment of the oxidative stress-related diseases mentioned above. The databases Scopus, PubMed, and Web of Science and the combining terms Inula, antioxidant and secondary metabolites were used in the research for this review. More than 120 articles are reviewed, highlighting the most active compounds with special emphasis on the elucidation of their antioxidative-stress mechanism of action, which increases the knowledge about their potential in the fight against inflammation, cancer, neurodegeneration, and diabetes. Alantolactone is the most polyvalent compound, reporting interesting EC50 values for several bioactivities, while 1-O-acetylbritannilactone can be pointed out as a promising lead compound for the development of analogues with interesting properties. The Inula genus is a good bet as source of structurally diverse compounds with antioxidant activity that can act via different mechanisms to fight several oxidative stress-related human diseases, being useful for development of new drugs.

Seaweed Secondary Metabolites In Vitro and In Vivo Anticancer Activity.

Isolation, finding or discovery of novel anticancer agents is very important for cancer treatment, and seaweeds are one of the largest producers of chemically active metabolites with valuable cytotoxic properties, and therefore can be used as new chemotherapeutic agents or source of inspiration to develop new ones. Identification of the more potent and selective anticancer components isolated from brown, green and red seaweeds, as well as studies of their mode of action is very attractive and constitute a small but relevant progress for pharmacological applications. Several researchers have carried out in vitro and in vivo studies in various cell lines and have disclosed the active metabolites among the terpenoids, including carotenoids, polyphenols and alkaloids that can be found in seaweeds. In this review the type of metabolites and their cytotoxic or antiproliferative effects will be discussed additionally their mode of action, structure-activity relationship and selectivity will also be revealed. The diterpene dictyolactone, the sterol cholest-5-en-3ß,7α-diol and the halogenated monoterpene halomon are among the reported compounds, the ones that present sub-micromolar cytotoxicity. Additionally, one dimeric sesquiterpene of the cyclolaurane-type, three bromophenols and one halogenated monoterpene should be emphasized because they exhibit half maximal inhibitory concentration (IC50) values between 1⁻5 µM against several cell lines.

The Current Status of the Pharmaceutical Potential of Juniperus L. Metabolites.

Background: Plants and their derived natural compounds possess various biological and therapeutic properties, which turns them into an increasing topic of interest and research. Juniperus genus is diverse in species, with several traditional medicines reported, and rich in natural compounds with potential for development of new drugs. Methods: The research for this review were based in the Scopus and Web of Science databases using terms combining Juniperus, secondary metabolites names, and biological activities. This is not an exhaustive review of Juniperus compounds with biological activities, but rather a critical selection taking into account the following criteria: (i) studies involving the most recent methodologies for quantitative evaluation of biological activities; and (ii) the compounds with the highest number of studies published in the last four years. Results: From Juniperus species, several diterpenes, flavonoids, and one lignan were emphasized taking into account their level of activity against several targets. Antitumor activity is by far the most studied, being followed by antibacterial and antiviral activities. Deoxypodophyllotoxin and one dehydroabietic acid derivative appears to be the most promising lead compounds. Conclusions: This review demonstrates the Juniperus species value as a source of secondary metabolites with relevant pharmaceutical potential.

Overview on the Antihypertensive and Anti-Obesity Effects of Secondary Metabolites from Seaweeds.

Hypertension and obesity are two significant factors that contribute to the onset and exacerbation of a cascade of mechanisms including activation of the sympathetic and renin-angiotensin systems, oxidative stress, release of inflammatory mediators, increase of adipogenesis and thus promotion of systemic dysfunction that leads to clinical manifestations of cardiovascular diseases. Seaweeds, in addition to their use as food, are now unanimously acknowledged as an invaluable source of new natural products that may hold noteworthy leads for future drug discovery and development, including in the prevention and/or treatment of the cardiovascular risk factors. Several compounds including peptides, phlorotannins, polysaccharides, carotenoids, and sterols, isolated from brown, red and green macroalgae exhibit significant anti-hypertensive and anti-obesity properties. This review will provide a comprehensive overview of the recent advances on bioactive pure compounds isolated from different seaweed sources focusing on their potential use as drugs to treat or prevent hypertension and obesity. On the other hand, although it is obvious that macroalgae represent promising sources of antihypertensive and anti-obesity compounds, it is also clear that further efforts are required to fully understand their cellular mechanisms of action, to establish structure-inhibition relationships and mainly to evaluate them in pre-clinical and clinical trials.

Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application.

Cancer is a multistage process resulting in an uncontrolled and abrupt division of cells and is one of the leading causes of mortality. The cases reported and the predictions for the near future are unthinkable. Food and Drug Administration data showed that 40% of the approved molecules are natural compounds or inspired by them, from which, 74% are used in anticancer therapy. In fact, natural products are viewed as more biologically friendly, that is less toxic to normal cells. In this review, the most recent and successful cases of secondary metabolites, including alkaloid, diterpene, triterpene and polyphenolic type compounds, with great anticancer potential are discussed. Focusing on the ones that are in clinical trial development or already used in anticancer therapy, therefore successful cases such as paclitaxel and homoharringtonine (in clinical use), curcumin and ingenol mebutate (in clinical trials) will be addressed. Each compound's natural source, the most important steps in their discovery, their therapeutic targets, as well as the main structural modifications that can improve anticancer properties will be discussed in order to show the role of plants as a source of effective and safe anticancer drugs.

Targeting human pathogenic bacteria by siderophores: A proteomics review.

UNLABELLED: Human bacterial infections are still a major public health problem throughout the world. Therefore it is fundamental to understand how pathogenic bacteria interact with their human host and to develop more advanced drugs or vaccines in response to the increasing bacterial resistance. Since iron is essential to bacterial survival and growth inside the host tissues, these microorganisms have developed highly efficient iron-acquisition systems; the most common one involves the secretion of iron chelators into the extracellular environment, known as siderophores, and the corresponding siderophore-membrane receptors or transporters responsible for the iron uptake. In the past few decades, several biochemical methods and genetic screens have been employed to track down and identify these iron-scavenging molecules. However, compared with the previous "static" approaches, proteomic identification is revealing far more molecules through full protein mapping and becoming more rapid and selective, leading the scientific and medical community to consider standardizing proteomic tools for clinical biomarker detection of bacterial infectious diseases. In this review, we focus on human pathogenic Gram-negative bacteria and discuss the importance of siderophores in their virulence and the available proteomic strategies to identify siderophore-related proteins and their expression level under different growth conditions. The promising use of siderophore antibiotics to overcome bacterial resistance and the future of proteomics in the routine clinical care are also mentioned. SIGNIFICANCE: Proteomic strategies to identify siderophore-related proteins and their expression level can be helpful to control and/or find a cure of infectious deseases especially if related with multidrug resistance. Siderophores are low-molecular-weight compounds produced by bacteria which can become clinical biomarkers and/or antibiotics used mainly in "Trojan horse" type strategies. Due to the above mention we think that the promising use of siderophore to overcome bacterial resistance and the future of proteomics in the routine clinical care is a hot topic that should be discussed.