Marine Extracts Research Articles

Natural products for male androgenetic alopecia.

Androgenetic alopecia (AGA) is the most common cause of hair loss in men, often requiring medical attention. The US FDA approved topical minoxidil and oral finasteride to treat AGA. Topical minoxidil requires a long-term application to observe improvement; oral finasteride may cause undesirable side effects. Therefore, natural products may be an alternative when patients are skeptical about these two conventional treatments. Physicians may also suggest natural products in conjunction with topical minoxidil or oral finasteride to enhance clinical outcomes. This article reviews the prospect of natural products in treating male AGA. A systematic search was conducted in PubMed, CINAHL, Scopus, Web of Science, and EMBASE (Ovid) on July 19, 2021. In addition, the bibliographies of selected articles were hand-searched to identify relevant studies. After deduplication and screening, 11 clinical studies meet the criteria for detailed review. The selected clinical studies suggest that saw palmetto, caffeine, melatonin, marine extracts, rosemary oil, procyanidin, pumpkin seed oil, and cannabidiol oil might be considered in male AGA treatment.

AntiGan: An Epinutraceutical Bioproduct with Antitumor Properties in Cultured Cell Lines.

Novel and effective chemotherapeutic agents are needed to improve cancer treatment. Epidrugs are currently used for cancer therapy but also exhibit toxicity. Targeting the epigenetic apparatus with bioproducts may aid cancer prevention and treatment. To determine whether the lipoprotein marine extract AntiGan shows epigenetic and antitumor effects, cultured HepG2 (hepatocellular carcinoma) and HCT116 (colorectal carcinoma) cell lines were treated with AntiGan (10, 50, 100, and to 500 µg/mL) for 24 h, 48 h, and 72 h. AntiGan (10 µg/mL) reduced cell viability after 48 h and increased Bax expression; AntiGan (10 and 50 µg/mL) increased caspase-3 immunoreactivity in HepG2 and HCT116 cells. AntiGan (10 and 50 µg/mL) attenuated COX-2 and IL-17 expression in both cell lines. AntiGan (10 µg/mL) increased 5mC levels in both cell types and reduced DNMT1 and DNMT3a expression in these cells. AntiGan (10 and 50 µg/mL) promoted DNMT3a immunoreactivity and reduced SIRT1 mRNA expression in both cell types. In HCT116 cells treated with AntiGan (10 µg/mL), SIRT1 immunoreactivity localized to nuclei and the cytoplasm; AntiGan (50 µg/mL) increased cytoplasmic SIRT1 localization in HCT116 cells. AntiGan is a novel antitumoral bioproduct with epigenetic properties (epinutraceutical) for treating liver and colorectal cancer.

Dysidenin from the Marine Sponge Citronia sp. Affects the Motility and Morphology of Haemonchus contortus Larvae In Vitro.

High-throughput screening of the NatureBank marine extract library (n = 7616) using a phenotypic assay for the parasitic nematode Haemonchus contortus identified an active extract derived from the Australian marine sponge Citronia sp. Bioassay-guided fractionation of the CH2Cl2/MeOH extract from Citronia sp. resulted in the purification of two known hexachlorinated peptides, dysidenin (1) and dysideathiazole (2). Compound 1 inhibited the growth/development of H. contortus larvae and induced multiple phenotypic changes, including a lethal evisceration (Evi) phenotype and/or somatic cell and tissue destruction. This is the first report of anthelmintic activity for these rare and unique polychlorinated peptides.

Response of Gazania Plants (Gazania Splendens L.) to Seaweed Extract (Tecamin Algae) and Nano Stimulator (Proteck CalBor)

The study was conducted in the lath house of the Department of the Horticulture and Landscape - College of Agriculture during the growing season of 2020-2021 inGazania plants, in order to study the effect of ground addition of marine algae extract (Tecamin Algae) at concentrations (0, 2 and 4 ml L-1), symbolized by (A0, A1 and A2) respectively, and spraying with the nanostimulator (Proteck CalBor) manufactured according to nanotechnology in concentrations (0, 0.5 and 1 ml L-1) and it has a symbol (B0, B1 and B2). The results showed that the treatments of adding the extract (Tecamin Algae), especially at concentration A2 (4 ml L-1) contributed to achieving the best results for all vegetative and flowering growth traits (plant height, number of leaves, vegetative dry weight, number of offsprings, leaf content of chlorophyll, total carbohydrates content of leaves, number of flowers, flower fresh weight, flower diameter, flower peduncle length), they were (13.65 cm, 34.64 leaf plant-1, 6.38 g, 7.72 offspring plant-1, 10.94 mg g-1, 7.44%, 5.56 flower plant-1, 2.26 g, 6.08 cm and 9.75 cm), respectively. A Spraying with nano stimulator (Proteck CalBor) achieved significant effect, especially B2 (1 ml L-1) concentration, that gave the highest values for the traits (plant height, vegetative dry weight, number of off springs, leaf content of chlorophyll, total carbohydrates content of leaves, number of flowers, flower fresh weight and flower diameter), they were (13.38 cm, 6.47 g, 7.48 offspring plant-1, 10.61 mg g-1, 7.49%, 5.40 flower plant-1, 2.41 g and 6.40 cm), respectively.

Functional Feeds to Tackle Meagre (Argyrosomus regius) Stress: Physiological Responses under Acute Stressful Handling Conditions.

Marine algae are recognised sources of bioactive compounds that have attracted great interest as nutritional supplements for aquaculture fish. Intensive rearing conditions often expose fish to husbandry-related stressors, rendering fish more susceptible to disease and reducing production yields. The present work evaluated the potential of two marine algae extracts (Fucus vesiculosus and Nannochloropsis gaditana) as nutritional supplements to mitigate stress effects in meagre (Argyrosomus regius) exposed to an acute handling stress (AS). A plant-based diet was used as a control, and three other diets were prepared, which were similar to the control diet but supplemented with 1% of each algal extract or a combination of the two extracts (0.5% each). The effects of supplemented diets on stress biomarkers, antioxidant enzyme activities, and immune response were analysed in fish exposed to AS after 4 weeks of feeding. Supplemented diets did not affect growth performance but the inclusion of F. vesiculosus promoted higher feed efficiency, as compared to the control group. Dietary algal extracts supplementation reduced plasma glucose levels, increased white blood cell counts, and reduced the expression of pro-inflammatory genes when compared with the control. N. gaditana supplementation led to a reduction in hepatic antioxidant enzyme activity and glutathione levels, while F. vesiculosus supplementation increased muscle glutathione reductase activity and reduced lipid peroxidation. These findings support the potential of algal extracts as nutraceuticals in aquafeeds to enhance the ability of fish to cope with husbandry-related stressful conditions and ultimately improve fish health and welfare.

Study on bio-fish extract and cultivation dates to improve production of flax (Linum usitatissimum) in Omar-Mukhtar area, Libya

Flax seeds (Linum usitatissimum L.) are known to be very useful source of fiber and nutrition soil; also boi-fish extract has shown to be a from of organic fertilizer of very high quality. Our objective is to contribute to the research effort to produce healthy, safe and organic crops, while saving the soil from being damaged and the environment for any harmful materials. Therefore, we conducted study in Omar-Mukhtar Al-Jabal Al-Akhdar district in northeastern Libya, in the growing seasons of 2016–17 and 2017–18 in to examine the effect of marine bio-fish extract as organic fertilization and of different cultivation dates on improving yields for three flax varieties cultivated. The experiment was laid under split-split plot design utilizing three-factor complete randomized block design organized with three replicates. Bio-fish extract was added to the main plots at a rate of 5 L/ha and control, sub-plots to three flax varieties (Giza11, L.22 and Sakha4) sub-sub plots, on two cultivation dates of 11 October and 11 November. Agronomic Efficiency (AE) of the flax crop with adding the bio-fish extract for L.22 was 0.034 and 0.018 t grain ha/L for seasons 2016/17 and 2017/18, respectively. The higher grain yield was 1.50 t/ha for season 2016/17 and 0.53 t/ha for season 2017/18, when adding the fish extract for strain L.22 and cultivation date of 11 October. Thus, adding the fish extract led to an increase in grain yield, oil, and fiber content. With the bio-fish fertilization, strain L.22 was better in oil. Also, sowing on November 11 with the addition of fish extract resulted in a higher fiber proportion in the yielded crop.

Marine algae as emerging therapeutic alternatives for depression: A review.

Depression is a complex heterogeneous brain disorder characterized by a range of symptoms, resulting in psychomotor and cognitive disabilities and suicidal thoughts. Its prevalence has reached an alarming level affecting millions of people globally. Despite advances in current pharmacological treatments, the heterogenicity of clinical response and incidences of adverse effects have shifted research focus to identification of new natural substances with minimal or no adverse effects as therapeutic alternatives. Marine algae-derived extracts and their constituents are considered potential sources of secondary metabolites with diverse beneficial effects. Marine algae with enormous health benefits are emerging as a natural source for discovering new alternative antidepressants. Its medicinal properties exhibited shielding efficacy against neuroinflammation, oxidative stress, and mitochondrial dysfunction, which are indicated to underlie the pathogenesis of many neurological disorders. Marine algae have been found to ameliorate depressive-like symptoms and behaviors in preclinical and clinical studies by restoring monoaminergic neurotransmission, hypothalamic-pituitary-adrenal axis function, neuroplasticity, and continuous neurogenesis in the dentate gyrus of the hippocampus via modulating brain-derived neurotrophic factors and antineuroinflammatory activity. Although antidepressant effects of marine algae have not been validated in comparison with currently available synthetic antidepressants, they have been reported to have effects on the pathophysiology of depression, thus suggesting their potential as novel antidepressants. In this review, we analyzed the currently available research on the potential benefits of marine algae on depression, including their effects on the pathophysiology of depression, potential clinical relevance of their antidepressant effects in preclinical and clinical studies, and the underlying mechanisms of these effects.

Synthetic Iowaite Can Effectively Remove Inorganic Arsenic from Marine Extract.

For the removal of arsenic from marine products, iowaite was prepared and investigated to determine the optimal adsorption process of arsenic. Different chemical forms of arsenic (As(III), As(V)) with varying concentrations (0.15, 1.5, 5, 10, 15, and 20 mg/L) under various conditions including pH (3, 5, 7, 9, 11) and contact time (1, 2, 5, 10, 15, 30, 60, 120, 180 min) were exposed to iowaite. Adsorption isotherms and metal ions kinetic modeling onto the adsorbent were determined based on Langmuir, Freundlich, first- and second-order kinetic models. The adsorption onto iowaite varied depending on the conditions. The adsorption rates of standard solution, As(III) and As(V) exceeded 95% under proper conditions, while high complexity was noted with marine samples. As(III) and As(V) from Mactra veneriformis extraction all decreased when exposed to iowaite. The inclusion morphology and interconversion of organic arsenic limit adsorption. Iowaite can be efficiently used for inorganic arsenic removal from wastewater and different marine food products, which maybe other adsorbent or further performance of iowaite needs to be investigated for organic arsenic.

Marine Animal-Derived Compounds and Autophagy Modulation in Breast Cancer Cells

It is known that in breast cancer biology, autophagy mainly plays a cytoprotective and anti-apoptotic role in vitro, being conceivably responsible for cell resistance to drug exposure and a higher metastatic attitude in vivo. Thus, the development of novel autophagy-targeting agents represents a valuable strategy to improve the efficacy of anticancer interventions. It is widely acknowledged that the enormous biodiversity of marine organisms represents a highly promising reserve for the isolation of bioactive primary and secondary metabolites targeting one or several specific molecular pathways and displaying active pharmacological properties against a variety of diseases. The aim of this review is to pick up selected studies that report the extraction and identification of marine animal-derived extracts or isolated compounds which exert a modulatory effect on the autophagic process in breast cancer cells and list them with respect to the taxonomical hierarchy of the producing species. Where available, the molecular and biochemical aspects associated with the molecules or extracts under discussion will be also summarized.

Anticoagulant Activity of Sulfated Polysaccharides and Polyphenols Extracted from Marine Algae

Background: Recent studies have provided evidence that marine algae sulfated polysaccharides and phlorotannins play an important role in human health. The aim of this study was to evaluate the anticoagulant activity of five marine algae extracts from Bejaia’s coast (Algeria). Methods: Phenolic and sugar contents of the five marine algae were assessed using folin ciocalteu and anthrone reagents, respectively. The anticoagulant activity was evaluated by the Activated Partial Thromboplastin Time (APTT) and Prothrombin Time (PT). Results: Higher contents of phenolic compounds were obtained with ethanol for Cystoseira humilis, Halopteris scoparia, Padina pavonica, and Rhodomela confervoides (8.55±0.29, 7.84±0.47, 6.41±0.14 and 4.16±0.04 mg CE/g of dw, respectively). Whereas, for Sargassum vulgare, the extraction with acetone showed higher content (3.04±0.071 mg CE/g of dw). The determination of sugar content showed that acetone extract of the five seaweeds was the richest in sugar, this rate increasingly dropped in ethanol extract and the fractions A and B. The red algae Rhodomela confervoides showed a significant anticoagulant activity in ethanol extract and the fractions A, B, and C, with elongation up to 407.97±58.12 s in the fraction C, at a concentration of 10 mg/mL. Anticoagulant activity was observed in the fractions A, B, and C of all the brown seaweeds. Procoagulant activity was observed in the fractions A and B of Cystoseira humilis and Sargassum vulgare, as well as the fraction B of Padina pavonica for an indeterminate period, at 10 mg/mL. Conclusion: The sulfated polysaccharides present in the fractions A, B and C of the studied marine algae may be responsible for the anticoagulant activity. So, they can be developed as a novel anticoagulant in the pharmaceutical industry.

Effect of liquid seaweed extracts as biostimulant on vegetative growth of soybean

Seaweeds are an important sustainable marine source and extracts from them have been applied as plant biostimulants. Seaweed-based extracts have been recently employed as sustainable tools to improve abiotic stress tolerance and increase growth and quality of plant. The research aimed to evaluate the effect of liquid seaweed extracts from some species of seaweeds with different concentrations on vegetative growth of soybean. Samples of seaweed were collected on Kasiak Gadang Island, Nirwana Beach, Padang, West Sumatra. Species of seaweed we tested were Padina minor, Sargassum crassifolium, Sargassum cristaefolium and Turbinaria decurrens and concentration of liquid extracts were control, 0.1%, 0.2%, 0.3%, and 0.4%. The result showed that P. minor liquid extract increasing some parameters including height, number of leaves, number of branches and fresh weight. While the dry weight of soybean was similar among the treatments in soybean. 0.4% concentration of seaweed extract significantly improves all parameters of vegetative growth of soybean.

A Nudibranch Marine Extract Selectively Chemosensitizes Colorectal Cancer Cells by Inducing ROS-Mediated Endoplasmic Reticulum Stress.

The present study shows the putative antiproliferative mechanism of action of the previously analytically characterized nudibranch extract (Dolabella auricularia, NB) and its different effects in colon cancer cells vs. nontumor colon cells. NB extract increased the accumulation of reactive oxygen species (ROS) and increased endoplasmic reticulum (ER) stress via stimulation of the unfolded protein response. Stress scavengers, N-acetylcysteine (NAC) and 4-phenylbutyric acid (4-PBA), decreased the stress induced by NB. The results showed that NB extract increased ER stress through overproduction of ROS in superinvasive colon cancer cells, decreased their resistance threshold, and produced a nonreturn level of ER stress, causing DNA damage and cell cycle arrest, which prevented them from achieving hyperproliferative capacity and migrating to and invading other tissues. On the contrary, NB extract had a considerably lower effect on nontumor human colon cells, suggesting a selective effect related to stress balance homeostasis. In conclusion, our results confirm that the growth and malignancy of colon cancer cells can be decreased by marine compounds through the modification of one of the most potent resistance mechanisms present in tumor cells; this characteristic differentiates cancer cells from nontumor cells in terms of stress balance.

Bioactivity of two marine algae extracts and their synthesized silver nanoparticles as safe controls against Musca domestica housefly

AbstractIn this study, two marine algae, Avrainvillea amadelpha and Codium edule, and their synthesized silver nanoparticles were evaluated against the second larval instars of the housefly Musca domestica. The marine algae‐fabricated silver nanoparticles (AgNPs) were examined by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X‐ray diffraction analysis (XRD). The precolored aqueous silver solution changed from pale yellow to brown by mixing the algae extracts, revealing Ag nanocomposite production. There was a maximum UV–vis absorption at 400 nm for A. amadelpha and 420 nm for C. edule. SEM results showed that the A. amadelpha‐ and C. edule‐fabricated AgNPs were spherical and irregular in shape. A. amadelpha extract alone gave higher effective mortalities against M. domestica larvae, which were 22.1–98.3% in the tested concentrations (62.5–1,000 ppm), while a highly significant increased mortality (36.9–99.7%) was obtained from concentrations ranging from 6.3–100 ppm when A. amadelpha extract was mixed with silver nanoparticles. C. edule extract alone gave moderate effective control with 15.9–90.3% mortality using the above concentrations, whereas the mortality significantly increased (21.8–95.8%) with concentrations ranging from 6.3–100 ppm when C. edule extract was mixed with silver nanoparticles. According to the LC50 values, A. amadelpha with silver nanoparticles (LC50 9.66 ppm) provided more effective control against larval stages of M. domestica than A. amadelpha alone (LC50 133.08 ppm) by a factor of 13.776. Additionally, C. edule alone provided moderately effective control (LC50 300.37 ppm), while when mixed with silver nanoparticles, it provided highly effective control (LC50 21.34 ppm) by a factor of 14.075. Some algae extracts that synthesize silver nanoparticles offer a promising role in housefly integrated pest management (IPM) and may be an effective alternative to conventional synthetic insecticides.

Identification of Bioactive Compounds from Marine Natural Products and Exploration of Structure-Activity Relationships (SAR).

Marine natural products (MNPs) have been an important and rich source for antimicrobial drug discovery and an effective alternative to control drug resistant infections. Herein, we report bioassay guided fractionation of marine extracts from sponges Lendenfeldia, Ircinia and Dysidea that led us to identify novel compounds with antimicrobial properties. Tertiary amines or quaternary amine salts: aniline 1, benzylamine 2, tertiary amine 3 and 4, and quaternary amine salt 5, along with three known compounds (6–8) were isolated from a crude extract and MeOH eluent marine extracts. The antibiotic activities of the compounds, and their isolation as natural products have not been reported before. Using tandem mass spectrometry (MS) analysis, potential structures of the bioactive fractions were assigned, leading to the hit validation of potential compounds through synthesis, and commercially available compounds. This method is a novel strategy to overcome insufficient quantities of pure material (NPs) for drug discovery and development which is a big challenge for pharmaceutical companies. The antibacterial screening of the marine extracts has shown several of the compounds exhibited potent in-vitro antibacterial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) values between 15.6 to 62.5 microg mL−1. Herein, we also report structure activity relationships of a diverse range of commercial structurally similar compounds. The structure-activity relationships (SAR) results demonstrate that modification of the amines through linear chain length, and inclusion of aromatic rings, modifies the observed antimicrobial activity. Several commercially available compounds, which are structurally related to the discovered molecules, showed broad-spectrum antimicrobial activity against different test pathogens with a MIC range of 50 to 0.01 µM. The results of cross-referencing antimicrobial activity and cytotoxicity establish that these compounds are promising potential molecules, with a favourable therapeutic index for antimicrobial drug development. Additionally, the SAR studies show that simplified analogues of the isolated compounds have increased bioactivity.

The potential impact of Octopus cyanea extracts to improve eggplant resistance against Fusarium-wilt disease: in vivo and in vitro studies.

The novelty of the present research is conducting a new method in the systemic resistance of plant diseases by using distinct marine extracts. The ability of two octopus extracts to reduce the wilt disease caused by Fusarium oxysporum was observed. The applied methods are soaked roots (SR) and foliar shoots (FS). The antioxidant enzyme activities, percent disease index (PDI), and growth parameters were measured. In vitro antifungal potential of the octopus extracts against F. oxysporum was examined. The obtained result shows that SR extracts reduced PDI. Additionally, all the tested treatments promoted the growth and photosynthetic pigments of the infected plants. SR (in ethanolic extracts) was the most prominent inducer which offered a high advancement in the total soluble protein contents. Also, SR (in methanolic extracts) was the most suitable inducer which provided a very necessary development not only in the total phenol but also in the peroxidase (POD) and polyphenol oxidase (PPO) activities. GC-MS investigation of the octopus extracts exhibited that the compounds which possess antifungal activity were furoscrobiculin B and/or eugenol. They demonstrated a notable antifungal potential against F. oxysporum with a maximum activity of 38.5 and 12.7 mm ZOI after the treatment with the ethanolic and methanolic extract, respectively. FTIR results illustrated the functional group of the compound responsible for the antifungal activity. Additionally, an atomic absorption result reveals that there are traces of metals detected such as Pb, Ag, Cu, Zn, and Mg. The antifungal activity was decreased as the concentrations were reduced. Accordingly, the present extracts may be used as the vital agents in the agricultural field to restrain the plant pathogenic fungi, especially F. oxysporum from a proliferation.

Performance of Algae Extracts Priming for Enhancing Seed Germination Indices and Salt Tolerance in Calotropis procera (Aiton) W.T

Salt stress is considered as the most critical environmental factor which negatively affects the germination, growth and establishment of trees and shrubs. Marine algae extract represents an important option of biostimulants which can improve the crop tolerance to abiotic stresses, such as salinity. In the present study, we investigated the potential of seaweed and microalga extracts as biostimulants priming agent to attenuate the effect of salt stress on seed germination and growth indices of milkweed (Calotropis procera Ait), which was grown under different salinity concentrations. Milkweed seeds were primed by the seaweed extract (SWE) of Sargassum angustifolium, and microalga extract (MAE) of Spirulina platensis at various concentrations (0, 5, 10 and 15 ml l−1) and then exposed to salt stress at four levels (0, 7.5, 15 and 30 dS m−1 of diluted seawater) in factorial experiment and completely randomized design. The results indicated that seeds primed by biostimulant germinate and also tolerate salinity up to 15 dS m−1. Although SWEs (10 ml l−1) increased germination percentage by 42% in seeds exposed to 7.5 dS m−1, the parameter was significantly enhanced using MAEs (5 ml l−1) by 60, 65 and 60% at 7.5–30 dS m−1, respectively. Also, SWE (< 10 ml l−1) improved seed vigor index by 55% and 86.6% as exposed to 0, 7.5 dS m−1, whereas MAE (5 ml l−1) increased it by 54%, 66% and 9% at 0, 7.5 and 15dS m−1, respectively. Moreover, root and shoot length as well as root–shoot ratio was markedly increased using 10 ml of both algae under salinity lower 15dS m−1 than control. SWEs and MAEs enhanced shoot weight by 30.74% and 41.6% in salinity-free control group, respectively. Both priming (< 10 ml) resulted in the raising of root dry weight in stressed-plants versus the control. The highest salt tolerance index in stressed-milkweed was found 85% at 15 dS m−1 while algae priming (< 10 ml l−1) raised it by 118% at the same salinity than control. Totally, this study demonstrates the potential of algae priming (at lower concentrations) for increasing milkweed tolerance to salinity stress and highlights the possibility of using it as biostimulant under harsh environmental conditions.

Comparison of visual detection of melamine by AuNPs sol prepared in marine and terrestrial plant extracts

We first time compared the synthesis mechanism of gold nanoparticles (AuNPs) in the marine plant extract (MPE) such as sargassum carpophyllum and spirulina and the terrestrial plant extract (TPE) as for rose petal and longan leaf. Also, the different aggregation behaviors and the color changes of AuNPs in MPE and TPE when they met melamine (Mel) were discussed. In the visual color detection of Mel, the color of AuNPs in MPE rapidly turned blue-gray from wine red encountered Mel, but it was still wine red in the TPE. The size and surface composition of AuNPs in MPE and TPE were analyzed by UV–vis, TEM, FTIR, and XPS. Meanwhile, we further clarified the reason why the AuNPs in TPE can’t colorimetric detection of Mel, despite a lot of hydroxyl groups in biomolecules.

Advances in the discovery and development of anthelmintics by harnessing natural product scaffolds.

Widespread resistance to currently-used anthelmintics represents a major obstacle to controlling parasitic nematodes of livestock animals. Given the reliance on anthelmintics in many control regimens, there is a need for the continued discovery and development of new nematocides. Enabling such a focus are: (i) the major chemical diversity of natural products; (ii) the availability of curated, drug-like extract-, fraction- and/or compound-libraries from natural sources; (iii) the utility and practicality of well-established whole-worm bioassays for Haemonchus contortus-an important parasitic nematodes of livestock-to screen natural product libraries; and (iv) the availability of advanced chromatographic (HPLC), spectroscopic (NMR) and spectrometric (MS) techniques for bioassay-guided fractionation and structural elucidation. This context provides a sound basis for the identification and characterisation of anthelmintic candidates from natural sources. This chapter provides a background on the importance and impact of helminth infections/diseases, parasite control and aspects of drug discovery, and reviews recent work focused on (i) screening well-defined compound libraries to establish the methods needed for large-scale screening of natural extract libraries; (ii) discovering plant and marine extracts with nematocidal or nematostatic activity, and purifying bioactive compounds and assessing their potential for further development; and (iii) synthesising analogues of selected purified natural compounds for the identification of possible 'lead' candidates. The chapter describes some lessons learned from this work and proposes future areas of focus for drug discovery. Collectively, the findings from this recent work show potential for selected natural product scaffolds as candidates for future development. Developing such candidates via future chemical optimisation, efficacy and safety evaluations, broad spectrum activity assessments, and target identification represents an exciting prospect and, if successful, could pave the way to subsequent pre-clinical and clinical evaluations.

Profiling the activity of edible European macroalgae towards pharmacological targets for type 2 diabetes mellitus

ABSTRACT In traditional medicine marine extracts are extensively used as therapies for diabetes. With the increasing rate of incidence of type 2 diabetes mellitus and rising cost of treatments, we investigated the anti-diabetic properties of extracts of common edible seaweeds in Europe including their ability to inhibit alpha-glucosidase and dipeptidyl peptidase 4 (DPP-4) enzymatic activity, block sodium glucose transporter-2 (SGLT-2) activity and stimulate glucagon-like peptide-1 (GLP-1) secretion and synthesis. The most promising seaweed extracts were tested for anti-hyperglycaemic activity in vivo. Some brown seaweed (Phaeophyceae) extracts had inhibitory effects on alpha-glucosidase ranging from 13.9 ± 0.2% to 89.5 ± 0.4% (p < 0.001). However, none of the seaweed extracts was able to block SGLT-2 activity. Ethanol extracts of the kelp Alaria esculenta and water extracts of Laminaria digitata strongly inhibited DPP-4 activity by 91.3 ± 0.1% and 90.0 ± 0.2%, respectively (p < 0.001), while ethanol extracts of Ulva rigida (Chlorophyta) had the greatest potential to stimulate GLP-1 secretion and GLP-1 synthesis (p < 0.001). A water extract of Porphyra linearis (Rhodophyta) significantly reduced the overall glycaemic excursion during an oral glucose tolerance test in normal mice (p < 0.05). These results demonstrate future potential for common edible seaweeds to be used as medicinal foods or bio-therapeutics to tackle type 2 diabetes mellitus by targeting GLP-1 secretion, DPP-4 activity or alpha-glucosidase activity.

Pharmacodynamic Functions of Synthetic Derivatives for Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis.

Drug resistant bacteria have emerged, so robust methods are needed to evaluate combined activities of known antibiotics as well as new synthetic compounds as novel antimicrobial agents to treatment efficacy in severe bacterial infections. Marine natural products (MNPs) have become new strong leads in the drug discovery endeavor and an effective alternative to control infections. Herein, we report the bioassay guided fractionation of marine extracts from the sponges Lendenfeldia, Ircinia, and Dysidea that led us to identify novel compounds with antimicrobial properties. Chemical synthesis of predicted compounds and their analogs has confirmed that the proposed structures may encode novel chemical structures with promising antimicrobial activity against the medically important pathogens. Several of the synthetic analogs exhibited potent and broad spectrum in vitro antibacterial activity, especially against the Methicillin-resistant Staphylococcus aureus (MRSA) (MICs to 12.5 μM), Mycobacterium tuberculosis (MICs to 0.02 μM), uropathogenic Escherichia coli (MIC o 6.2 μM), and Pseudomonas aeruginosa (MIC to 3.1 μM). Checkerboard assay (CA) and time-kill studies (TKS) experiments analyzed with the a pharmacodynamic model, have potentials for in vitro evaluation of new and existing antimicrobials. In this study, CA and TKS were used to identify the potential benefits of an antibiotic combination (i.e., synthetic compounds, vancomycin, and rifampicin) for the treatment of MRSA and M. tuberculosis infections. CA experiments indicated that the association of compounds 1a and 2a with vancomycin and compound 3 with rifampicin combination have a synergistic effect against a MRSA and M. tuberculosis infections, respectively. Furthermore, the analysis of TKS uncovered bactericidal and time-dependent properties of the synthetic compounds that may be due to variations in hydrophobicity and mechanisms of action of the molecules tested. The results of cross-referencing antimicrobial activity, and toxicity, CA, and Time-Kill experiments establish that these synthetic compounds are promising potential leads, with a favorable therapeutic index for antimicrobial drug development.