Mutanofactin promotes adhesion and biofilm formation of cariogenic Streptococcus mutans.

Cariogenic Streptococcus mutans is known as a predominant etiological agent of dental caries due to its exceptional capacity to form biofilms. From strains of S. mutans isolated from dental plaque, we discovered, in the present study, a polyketide/nonribosomal peptide biosynthetic gene cluster, muf, which directly correlates with a strong biofilm-forming capability. We then identified the muf-associated bioactive product, mutanofactin-697, which contains a new molecular scaffold, along with its biosynthetic logic. Further mode-of-action studies revealed that mutanofactin-697 binds to S. mutans cells and also extracellular DNA, increases bacterial hydrophobicity, and promotes bacterial adhesion and subsequent biofilm formation. Our findings provided an example of a microbial secondary metabolite promoting biofilm formation via a physicochemical approach, highlighting the importance of secondary metabolism in mediating critical processes related to the development of dental caries.

Bioactive Peptides: Synthesis, Sources, Applications, and Proposed Mechanisms of Action.

Bioactive peptides are a group of biological molecules that are normally buried in the structure of parent proteins and become active after the cleavage of the proteins. Another group of peptides is actively produced and found in many microorganisms and the body of organisms. Today, many groups of bioactive peptides have been marketed chemically or recombinantly. This article reviews the various production methods and sources of these important/ubiquitous and useful biomolecules. Their applications, such as antimicrobial, antihypertensive, antioxidant activities, blood-lipid-lowering effect, opioid role, antiobesity, ability to bind minerals, antidiabetic, and antiaging effects, will be explored. The types of pathways proposed for bioactive applications will be in the next part of the article, and at the end, the future perspectives of bioactive peptides will be reviewed. Reading this article is recommended for researchers interested in various fields of physiology, microbiology, biochemistry, and nanotechnology and food industry professionals.

Screening and quantification of anti-quorum sensing and antibiofilm activity of Actinomycetes isolates against food spoilage biofilm-forming bacteria.

BACKGROUND: Biofilms can form in many industries, one of them is the food industry. The formation of biofilms in this industry could cause immense economic losses and endanger public health. Biofilms formation is mainly triggered by quorum sensing. Therefore, inhibition of quorum sensing could be an innovative approach to inhibit the formation of biofilms. One way to inhibit quorum sensing is by using anti-quorum sensing compounds. Actinomycetes are a group of bacteria that is acknowledged to produce these compounds. RESULTS: There were eight crude extracts of Actinomycetes isolates that showed promising anti-quorum sensing activity against Chromobacterium violaceum. The concentration of the crude extracts was 20 mg/mL. All the crude extracts showed no antibacterial activity against food spoilage bacteria, except for crude extracts of isolate 18 PM that showed antibacterial activity against Bacillus subtilis. They also showed various antibiofilm activity, both inhibition and destruction. The highest inhibition and destruction activity sequentially was done by crude extracts of isolate 12 AC with 89.60% against Bacillus cereus and crude extracts of isolate SW03 with 93.06% against Shewanella putrefaciens. CONCLUSIONS: Actinomycetes isolates that isolated from different regions in Indonesia can be used as potential candidates to overcome biofilms formed by food spoilage bacteria using their ability to produce anti-quorum sensing compounds.

Eustigmatophyte strains with potential interest in cancer prevention and treatment: partial chemical characterization and evaluation of cytotoxic and antioxidant activity.

The interest in bioactive compounds from microalgae is increasing since they have medicinal and nutritional areas. The present work aims to evaluate the potential pharmaceutical interest of extracts from three eustigmatophyte strains from the Coimbra Collection of Algae (ACOI): Chlorobotrys gloeothece, Chlorobotrys regularis and Characiopsis aquilonaris. Antioxidant and antiproliferative activities were determined as well as chlorophyll a, carotenoid and phenolic total contents. In addition, major pigments and sterols were identified and quantified. The three strains were grown until the stationary phase and then the biomass was extracted. Antioxidant activity was measured by TEAC, DPPH and FRAP assays and antiproliferative effect was assessed by the MTT method on MCF-7, PC-3 and NHDF cells. The pigment and phenolic total contents were determined by spectrophotometry. Of these strains, C. aquilonaris showed the highest antioxidant activity measured by TEAC and FRAP assays (23.98 ± 0.01 µmol TE eq g-1 DW and 42.57 ± 0.04 µmol TE eq g-1 DW, respectively), a selective effect in reduting MCF-7 cells proliferation and a larger amount of chlorophyll a, carotenoids and phenolic content (18.40 ± 0.00 µg chlorophyll a mg-1 DW, 2.27 ± 0.00 mg carotenoids g-1 DW and 6.23 ± 0.01 mg GAE g-1 DW, respectively). A positive correlation between chlorophyll a and TEAC assay was observed, as well as between carotenoids and TEAC and FRAP assays, suggesting these compounds as important contributors to significant antioxidant activity. Violaxanthin, cholesterol and stigmasterol were present in larger amount in C. aquilonaris while C. regularis showed a higher amount of ß-carotene. These results suggest that these three ACOI eustigmatophytes are promising for applications in the improvement of human health, particularly in cancer prevention and treatment.

Chemical Diversity and Biological Activity of Secondary Metabolites from Soft Coral Genus Sinularia since 2013.

Sinularia is one of the conspicuous soft coral species widely distributed in the world's oceans at a depth of about 12 m. Secondary metabolites from the genus Sinularia show great chemical diversity. More than 700 secondary metabolites have been reported to date, including terpenoids, norterpenoids, steroids/steroidal glycosides, and other types. They showed a broad range of potent biological activities. There were detailed reviews on the terpenoids from Sinularia in 2013, and now, it still plays a vital role in the innovation of lead compounds for drug development. The structures, names, and pharmacological activities of compounds isolated from the genus Sinularia from 2013 to March 2021 are summarized in this review.

Green-lipped (greenshell™) mussel (Perna canaliculus) extract supplementation in treatment of osteoarthritis: a systematic review.

OBJECTIVES: Intervention studies using New Zealand green-lipped or greenshell™ mussel (GSM) (Perna canaliculus) extract in osteoarthritis (OA) patients have shown effective pain relief. This systematic review summarises the efficacy of GSM extracts in the treatment of OA. METHODS: A literature search of the three databases EMBASE, MEDLINE, and Scopus was performed to identify relevant articles published up to March 2020. Inclusion criteria were clinical trials published in English measuring the effect of supplementation of whole or a lipid extract from GSM on pain and mobility outcomes in OA patients. RESULTS: A total of nine clinical trials were included in systematic review, from which five studies were considered appropriate for inclusion in a forest plot. Pooled results showed that GSM extracts (lipid extract or whole powder) provide moderate and clinically significant treatment effects on a visual analogue scale (VAS) pain score (effect size: - 0.46; 95% CI - 0.82 to - 0.10; p = 0.01). The whole GSM extract improved gastrointestinal symptoms in OA patients taking anti-inflammatory medications. The GSM extract was considered to be generally well tolerated in most of the studies. CONCLUSION: The overall analysis showed that GSM provided moderate and clinically meaningful treatment effects on OA pain. However, the current evidence is limited by the number and quality of studies, and further larger and high-quality studies are needed to confirm the effectiveness and to identify the optimal GSM format. Nevertheless, it is worth considering using GSM extracts especially for patients seeking alternative pain relief treatments with fewer side effects compared to conventional treatment.

Immunomodulatory properties of characellide A on human peripheral blood mononuclear cells.

Marine sponges and their associated microbiota are multicellular animals known to produce metabolites with interesting pharmacological properties playing a pivotal role against a plethora of pathologic disorders such as inflammation, cancer and infections. Characellide A and B belong to a novel class of glycolipopeptides isolated from the deep sea marine sponge Characella pachastrelloides. In this study, we have evaluated the effects of characellide A and B on cytokine and chemokine release from human peripheral blood mononuclear cells (PBMC). Characellide A induces a concentration- and time-dependent CXCL8, IL-6 and TNF-α release from PBMC. This production is mediated by the induction of gene transcription. Moreover, cytokine/chemokine release induced by characellide A from PBMC is CD1d-dependent because a CD1d antagonist, 1,2-bis(diphenylphosphino)ethane [DPPE]-polyethylene glycolmonomethylether [PEG], specifically inhibits characellide A-induced activation of PBMC. In conclusion, characellide A is a novel modulator of adaptative/innate immune responses. Further studies are needed to understand its potential pharmacological application.

Chemical Evaluation, Antioxidant, Antiproliferative, Anti-Inflammatory and Antibacterial Activities of Organic Extract and Semi-Purified Fractions of the Adriatic Sea Fan, Eunicella cavolini.

Due to sedentary lifestyle and harsh environmental conditions, gorgonian coral extracts are recognized as a rich source of novel compounds with various biological activities, of interest to the pharmaceutical and cosmetic industries. The presented study aimed to perform chemical screening of organic extracts and semi-purified fractions obtained from the common Adriatic gorgonian, sea fan, Eunicella cavolini (Koch, 1887) and explore its abilities to exert different biological effects in vitro. Qualitative chemical evaluation revealed the presence of several classes of secondary metabolites extended with mass spectrometry analysis and tentative dereplication by using Global Natural Product Social Molecular Networking online platform (GNPS). Furthermore, fractions F4 and F3 showed the highest phenolic (3.28 ± 0.04 mg GAE/g sample) and carotene (23.11 ± 2.48 mg ß-CA/g sample) content, respectively. The fraction F3 inhibited 50% of DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) and ABTS (2,2'-azino-bis (3-ethylbenzthiazolin-6-yl) sulfonic acid) radicals at the concentrations of 767.09 ± 11.57 and 157.16 ± 10.83 µg/mL, respectively. The highest anti-inflammatory potential was exhibited by F2 (IC50 = 198.70 ± 28.77 µg/mL) regarding the inhibition of albumin denaturation and F1 (IC50 = 254.49 ± 49.17 µg/mL) in terms of soybean lipoxygenase inhibition. In addition, the most pronounced antiproliferative effects were observed for all samples (IC50 ranging from 0.82 ± 0.14-231.18 ± 46.13 µg/mL) against several carcinoma cell lines, but also towards non-transformed human fibroblasts pointing to a generally cytotoxic effect. In addition, the antibacterial activity was tested by broth microdilution assay against three human pathogenic bacteria: Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The latter was the most affected by fractions F2 and F3. Finally, further purification, isolation and characterization of pure compounds from the most active fractions are under investigation.

Protein biomarker elucidation for the verification of biological agents in the taxonomic group of Gammaproteobacteria using tandem mass spectrometry.

Some pathogenic microbes can be used for nefarious applications and instigate population-based fear. In a bio-threat scenario, rapid and accurate methods to detect biological agents in a wide range of complex environmental and clinical matrices, is of paramount importance for the implementation of mitigation protocols and medical countermeasures. This study describes targeted and shot-gun tandem MS based approaches for the verification of biological agents from the environmental samples. The marker proteins and peptides were elucidated by an exhaustive literature mining, in silico analysis of prioritized proteins, and MS/MS analysis of abundant proteins from selected bacterial species. For the shot-gun methodology, tandem MS analysis of abundant peptides was carried from spiked samples. The validation experiments employing a combination of shot-gun tandem MS analysis and a targeted search reported here is a proof of concept to show the applicability of the methodology for the unambiguous verification of biological agents at sub-species level, even with limited fractionation of crude protein extracts from environmental samples.

Pink oyster mushroom Pleurotus flabellatus mycelium produced by an airlift bioreactor-the evidence of potent in vitro biological activities.

Four types of mycelial extracts were derived from the airlift liquid fermentation (ALF) of Pleurotus flabellatus, namely exopolysaccharide (EX), endopolysaccharide (EN), hot water (WE), and hot alkali (AE) extracts. Such extracts were screened for their active components and biological potential. EN proved to be most effective in inhibition of lipid peroxidation (EC50 = 1.71 ± 0.02 mg/mL) and in Cupric ion reducing antioxidant capacity (CUPRAC) assay (EC50 = 2.91 ± 0.01 mg TE/g). AE exhibited most pronounced ability to chelate ferrous ions (EC50 = 4.96 ± 0.08 mg/mL) and to scavenge ABTS radicals (EC50 = 3.36 ± 0.03 mg TE/g). ß-glucans and total phenols contributed most to the chelating ability and quenching of ABTS radicals. Inhibition of lipid peroxidation correlated best with total glucans, total proteins, and ß-glucans. Total proteins contributed most to CUPRAC antioxidant capacity. Antifungal effect was determined against Candida albicans ATCC 10231 (MIC: 0.019-0.625 mg/mL; MFC: 0.039-2.5 mg/mL), and towards C. albicans clinical isolate (MIC and MFC: 10.0-20.0 mg/mL). Comparison of cytotoxicity against colorectal carcinoma HCT 116 cells (IC50: 1.8 ± 0.3-24.6 ± 4.2 mg/mL) and normal lung MRC-5 fibroblasts (IC50: 17.0 ± 4.2-42.1 ± 6.1 mg/mL) showed that EN, and especially AE possess selective anticancer activity (SI values 3.41 and 9.44, respectively). Slight genotoxicity was observed only for AE and EX, indicating the low risk concerning this feature. Notable antioxidative and anticandidal activities, selective cytotoxicity against colorectal carcinoma cells, and absence/low genotoxicity pointed out that ALF-cultivated P. flabellatus mycelium could be considered as a valuable source of bioactive substances.

UPLC-MS/MS Identification and Quantification of Withanolides from Six Parts of the Medicinal Plant Datura Metel L.

Withanolides from six parts (flower, leaf, stem, root, seed, and peel) of Datura metel L. (D metel L.) obtained from ten production areas in China were identified and quantified by UPLC-MS/MS. A total of 85 withanolides were characterized for the first time using the UPLC-Q-TOF-MS/MS system. Additionally, a simultaneous, rapid and accurate measurement method was developed for the determination of 22 bioactive withanolides from ten production areas with the UPLC-Q-TRAP-MS/MS system. The results show the total withanolide content is highest in the leaves (155640.0 ng/g) and lowest in the roots (14839.8 ng/g). Compared with other production areas, the total content of plants from Dujiangyan was the highest at 82013.9 ng/g (value range of ten areas: 82013.9-42278.5 ng/g). The results also show significant differences in the distribution of withanolides in the different plant parts, as well as across different production areas. This is a breakthrough report providing a simultaneous qualitative and quantitative analysis of 22 withanolides in D. metel L. It could be the basis for the more rational use of various parts of D. metel L., and the expansion of medicinal resources. This work also lays a solid foundation for research on the quality control of D. metel L.

Utilisation/upgrading of orange peel waste from a biological biorefinery perspective.

Orange peel waste (OPW) (peels, pulp and seeds) is an underutilised residue coming from the orange juice industry. Its classical applications are cattle feeding and composting, while they cannot ensure a total use of OPW, so landfilling is also common practice. On the other side, OPW is very rich in sugars, polysaccharides, essential oils and polyphenols, so there is a vast literature focused on the development and optimization of technologies and processes to several products from OPW. In this review, papers on OPW-based bioprocesses are visited, discovering a wide landscape that goes from the composting and biogas processes on detoxified OPW (deoiled) to bioprocesses to bioethanol, chemicals, flavours and polymers. All these processes are prone to integration within the 2nd-generation biorefinery framework.

Marine-Derived Natural Compounds for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons, leading to the motor dysfunctions of patients. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progress was revealed to be associated with the abnormal aggregation of α-synuclein, the elevation of oxidative stress, the dysfunction of mitochondrial functions, and the increase of neuroinflammation. However, current anti-PD therapies could only produce symptom-relieving effects, because they could not provide neuroprotective effects, stop or delay the degeneration of dopaminergic neurons. Marine-derived natural compounds, with their novel chemical structures and unique biological activities, may provide anti-PD neuroprotective effects. In this study, we have summarized anti-PD marine-derived natural products which have shown pharmacological activities by acting on various PD targets, such as α-synuclein, monoamine oxidase B, and reactive oxygen species. Moreover, marine-derived natural compounds currently evaluated in the clinical trials for the treatment of PD are also discussed.

Nutritional Composition, Anti-Diabetic Properties and Identification of Active Compounds Using UHPLC-ESI-Orbitrap-MS/MS in Mangifera odorata L. Peel and Seed Kernel.

Mangifera odorata fruit, the hybrid forms between M. indica (mango) and M. foetida (bacang), has been shown to exhibit potential antioxidant activity, and the fruit waste could demonstrate functional and nutritional potential. In the present study, the nutritional composition (proximate, sugars, vitamins and minerals analyses), the anti-diabetic activities and phytochemical profile of M. odorata peel and seed kernel were investigated for the first time. The results indicated that seed kernel rich in fat, protein, carbohydrate, and ash while peel contained significantly greater amount of fiber, minerals, ß-Carotene and ascorbic acid compared to seed kernel. The samples were then extracted using different solvents (acetone, ethanol, methanol at 60%, v/v and pure deionized water) and their anti-diabetic activities (α-amylase and α-glucosidase inhibition assay) were determined. Seed kernel had the lowest IC50 values for α-amylase and α-glucosidase inhibition assay in 60% ethanol and 60% acetone, respectively. Due to the toxic effect and high volatility of acetone, the ethanolic extracts of samples were further analyses for their phytochemical profile using high performance liquid chromatography-mass spectrometry (LC-MS) and ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry (UHPLC-ESI-Orbitrap-MS/MS). The most abundant compounds identified were phenolic acid, ellagic acid, and flavonoid. These findings suggest that M. odorata fruit wastes, especially the seed kernel possesses promising ability to be used as functional ingredient in the food industry.

Chemically-Induced Production of Anti-Inflammatory Molecules in Microalgae.

Microalgae have been widely recognized as a valuable source of natural, bioactive molecules that can benefit human health. Some molecules of commercial value synthesized by the microalgal metabolism have been proven to display anti-inflammatory activity, including the carotenoids lutein and astaxanthin, the fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), and sulphated polysaccharides. These molecules can accumulate to a certain extent in a diversity of microalgae species. A production process could become commercially feasible if the productivity is high and the overall production process costs are minimized. The productivity of anti-inflammatory molecules depends on each algal species and the cultivation conditions, the latter being mostly related to nutrient starvation and/or extremes of temperature and/or light intensity. Furthermore, novel bioprocess tools have been reported which might improve the biosynthesis yields and productivity of those target molecules and reduce production costs simultaneously. Such novel tools include the use of chemical triggers or enhancers to improve algal growth and/or accumulation of bioactive molecules, the algal growth in foam and the surfactant-mediated extraction of valuable compounds. Taken together, the recent findings suggest that the combined use of novel bioprocess strategies could improve the technical efficiency and commercial feasibility of valuable microalgal bioproducts production, particularly anti-inflammatory compounds, in large scale processes.

Cacolides: Sesterterpene Butenolides from a Southern Australian Marine Sponge, Cacospongia sp.

Chemical analysis of a marine sponge, Cacospongia sp. (CMB-03404), obtained during deep sea commercial fishing activities off the southern coast of Australia, yielded an unprecedented family of sesterterpene α-methyl-γ-hydroxybutenolides, cacolides A⁻L (1⁻12), together with biosynthetically related norsesterterpene carboxylic acids, cacolic acids A⁻C (13⁻15). Structures were assigned on the basis of detailed spectroscopic analysis with comparisons to known natural products and biosynthetic considerations. In addition to revealing new chemical diversity, this study provided a valuable platform for comparing and contrasting the capabilities of the traditional dereplication technologies of HPLC-DAD, HPLC-MS and NMR, with those of the emerging HPLC-MS/MS approach known as global natural products social molecular networking (GNPS), as applied to marine sponge sesterterpene tetronic acids.

Stress-Driven Discovery of New Angucycline-Type Antibiotics from a Marine Streptomyces pratensis NA-ZhouS1.

Natural products from marine actinomycetes remain an important resource for drug discovery, many of which are produced by the genus, Streptomyces. However, in standard laboratory conditions, specific gene clusters in microbes have long been considered silent or covert. Thus, various stress techniques activated latent gene clusters leading to isolation of potential metabolites. This study focused on the analysis of two new angucycline antibiotics isolated from the culture filtrate of a marine Streptomyces pratensis strain NA-ZhouS1, named, stremycin A (1) and B (2) which were further determined based on spectroscopic techniques such as high resolution time of flight mass spectrometry (HR-TOF-MS), 1D, and 2D nuclear magnetic resonance (NMR) experiments. In addition, four other known compounds, namely, 2-[2-(3,5-dimethyl-2-oxo-cyclohexyl)-6-oxo-tetrahydro-pyran-4yl]-acetamide (3), cyclo[l-(4-hydroxyprolinyl)-l-leucine] (4), 2-methyl-3H-quinazoline-4-one (5), and menthane derivative, 3-(hydroxymethyl)-6-isopropyl-10,12-dioxatricyclo[7.2.1.0]dodec-4-en-8-one (6) were obtained and elucidated by means of 1D NMR spectrometry. Herein, we describe the "Metal Stress Technique" applied in the discovery of angucyclines, a distinctive class of antibiotics that are commonly encoded in microbiomes but have never been reported in "Metal Stress" based discovery efforts. Novel antibiotics 1 and 2 exhibited antimicrobial activities against Pseudomonas aeruginosa, methicillin resistant Staphylococcus aureus (MRSA), Klebsiella pneumonia, and Escherichia coli with equal minimum inhibitory concentration (MIC) values of 16 µg/mL, while these antibiotics showed inhibition against Bacillus subtilis at MIC value of approximately 8⁻16 µg/mL, respectively. As a result, the outcome of this investigation revealed that metal stress is an effective technique in unlocking the biosynthetic potential and resulting production of novel antibiotics.

Marine Microalgae: Promising Source for New Bioactive Compounds.

The study of marine natural products for their bioactive potential has gained strength in recent years. Oceans harbor a vast variety of organisms that offer a biological and chemical diversity with metabolic abilities unrivalled in terrestrial systems, which makes them an attractive target for bioprospecting as an almost untapped resource of biotechnological applications. Among them, there is no doubt that microalgae could become genuine "cell factories" for the biological synthesis of bioactive substances. Thus, in the course of inter-laboratory collaboration sponsored by the European Union (7th FP) into the MAREX Project focused on the discovery of novel bioactive compounds of marine origin for the European industry, a bioprospecting study on 33 microalgae strains was carried out. The strains were cultured at laboratory scale. Two extracts were prepared for each one (biomass and cell free culture medium) and, thus, screened to provide information on the antimicrobial, the anti-proliferative, and the apoptotic potential of the studied extracts. The outcome of this study provides additional scientific data for the selection of Alexadrium tamarensis WE, Gambierdiscus australes, Prorocentrum arenarium, Prorocentrum hoffmannianum, and Prorocentrum reticulatum (Pr-3) for further investigation and offers support for the continued research of new potential drugs for human therapeutics from cultured microalgae.

Bioactive Compounds from Marine-Derived Aspergillus, Penicillium, Talaromyces and Trichoderma Species.

The impact of bioactive compounds from natural sources on human life, particularly in pharmacology and biotechnology, has challenged the scientific community to explore new environmental contexts and the associated microbial diversity. [...].

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.