Bioactive Products Research Articles

Metagenomic mining of two Egyptian Red Sea sponges associated microbial community

The Red Sea is a promising habitat for the discovery of new bioactive marine natural products. Sponges associated microorganisms represent a wealthy source of compounds with unique chemical structures and diverse biological activities. Metagenomics is an important omics-based culture-independent technique that is used as an effective tool to get genomic and functional information on sponge symbionts. In this study, we used metagenomic analysis of two Egyptian Red Sea sponges Hyrtios erectus and Phorbas topsenti microbiomes to study the biodiversity and the biosynthetic potential of the Red Sea sponges to produce bioactive compounds. Our data revealed high biodiversity of the two sponges’ microbiota with phylum Proteobacteria as the most dominant phylum in the associated microbial community with an average of 31% and 70% respectively. The analysis also revealed high biosynthetic potential of sponge Hyrtios erectus microbiome through detecting diverse types of biosynthetic gene clusters (BGCs) with predicted cytotoxic, antibacterial and inhibitory action. Most of these BGCs were predicted to be novel as they did not show any similarity with any MIBiG database known cluster. This study highlights the importance of the microbiome of the collected Red Sea sponge Hyrtios erectus as a valuable source of new bioactive natural products.

Asperinsuterpenes A-C from the Fungus Aspergillus insuetus BTBU20220155.

Three new meroterpenoids, asperinsuterpenes A-C (1-3), and eight previously reported natural products, namely asnovolin I (4), (2'E,4'E,6'E)-6-(1'-carboxyocta-2',4',6'-triene)-9-hydroxydrim-7-ene-11,12-olide (5), (2'E,4'E,6'E)-6-(1'-carboxyocta-2',4',6'-triene)-11,12-epoxy-9,11-dihydroxydrim-7-ene (6), cinereain (7), carnequinazolines A and B (8 and 9), carnemycin B (10), and stromemycin (11) were isolated from the fungus Aspergillus insuetus, strain BTBU20220155. The structures of the compounds were determined based on spectroscopic techniques, including 1D and 2D NMR, HRESIMS, and ECD experiments. The in vitro antimicrobial evaluation revealed that compounds 5 and 11 exhibited inhibitory activity against Candida albicans, with minimum inhibitory concentration (MIC) values of 12.5 and 25 μg/mL, respectively. These findings suggest that A. insuetus is a promising source of bioactive natural products with potential applications in antifungal therapy.

Exploiting UPO versatility to transform rutin in more soluble and bioactive products

The discovery of unspecific peroxygenases (UPOs) completely changed the paradigm of enzyme-based oxyfunctionalization reactions, as these enzymes can transform a wide variety of substrates with a relatively simple reaction mechanism. The fact that UPO can exert both peroxygenative and peroxidative activity in either aromatic or aliphatic carbons, represents a great potential in the production of high value-added products from natural antioxidants. In this work, the flavonoid rutin has been considered as possible substrate for UPO from Agrocybe aegerita, and its peroxygenation or its peroxidation and successive oligomerization have been studied. Different experiments were performed in order to reduce the range of process variables involved and gaining insight on the behavior of this enzyme, leading to a multivariable optimization of UPO-based rutin modification. While trying to preserve enzyme activity this optimization aimed for maximizing the production of more soluble antioxidants. Reusability of the enzyme was evaluated recovering UPO using an enzymatic membrane reactor, revealing challenges in enzyme stability due to inactivation during the filtration stages. The influence of the radical scavenger ascorbic acid on product formation was investigated, revealing its role in directing the reaction towards hydroxylated rutin derivatives, hence indicating a shift towards more soluble and bioactive products.

Non-benzenoid N-aryl oxalamide: synthesis of troponyl-oxalamide peptides by Pd(II)-catalyzed C(sp3)-H functionalization of glycinamides.

Aryl oxalamides are constituents of various promising drug-like molecules. Their aryl groups are derived from the benzenoid aromatic moiety. However, non-benzenoid aromatic molecules, troponoids, are found in various bioactive natural products. It would be thought-provoking to explore non-benzenoid aryl oxalamide derivatives. This report describes the synthesis of N-troponyl-oxalamide peptides by Pd(II)-catalyzed C(sp3)-H functionalization of N-troponyl glycinate peptides. This is the first instance of β-hydride elimination at the palladium complex of N-troponyl glycinates that generates imine in situ, rendering the synthesis of oxalamides. Importantly, the crystal structures of representative oxalamide derivatives form distinctive foldameric structures, such as β-sheet type structures, owing to the presence of additional troponyl carbonyl groups. Hence, these non-benzenoid oxalamides are potential scaffolds for tuning the structure and function of N-troponyl peptides, which could provide innovative avenues of research in the development of emerging structural and functional peptides.

Chemical composition, functional properties, physico-chemical properties, and techno-functional characteristics of Satureja protein hydrolysate stabilized in a gelatin matrix.

The current evaluation was conducted to investigate the chemical composition and functional properties of protein hydrolysates from different Satureja species. The major amino acids (mg/100 g protein) in the protein from different Satureja species were arginine (6.06-14.37), asparagine (1.39-17.06), glutamine (2.42-11.60), glutamic acid (6.34-9.32), beta-aminoisobutyric acid (3.31-10.29), alanine (4.64-9.59), aspartic acid (5.73-9.54), proline (4.25-8.14), leucine (3.63-5.69), serine (2.64-4.83), lysine (1.89-4.56), glycine (0.96-5.27), valine (2.76-4.83), and phenylalanine (2.86-3.75). Protein hydrolysates from Satureja species exhibited comparable antioxidant activity (IC50 = 0.270-0.328 mg/mL), anti-linoleic acid oxidation (IC50 = 0.231-0.301 mg/mL), anti-lecithin oxidation (IC50 = 0.198-0.258 mg/mL), anti-starch oxidation (IC50 = 0.201-0.277 mg/mL), anti-amylase activity (IC50 = 0.314-0.337 mg/mL), and anti-lipase activity (IC50 = 0.309-0.369 mg/mL). The physico-chemical properties of gelatin dispersion were electrical conductivity (1197 microsiemens/cm), osmolarity (190 milliosmol/kg), surface tension (45 mN/m), particle size (179 nm), zeta potential (-48 mV), and viscosity (4.92 mPa.s). Techno-functional characteristics of freeze-dried gelatin particles were as follows: water content (7.68%), water solubility (84.57%), water swelling (151.33%), hygroscopicity (38.20%), hydrophobicity (6.50 μg/g), emulsification activity (68.54%), emulsification stability (57.86%), foam expansion activity (56.08%), foam stability (41.84%), oil-holding capacity (1.96 g/g), and water-holding capacity (4.45 g/g). Protein hydrolysate causes minor changes in the physico-chemical and techno-functional properties of gelatin. The current investigation introduces Satureja protein hydrolysate as a possible functional and techno-functional ingredient for bioactive food products for treating diabetes and oxidative stress and as a natural preservative for the food industry.

Brassicaceae Mustards: Phytochemical Constituents, Pharmacological Effects, and Mechanisms of Action against Human Disease.

The Brassicaceae genus consists of many economically important mustards of value for food and medicinal purposes, namely Asian mustard (Brassica juncea), ball mustard (Neslia paniculata), black mustard (B. nigra), garlic mustard (Alliaria petiolata), hedge mustard (Sisymbrium officinale), Asian hedge mustard (S. orientale), oilseed rape (B. napus), rapeseed (B. rapa), treacle mustard (Erysimum repandum), smooth mustard (S. erysimoides), white ball mustard (Calepina irregularis), white mustard (Sinapis alba), and Canola. Some of these are commercially cultivated as oilseeds to meet the global demand for a healthy plant-derived oil, high in polyunsaturated fats, i.e., B. napus and B. juncea. Other species are foraged from the wild where they grow on roadsides and as a weed of arable land, i.e., E. repandum and S. erysimoides, and harvested for medicinal uses. These plants contain a diverse range of bioactive natural products including sulfur-containing glucosinolates and other potentially valuable compounds, namely omega-3-fatty acids, terpenoids, phenylpropanoids, flavonoids, tannins, S-methyl cysteine sulfoxide, and trace-elements. Various parts of these plants and many of the molecules that are produced throughout the plant have been used in traditional medicines and more recently in the mainstream pharmaceutical and food industries. This study relates the uses of mustards in traditional medicines with their bioactive molecules and possible mechanisms of action and provides an overview of the current knowledge of Brassicaceae oilseeds and mustards, their phytochemicals, and their biological activities.

Ready Access to [5,6,5]-Trioxa-spiro and Fused Ketals via Ag-Catalyzed Cascade Annulation of 4-Pentyn-1-ols and Aldehydes.

In this study, we unveil the versatility of 4-pentyn-1-ols as carbonyl surrogates for the unprecedented synthesis of diverse oxygen heterocycles, including [5,6,5]-bis-spiroketals (trioxadispiroketals) and [5,6,5]-furano-spiroketals related to bioactive natural products. These reactions commence with the π-activation-induced intramolecular hydroalkoxylation of 4-pentyn-1-ols, yielding cyclic enol ethers, which undergo subsequent three-component annulation with aldehydes in a [2+2+1+1] fashion, resulting in the formation of [5,6,5]-bis-spiroketals. Notably, the distinctive steric features of alkynyl alcohols, particularly those with a secondary or tertiary alcohol functionality, dictate divergent reaction pathways, leading to the formation of [5,6,5]-furano-spiroketals.

Research Progress and Biosynthetic Mechanisms of Nutritional Compounds Obtained from Various Organs During the Developmental Stages of a Medicinal Plant (Chinese Jujube).

The fruit of the jujube tree is high in nutrients and has various health benefits. China is a major producer of jujube, and it is now cultivated all around the world. Numerous studies have demonstrated the nutritional value and potential health advantages of bioactive compounds found in the jujube tree. Furthermore, the jujube tree has a remarkable 7000-year agricultural history. The jujube plant has developed a rich gene pool, making it a valuable resource for germplasm. Different studies have focused on the developmental stages of jujube fruits to identify the optimal time for harvest and to assess the changes in their bioactive natural compounds or products during the process of development but the molecular mechanism underlying the production of bioactive natural products in Z. jujuba is still poorly understood. Moreover, the potential differential expressed genes (DEGs) identified as responsible for the synthesis of these compounds should be further functionally verified. It has been noticed that the contents of total flavonoids, total phenolic, and vitamin C increase significantly during the ripening process, while the contents of soluble sugars and organic acids decrease gradually. In this review, we have also scrutinized the challenges that hinder the utilization of jujube fruit resources and suggested potential areas for further research. As such, our review serves as a valuable resource for the future development of jujube-based nutritional compounds and the incorporation of their nutritional elements into the functional foods industry.

Qualitative Analysis of Bioactive Compounds from different Polypores from Kolhapur District

It is now widely recognized that biological activity occurs throughout the fungal kingdom. Since ancient times so called mushrooms belonging to Basidiomycota have been used for medicinal purpose. Various bioactive compounds show important biological activities such as antioxidative, free radical scavenging, anticarcinogenic, immunomodulatory, antiviral, and antibacterial etc. In earlier times, mushrooms were originally regarded as a significant source of medicinal in oriental regions. Discovering new major medicines is becoming a great challenge for scientific community. The present study deals with qualitative analysis and identifies the different classes of bioactive compounds as well as their potential therapeutic properties in three different polypores viz. Earliella scabrosa, Podoscypha petalodes and Polyporus grammocephalous. This information can provide insight about the bioactivity and metabolite production from these Polypore fungi, which can potentially lead to the development of new drugs. Keywords: Bioactive compounds, Polypores fungi, Therapeutic properties

Phytohormone-induced changes in growth, physiology, and biochemistry of Aurantiochytrium sp. for sustainable bioproduction

The study aimed to assess the effects of nine combinations of phytohormones, salicylic acid (SA), gibberellic acid (GA), and jasmonic acid (JA) on the growth, physiology, and biochemistry of Aurantiochytrium sp. Parameters like optical density (OD), biomass, protein content, hydrogen peroxide (H2O2), malondialdehyde (MDA), catalase activity (CAT), and gene expression (malic enzyme (ME) and acetyl-CoA carboxylase (ACCase)) were assessed at various cultivation stages (24, 48, 72, and 96 h). The research also analyzed fatty acid composition, unsaturated fatty acids (UFA), saturated fatty acids (SFA), and the UFA to SFA ratio (USS) to understand the biochemical changes induced by phytohormones. Results demonstrated that modifying phytohormone concentrations significantly affected the characteristics of the microalgae, particularly in correlation with different growth stages, emphasizing the necessity of precise control of phytohormone levels for optimizing cultivation conditions and enhancing bioactive compound production in Aurantiochytrium sp.

Enhanced astaxanthin production in Haematococcus lacustris by electrochemical stimulation of cyst germination

This study investigated the technical feasibility of using electrogermination to activate dormant cysts as an inoculum for subsequent 14-d photosynthetic astaxanthin production in Haematococcus lacustris. Electrotreatment affected the cell viability, surface charge, and morphology of H. lacustris cysts. At an optimal voltage of 2 V for 60 min, the cyst germination rate peaked at 44.6 % after 1 d, representing a 2.2-fold increase compared with that of the untreated control. Notably, electrogermination significantly enhanced both the astaxanthin content (44.9 mg/g cell) and productivity (13.2 mg/L/d) after 14 d of photobioreactor cultivation, corresponding to 1.7- and 1.5-fold increases compared with those in control, respectively. However, excessive electrotreatment, particularly at voltages exceeding 2 V or for durations beyond 60 min, did not enhance the astaxanthin production capability of H. lacustris. Proper optimization of renewable electrogermination can enable sustainable algal biorefinery to produce multiple bioactive products without compromising cell viability and astaxanthin productivity.

An Acid Catalyzed Alkynyl‐Prins Cyclization‐Rearrangement Cascade of 2‐(Alkynol)Benzoates: An Approach to 3‐Alkyl‐[n,5]‐Oxaspirophthalides

AbstractThe oxaspiro‐phthalides ([n,5]‐oxaspirobenzalactones) bearing a phthalide spirofused to a cyclic‐ether of various sizes are frameworks found in bioactive natural products. The discovery and development of an alkynyl‐Prins cyclization based, strategy for the construction of structurally interesting, medicinally useful [5,5]‐[6,5]‐, and [7,5]‐oxaspirophthalides is reported in this manuscript. Our strategy represents a report on the construction of oxaspiro‐phthalides using the alkynyl‐Prins cyclization. This approach exhibits broad substrate scope with respect to carbonyl compounds and 2‐(alkynol)benzoates, with yields ranging between 43–98%. Isolation of intermediate, and further conversion of it to the end‐product supported the proposed mechanistic pathway.

Bioactive Compound Production in Yerba Mate Clones with Increasing Nitrogen in Semi-Hydroponic System

Bioactive Compound Production in Yerba Mate Clones with Increasing Nitrogen in Semi-Hydroponic System

Genome mining for ribosomally synthesized and post-translationally modified peptides (RiPPs) in Streptomyces bacteria

Ribosomally synthesized post-translationally modified peptides (RiPPs) are a novel category of bioactive natural products (NPs). Streptomyces bacteria are a potential source of many bioactive NPs. Limited opportunities are available to characterize all the bioactive NP gene clusters. In this study, 410 sequences of Streptomyces were analyzed for RiPPs through genome mining using the National Center for Biotechnology Information (NCBI), by combining BAGEL and anti-SMASH. A total of 4098 RiPPs were found; including both classified (lanthipeptide, RiPP-like, bacteriocin, LAPs, lassopeptide, thiopeptides) and nonclassified RiPPs. Soil was identified as a rich habitat for RiPPs. These data may offer alternative future remedies for various health issues.

Inhibitory mechanism of 4-ethyl-1,2-dimethoxybenzene produced by Streptomyces albidoflavus strain ML27 against Colletotrichum gloeosporioides

Actinomycetes have emerged as significant biocontrol resources due to their rich array of bioactive natural products. While much research has historically focused on secondary metabolites isolated from their fermentation broth, there remains a dearth of reports on their volatile organic compounds (VOCs). Here, strain ML27, isolated from soil, was identified as Streptomyces albidoflavus based on morphological features, physiological, biochemical, and molecular characteristics (16S rRNA, atpD, recA, and rpoB gene sequences). VOCs from S. albidoflavus strain ML27 were effectively captured using solid-phase microextraction (SPME) and tentatively identified through gas chromatography–mass spectrometry (GC/MS). Among these compounds, 4-ethyl-1,2-dimethoxybenzene exhibited broad-spectrum antifungal activity and demonstrated efficacy in controlling citrus anthracnose, with a control efficacy of 86.67%. Furthermore, the inhibitory mechanism of 4-ethyl-1,2-dimethoxybenzene against Colletotrichum gloeosporioides was revealed. Results indicated that 4-ethyl-1,2-dimethoxybenzene induced swelling, deformity, and breakage in C. gloeosporioides mycelia, and significantly inhibited spore germination. Transcriptome analysis revealed that 4-ethyl-1,2-dimethoxybenzene inhibited the growth and development of C. gloeosporioides primarily by disrupting energy metabolism and the integrity of the cell wall and membrane. Based on these results, it is promising to develop 4-ethyl-1,2-dimethoxybenzene as a novel biopesticide for controlling citrus anthracnose.

Formulation of novel functional extrudates containing natural bioactive compounds

Incorporating natural antimicrobial agents into food systems is a promising alternative to synthetic additives. This study developed corn-based functional extrudates enriched with essential oils from oregano, rosemary, chamomile, and hypericum (EOB) via twin screw extrusion processing. EOB was introduced in both encapsulated and non-encapsulated forms using electrohydrodynamic processing, spray drying, and freeze drying within a whey protein isolate and pullulan matrix. Extrudates containing spray-dried EOB (SP-EOB) achieved the highest extrusion efficiency (72.94% ± 1.16%). Morphological analysis revealed homogeneous structures for XE and XS extrudates, while XF extrudates were more porous. The gastrointestinal release kinetics of EOB from the extrudates were best described by the Korsmeyer-Peppas model, indicating an anomalous diffusion mechanism with “n” values ranging from 0.480 to 0.650. These findings highlight the potential for naturally bioactive and sustainable food products via advanced processing methods, reducing dependence on synthetic additives.

An integrative metabolomics and metagenomics analysis of functional microbiota examines the extraction of bioactive products using longan pericarp

Longan (Dimocarpus longan Lour.) is a nutrient-rich fruit, widely cultivated in China. However, its seeds and pericarp, often discarded as waste, are rich in bioactive components, particularly polyphenolics. In this research, we develop microbiota-assisted extraction technique, which is efficient and environmentally friendly for extracting these valuable components. These results showcased superior efficiency in the diversity and richness of extracted bioactive components, although yielding slightly lower TP content than ethanol extraction. The active components extracted by microbiota-assisted extraction technique increased to 2.45 mg/g, which was higher 2.13 times and 3.10 times compared to optimized ethanol and water extraction, respectively. The numbers of active components extracted by these three methods were 39, 24 and 30, separately, and Quercetin 3-D-xyloside and Kaempferol 3-O-alpha-L-rhamnopyranosyl were identified in longan pericarp extracts by microbiota-assisted extraction. Metagenomics analysis revealed stable and diverse microbiota with functional capabilities for enhancing extraction efficiency. Functional annotations indicated significant roles in biosynthesis, carbohydrate degradation, and fatty acid metabolism. Microbiota-assisted extracts exhibited a broad spectrum of bioactive compounds with potential health benefits, including antioxidant and anti-inflammatory properties. These results provide a theoretical foundation for developing sustainable extraction technologies.

Effect of pomegranate solution alone or combined with chlorhexidine against oral multispecies biofilm.

Natural bioactive products have been tested as alternative antimicrobial agents. This study evaluated the effect of Punica granatum extract (PGE) on oral multispecies biofilms. Lyophilized extracts from pomegranate peel were prepared, and the punicalagin content was assessed by ultra-performance liquid chromatography (UPLC). Oral multispecies biofilms from 2 donors were grown on four collagen-coated hydroxyapatite discs. After incubation for 7 days or 3 weeks, the biofilms were exposed to water (control), 2% CHX, 10% PGE, 20% PGE or 30% PGE for 3 min. The proportions of dead bacteria were assessed by the live/dead staining and confocal microscopy. After the analysis, the best PGE concentration (30%) was combined with CHX. The experimental phases were repeated using water, 2% CHX, 30% PGE and 30% PGE + 2% CHX. Five random areas of the biofilm on each disc were scanned, resulting in 20 scanned areas for each group. Regarding the biofilm volume, no differences were found amongst solutions (p = .111). The PGE solution killed bacteria effectively in 1-week, 2-week and 3-week-old-plaque biofilms, ranging from 37 to 55.3%, depending on the PGE concentration. The 30% PGE (a) (p = .0009) had greater antibiofilm effectiveness than 2% CHX (b), which killed bacteria in the 25.2 to 48.7% range. The 10% and 20% PGE had intermediate values (ab), without significant differences from 30% PGE (p = 1.002). Water (c) had the lowest proportion of dead bacteria (p < .00001) in a range of 5 to 6.7% and lower effectiveness in killing bacteria (p < .05). The PGE alone or mixed with 2% CHX had greater anti-biofilm effectiveness than CHX (p < .05). The old plaque biofilms were more resistant than the 7-day-old plaque (p < .05). The 30% PGE (alone or combined with CHX) exhibited a greater antibiofilm effect on oral multispecies biofilms grown on hydroxyapatite discs than 2% CHX.

Combining three-dimensionality and CaP glass-PLA composites: Towards an efficient vascularization in bone tissue healing

Bone regeneration often fails due to implants/grafts lacking vascular supply, causing necrotic tissue and poor integration. Microsurgical techniques are used to overcome this issue, allowing the graft to anastomose. These techniques have limitations, including severe patient morbidity and current research focuses on stimulating angiogenesis in situ using growth factors, presenting limitations, such as a lack of control and increased costs. Non-biological stimuli are necessary to promote angiogenesis for successful bone constructs. Recent studies have reported that bioactive glass dissolution products, such as calcium-releasing nanoparticles, stimulate hMSCs to promote angiogenesis and new vasculature. Moreover, the effect of 3D microporosity has also been reported to be important for vascularisation in vivo. Therefore, we used room-temperature extrusion 3D printing with polylactic acid (PLA) and calcium phosphate (CaP) based glass scaffolds, focusing on geometry and solvent displacement for scaffold recovery. Combining both methods enabled reproducible control of 3D structure, porosity, and surface topography. Scaffolds maintained calcium ion release at physiological levels and supported human mesenchymal stem cell proliferation. Scaffolds stimulated the secretion of vascular endothelial growth factor (VEGF) after 3 days of culture. Subcutaneous implantation in vivo indicated good scaffold integration and blood vessel infiltration as early as one week after. PLA-CaP scaffolds showed increased vessel maturation 4 weeks after implantation without vascular regression. Results show PLA/CaP-based glass scaffolds, made via controlled 3D printing, support angiogenesis and vessel maturation, promising improved vascularization for bone regeneration.

Potential skin anti-aging effects of main phenolic compounds, tremulacin and tremuloidin from Salix chaenomeloides leaves on TNF-α-stimulated human dermal fibroblasts

The genus Salix spp. has long been recognized as a healing herb for its use in treating fever, inflammation, and pain relief, as well as a food source for its nutritional value. In this study, we aimed to explore the potential bioactive natural products in the leaves of Salix chaenomeloides, commonly known as Korean pussy willow, for their protective effects against skin damage, including aging. Utilizing LC/MS-guided chemical analysis of the ethanol extract of S. chaenomeloides leaves, with a focus on major compounds, we successfully isolated two main phenolic compounds, tremulacin (1) and tremuloidin (2). Subsequently, we investigated the protective effects of tremulacin (1) and tremuloidin (2) in TNF-α-stimulated human dermal fibroblasts (HDFs). The results revealed that both tremulacin (1) and tremuloidin (2) inhibited TNF-α-stimulation-induced ROS, suppressed matrix metalloproteinase-1 (MMP-1) expression, and enhanced collagen secretion. This implies that both tremulacin (1) and tremuloidin (2) hold promise as preventive agents against photoaging-induced skin aging. Furthermore, we assessed the activity of mitogen-activated protein kinases (MAPKs), cyclooxygenase-2 (COX-2), and heme oxygenase 1 (HO-1) to elucidate the mechanism of photoaging inhibition by tremuloidin (2), which exhibited superior efficacy. We found that tremuloidin (2) inhibited ERK and p38 phosphorylation and notably suppressed COX-2 expression while significantly upregulating HO-1 expression. These findings suggest potent anti-inflammatory and antioxidant properties of tremuloidin (2), positioning it as a potential candidate for combating photoaging-induced skin aging.