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Oligosaccharide and peptide extracts obtained separately from defatted rapeseed meal (DRM) have shown antiproliferative activities on the MCF-7 breast cancer cell line. However, oligosaccharide extracts were not tested on human fibroblasts and have low yields. The objective of the present study was to combine two antiproliferative extracts, the peptides and oligosaccharides, that were obtained independently with commercial enzymes from DRM, allowing improvement of the mass yield and antiproliferative activity. The DRM was solubilized in an alkaline medium to obtain an insoluble meal residue (IMR) and an alkaline extract (RAE). To produce the oligosaccharide extract from IMR, three enzymes and different enzyme/substrate ratios were used. The oligosaccharide extract (molecular weight <30 kDa) recovered with the commercial enzyme. Endogalacturonase showed an 80% inhibition on MCF-7 cells at 20 mg/mL. The combination of this oligosaccharide extract with the peptide extract (obtained with Alkalase 2.4 L from a RAE at 10 mg/mL) inhibited 84.3% of MCF-7 cells proliferation at a concentration of 20 mg/mL, exhibiting no cytotoxic effects on fibroblasts. The mass yield of the extract pool was 27.07% (based on initial DRM). It can be concluded that a mixture of antiproliferative extracts was produced from DRM which was selective against MCF-7 cells.

It is accepted that the medicinal use of complex mixtures of plant-derived bioactive compounds is more effective than purified bioactive compounds due to beneficial combination interactions. However, synergy and antagonism are very difficult to study in a meticulous fashion since most established methods were designed to reduce the complexity of mixtures and identify single bioactive compounds. This study represents a critical review of the current scientific literature on the combined effects of plant-derived extracts/bioactive compounds. A particular emphasis is provided on the identification of antimicrobial synergistic or antagonistic combinations using recent metabolomics methods and elucidation of approaches identifying potential mechanisms that underlie their interactions. Proven examples of synergistic/antagonistic antimicrobial activity of bioactive compounds are also discussed. The focus is also put on the current challenges, difficulties, and problems that need to be overcome and future perspectives surrounding combination effects. The utilization of bioactive compounds from medicinal plant extracts as appropriate antimicrobials is important and needs to be facilitated by means of new metabolomics technologies to discover the most effective combinations among them. Understanding the nature of the interactions between medicinal plant-derived bioactive compounds will result in the development of new combination antimicrobial therapies.

Nearly 20 years ago, the first report appeared on the discovery of a novel genus—Muscodor. This organism was isolated as an endophyte from a cinnamon tree that had been introduced to Honduras from Sri Lanka in the early part of the last century. Characteristically, the original Muscodor albus, and all of its species isolated since that time are non-spore producers and each one exudes a characteristic spectrum of volatile bioactive compounds. The majority have a whitish mycelium, which is sometimes coiling, intertwined and decorated with variously shaped structures. Presently, there are at least 22 type species known/documented and each has been described as an endophyte from various plant families with widely varying habitats. An enormous variety of volatile organic compounds (VOCs) are produced by Muscodor spp. and some of these include esters, acids, aldehydes, ketones, aromatics, alkanes, alcohols, nitrosamides and terpenoids. The VOCs are both inhibitory and lethal to a wide variety of fungi and bacteria including some major pathogens of plants and humans. Interestingly, in almost all cases studied, no one compound by itself can mimic the bioactivity of the complete gas mixture, suggesting that the volatiles are acting in a synergistic manner and this has been tested with individual as well as the VOCs in various mixtures and concentrations. This review will discuss some of the recent findings in all aspects of this unique fungal genus whilst at the same time pointing out some of the major questions that remain about its biology, ecology and its applications in agriculture, medicine and other sectors. Most importantly, the authors provide arguments supporting the claim that Muscodor is taxonomically distinct from Induratia, a recently proposed change to its nomenclature.

Honey is a complex and variable mixture that contains more than 180 biochemical compounds from various molecule families. This mixture is obtained after processing the nectar out of plant food sources at the level of the bee abdomen. The bioactive components found in this natural product are in charge of its antimicrobial properties. Honey is used for its antibacterial actions against Gram-positive (Gram+) and Gram-negative (Gram-) bacteria, its anti-fungal and antimycotic actions against moulds and yeasts, along with its protozoal and antiviral activities. This literature review outlines the natural antimicrobial potential of honey; it explains the factors responsible for this potential and spells out their mechanisms of action. Osmotic pressure, water activity, the acid content of honey, presence of bioactive compounds like hydrogen peroxide (H2O2), phenolic acids, flavonoids, methylglyoxal (MGO), defensin-1, lysozyme, volatile compounds as well as antibacterial products secreted from the lactic bacteria that are behind this antimicrobial activity. This potential basically depends on the biological activities of the initially harvested floral source, its geographical origin, season, storage conditions, honey age, health of bee colonies and suitable beekeeping practices.

Eclipta prostrata (L.) is an important and well-known medicinal plant due to its valuable bioactive compounds. Microorganisms, including arbuscular mycorrhizal fungi (AMF), and salinity could directly impact plant metabolome, thus influencing their secondary metabolites and the efficacy of herbal medicine. In this study, the role of different single AMF species ( Funneliformis mosseae , Septoglomus deserticola , Acaulospora lacunosa ) and a mixture of six AMF species in plant growth and physio-biochemical characteristics of E. prostrata under non-saline conditions was investigated. Next, the most suitable AM treatment was chosen to examine the impact of AMF on physio-biochemical features and polyphenol profiles of E. prostrata under saline conditions (100 and 200 mM NaCl). The findings indicated that AMF mixture application resulted in more effective promotion on the aboveground part of non-saline plants than single AMF species. AM mixture application improved growth and salt tolerance of E. prostrata through increasing the activity of catalase, peroxidase (at 4 weeks), proline, and total phenolic content (at 8 weeks). Such benefits were not observed under high salinity, except for a higher total phenolic concentration in mycorrhizal plants at 8 weeks. Through high-performance liquid chromatography, 14 individual phenolic compounds were analyzed, with wedelolactone and/or 4,5-dicaffeoylquinic acid abundant in all treatments. Salinity and mycorrhizal inoculation sharply altered the polyphenol profiles of E. prostrata . Moderate salinity boosted phenolic compound production in non-AM plants at 4 weeks, while at 8 weeks, the decline in the content of phenolic compounds occurred in uncolonized plants subjected to both saline conditions. Mycorrhization augmented polyphenol concentration and yield under non-saline and saline conditions, depending on the growth stages and salt stress severity. Plant age influenced polyphenol profiles with usually a higher content of phenolic compounds in older plants and changed the production of individual polyphenols of both non-AM and AM plants under non-stress and salt stress conditions. A better understanding of factors (involving mycorrhiza and salinity) affecting the phenolic compounds of E. prostrata facilitates the optimization of individual polyphenol production in this medicinal plant.

Marine actinomycetes are a promising source for developing new antiviral agents for plant diseases, as they produce a wide variety of bioactive compounds. To date, antiviral activity of marine actinomycetes against plant viruses are rare. The present study proceeded to identify and characterize promising antiviral actinomycetes from Red Sea in Hurghada, Egypt, control Cucumber Mosaic Virus (CMV) and, profile the individual chemical components of bioactive crude extracts. Biological and molecular characterization was performed to identify CMV isolate using RT-PCR and coat protein (CP) gene nucleotide sequences analysis. In squash plants, antiviral, CMV optical density, biochemical responses, and resistance genes expression of Streptomyces extracts (SE1 and SE2) were performed against CMV by disease incidence, severity (%) assays, ELISA technique, physiological analysis, and real-time quantitative PCR (qPCR). Chemical profiling of the two Streptomyces extracts was investigated using GC–MS analysis. Antiviral activity was performed by curative (C), protective (P), and inactivation (I) techniques under greenhouse conditions. The obtained results of the morphological, biochemical, physiological and molecular level studies of the Streptomycetes isolates ph6 and MARH showed similarity towards the species of Streptomyces and identified as Streptomyces variabilis strain ph6 (OQ283766) and Streptomyces sp. strain MARH (OQ283775). Protective treatments (P: SE1 and P: SE2) resulted in disease suppression of 100%, while curative treatments (C: SE1 and C: SE2) by 87% and 100%, and inactivation treatments (I: SE1 and I: SE2) by approximately 70%, and 80% respectively compared to mock-inoculated plants. The absorbance values of ELISA at 405 nm for P: SE1 and P: SE2 were 0.191 ± 0.02, and 0.187 ± 0.00 respectively compared to CMV-infected plants which recorded 0.854 ± 0.00. Levels of ascorbate peroxidase (APX), catalase (CAT) enzymes, proline content, total photosynthetic pigments, and total phenolic compounds were significantly increased in P: SE1 and P: SE2 treated squash plants compared to CMV-infected plants. Moreover, P: SE1 and P: SE2 increased membrane stabilization and reduced electrolyte leakage. The pathogenesis-related (PR) gene such as PR-b1 was overexpressed by about 3.09-, and 10.37-fold increases and PR-2 by 1.07-, and 1.66-fold increases for P: SE1 and P: SE2 respectively compared to the CMV-infected control group. Chemical profiling of the ethyl acetate extracts of Streptomyces variabilis and Streptomyces sp. MARH authenticated the presence of constituents such as 1,3¬Dinitro¬2-imidazolidinone (42.60%), Nephthoside-1,2’,3’,4’-Tetraacetate (76.18%), Tetraphenylporphyrinato dichlorotitanium(IV) (12.42%) and L-Lysine (17.01%) respectively. Our results showed that Streptomyces variabilis and Streptomyces sp. MARH are promising strains for production of antiviral natural products, increasing the phenolic compounds, activity of the antioxidant enzymes, and induction the expression of pathogenesis-related genes to generate systemic acquired resistance (SAR) in squash plants. They also supported the potential use of their extracts as an environmentally friendly novel bio-virocides to sustainably stop the spread of plant viruses.

Mango seed kernel, a by-product of the processing industry, can be valorized as a potential source of bioactive compounds. Binary mixtures of ethanol and water, used in solid–liquid extraction (SLE), have drawn interest as an effective means of recovering phytochemicals from plant materials because these solvents can be used in food applications and their synergistic effect makes them a superior solvent over their pure counterparts. Total phenolic content (TPC) and HPLC chromatograms of each ethanolic extract revealed that ethanol concentration had a significant effect on phenolic compound recovery, wherein, TPC of mango kernel varied from 18.19 to 101.68 mg gallic acid equivalence (GAE) per gram of sample. Subsequently, the antioxidant activities (AOAc) of the extracts, measured by scavenging activities with the DPPH+ (1,1-diphenyl-2-picrylhydrazyl) radical and ferric reducing antioxidant power (FRAP) assay, ranged from 8.19 to 85.45 mmol/L and 3.82–55.61 mmol/L Trolox equivalence, respectively. The solvent containing 50% (w/w) ethanol–water had the highest TPC and exhibited the most potent reducing and radical scavenging activities. With the use of an HPLC–UV/Vis, gallic acid, caffeic acid, rutin and penta-O-galloyl-β-d-glucose were identified to be present in the mango seed kernel. Results show that the mango seed kernel is a viable source of bioactive compounds which can be recovered with water–ethanol binary solvent systems.

The health risks associated with synthetic preservatives have intensified the search for natural antimicrobial alternatives. Crocus sativus L. (saffron) generates abundant by-products, such as tepals and leaves, which are rich in bioactive compounds with demonstrated antimicrobial potential. Compared to other natural alternatives, saffron by-products offer distinct advantages, including a unique combination of phenolic compounds (e.g., ellagic acid, rutin) and carotenoids (e.g., crocin) that act synergistically against both Gram-positive and Gram-negative bacteria, as well as fungi. Additionally, these by-products represent a sustainable solution, with approximately 63 kg of agricultural waste generated per kg of saffron spice. This study optimized the antibacterial and antifungal efficacy of saffron extracts using a simplex centroid mixture design. Phytochemical analysis using high-performance liquid chromatography with diode-array detection (HPLC–DAD) identified key antimicrobial compounds, including ellagic acid (68.43% in leaves, 50.31% in tepals) and crocin (9.59% in stigmas). Antimicrobial assays against Staphylococcus aureus , Escherichia coli , Candida albicans , and Geotrichum candidum revealed that stigma extracts exhibited superior antibacterial activity (MIC = 25 mg/mL for S. aureus and E. coli ), while tepal and leaf extracts showed promising antifungal effects (MIC = 12.5 mg/mL for G. candidum ). The mixture design approach uncovered synergistic interactions, with an equimolar combination of stigma, tepal, and leaf extracts (33:33:33) demonstrating the strongest antibacterial activity (MIC = 25 mg/mL) and a ternary mixture (34% stigma, 30% leaf, 36% tepal) achieving the lowest antifungal MIC (6.25 mg/mL). These findings highlight saffron by-products as highly effective and sustainable natural antimicrobials, providing a cost-efficient (40–60% reduction compared to conventional extracts) and multi-functional alternative to synthetic preservatives. Their dual functionality (antimicrobial + natural coloring) and agricultural waste origin make them particularly valuable for industrial applications in food preservation, pharmaceuticals, and biopharmaceuticals. The integration of statistical modeling maximizes their potential, meeting the growing demand for safe, natural antimicrobial solutions with clear competitive advantages

In nature, bacteria can form biofilms, multi-layered structures that adhere microbial populations to solid surfaces by exopolysaccharides, proteins, and nucleic acids. In addition to causing foodborne infections, biofilms can be a major problem in aquaculture. Actinomycetes extracts have previously demonstrated antibiofilm activity against multiple foodborne and fish pathogens, and further characterization of these extracts is needed. In this study, we identified the chemical structures and antibiofilm properties of four extracts and determined the genetic similarity of the isolates to known Streptomyces isolates. We found that several extracts contained multiple antibiofilm compounds, and the antibiofilm activities of all extracts were most stable at pH 6. Furthermore, the antibiofilm inhibition and destruction activities of the isolates were stable at different temperatures. All of crude extracts demonstrated activity against biofilms formed by foodborne and fish pathogens on the surface of stainless-steel coupons as well as polystyrene that commonly used in industrial equipment. Using PCR 16S-rRNA gene and DNA sequencing analysis, the four Actinomycetes isolates were found to be 99% (1 AC), 97% (20 PM), 95% (16 PM), and 85% (18 PM) similar to Streptomyces . Biofilm structure were analyzed using Scanning Electron Microscopy coupled with Energy-Dispersive Spectrometry analysis. Coniine/(S)-2-propylpiperidine was the most active fraction of the crude extracts of the 1 AC, 20 PM, and 16 PM isolates, and piperidine, 2-(tetrahydro-2-furanyl) was most active in the 18 PM isolate.

Marine microalgae are considered a potentially new and valuable source of biologically active compounds for applications in several biotechnology sectors. They can be easily cultured, have short generation times and enable an environmentally-friendly approach to drug discovery by overcoming problems associated with the over-utilization of marine resources and the use of destructive collection practices. Considering the increasing rate of antibiotic-resistance bacteria and infections by fungi, 46 microalgae have been screened in this study for possible antibacterial and antifungal activities. Two different extraction methods have been used in order to increase the probability of finding positive hits. In particular, we screened microalgae in both control and nutrient stress conditions. We also tested different strains for 7 species in order to study potentially different bioactivities due to strain diversity. Results showed that extracts of two diatoms, Skeletonema costatum and Chaetoceros pseudocurvisetus , had anti-tuberculosis activity and were active only when cultured in the control and phosphate-starvation conditions, while the nitrogen starvation condition showed no activity. In addition, we tested both the organic and water extracts and found that only the organic extracts for both diatoms were active. The organic extracts of these two diatom species were not toxic on normal human cell lines.