Search Results (92)

Microalgae are extremely diverse photosynthetic organisms, adapted to live in different habitat conditions, from freshwater to marine environments. This adaptability is also associated with the ability to produce several metabolites. Polyunsaturated aldehydes (PUAs), first identified in 1999 in Thalassiosira gravida and Skeletonema costatum, are known to influence the development of their predators, having teratogenic effects and blocking their development. PUAs have shown several activities, such as antitumor, antimicrobial and antiparasite. Another relevant compound is pheophorbide a (PPBa), a chlorophyll degradation product, which has previously shown properties useful to be considered as a photosensitizer in photodynamic therapy, demonstrating cytotoxic effects on various tumor cell lines. It has also been shown to have activity against some bacteria and fungi. Considering the growing problem of multi-antibiotic resistance of human pathogenic bacteria and the increasing market demand for new drugs, the aim of our work was to screen two PUAs, i. e., 2,4-octadienal and trans,trans-2,4-decadienal, and PPBa against a panel of human pathogenic bacteria and fungi: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Aspergillus fumigatus. The antimicrobial activity was evaluated through MIC (Minimum Inhibitory Concentration) and MFC/MBC (Minimum Fungicidal/Bactericidal Concentration), demonstrating that the two PUAs had a greater antimicrobial activity than PPBa on both bacteria and fungi, except for P. aeruginosa, where the antimicrobial activity was low. The compound 2,4-Octadienal showed extremely high antifungal activity, especially against the fungus A. fumigatus, where the MIC and MFC were 0.001 µL/mL and 0.004 µL/mL, respectively. These results are shedding light on the antimicrobial activity of microalgal compounds and their possible applications for different human infection diseases. Full article

To date, exploration of Gracilaria and Gelidiella’s bioactive compounds has been conducted using conventional methods that require a long time, high costs, and significant effort. Currently, metabolomic profiling and molecular networking have emerged as methods of exploring bioactive compounds. This study aimed to perform bioactive compound profiling through a metabolomic LC-HRMS-based and molecular networking approach in Gelidiella acerosa, Gracilaria arcuata, and Gracilaria verrucosa. All chromatograms and MS/MS spectra obtained for three crude extracts were digitally converted into an mzXML file using MSConvert, submitted to the Global Natural Product Social (GNPS), and visualized in Cytoscape 3.9.1. In total, nine dereplicated compounds were identified: 11-Deoxyprostaglandin (m/z 324.214), Diacylglyceryl trimethylhomoserines (DGTS) (m/z 684.575), Glycochenodeoxy acid (m/z 448.369), Lysophosphatidylcholine (m/z 522.350), Diacylglyceryl trimethylhomoserines (DGTS) (m/z 656.557), Pheophorbide A (m/z 593.266), Pyropheophorbide A (m/z 593.266), (2R,3R)-2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-2,3-dihydro-4H-chromen-4-one (m/z 303.15), and Polyporic acid (m/z 293.156). These compounds are typically classified as fatty acids, lipids, terpenoids, alkaloids, shikimates, and phenylpropanoids. The molecular networking and metabolite clustering showed an interesting pattern where some compounds were produced only by one species, some by two species, and some by all three. These compounds may have pharmaceutical potential based on their chemical properties and reported activities. Full article

The Pheophorbide a oxygenase (PaO) is a key enzyme in chlorophyll degradation and plays an important role in plant senescence. However, the PaO gene’s function in sorghum remains underexplored. In this study, we identified five SbPaO gene family members in the sorghum genome through bioinformatics analysis. Analyses of gene structure, phylogeny, and collinearity revealed high conservation of this gene family among grass crops, suggesting similar functions. Subcellular localization and protein network predictions indicated that SbPaOs may participate in chlorophyll catabolism and regulate leaf senescence. Expression pattern analysis showed that SbPaO1, SbPaO3, SbPaO4, and SbPaO5 were highly expressed in leaves and significantly upregulated during senescence. Haplotype analysis found three SbPaO genes significantly linked to thousand-grain weight (TGW); superior haplotypes SbPaO1-hap4, SbPaO3-hap5, and SbPaO4-hap4 notably increased this trait. Single-gene improvements increased TGW by 10.57–17.20%, dual-gene aggregation by 18.78–24.75%, and three-gene aggregation by 29.09%. The study also developed Kompetitive Allele-Specific PCR (KASP) markers that identify superior haplotypes with 100% accuracy. In summary, this study’s results provide a theoretical basis and genetic resources for further exploration of haplotype pyramiding strategies to breed new high-yielding sorghum varieties and delineate a clear research direction for subsequent functional validation and breeding practices. Full article

Marine diatoms are prolific producers of bioactive metabolites, but Arctic species remain underexplored as sources of antibacterial and antibiofilm agents. Here, seven species were grown in photobioreactors (PBRs) and systematically screened for antibacterial, antibiofilm, and cytotoxic activities. All strains inhibited Gram-positive bacteria, and four reduced Staphylococcus epidermidis biofilm formation. Porosira glacialis emerged as a lead species, combining potent antibiofilm activity with favourable traits for large-scale cultivation, and no detectable cytotoxicity. Bioactivity-guided fractionation of P. glacialis yielded two antibiofilm compounds: methyl 3-hydroxyoctadecanoate, the first time reported in diatoms and newly associated with antibiofilm bioactivity, and pheophorbide a, a chlorophyll degradation product. Both inhibited S. epidermidis biofilm formation without any observed cytotoxicity. Notably, Cylindrotheca closterium exhibited cultivation-dependent antibiofilm activity, underscoring the importance of growth conditions for metabolite production. These findings highlight the potential of Arctic diatoms as a sustainable source of antibiofilm agents and support further exploration of their metabolites for antimicrobial and industrial applications. Full article

Food spoilage and contamination are major global challenges, reducing food quality, safety, and availability, causing significant economic losses. This study evaluates the photodynamic and sonodynamic antibacterial activities of grape leaf extracts from Beer and Hanut Orcha varieties. The extracts were tested against Staphylococcus aureus and Escherichia coli under illumination and ultrasonic activation. The results demonstrated that the photodynamic and sonodynamic treatments significantly enhanced the antibacterial efficacy of the extracts when higher concentrations of the extracts and prolonged exposure led to complete bacterial eradication. Separation of the extracts using RP-18 cartridges (Yicozoo Energy Technology Co., Ltd., Xi’an, China) enabled us to get an active fraction containing components responsible for antimicrobial effects. Singlet oxygen generation measurements confirmed the involvement of reactive oxygen species in bacterial inactivation under illumination. Using HPLC/MS, the active components responsible for the photodynamic properties of the extracts were identified as quercetin 3’-O-glucuronide and pheophorbide a. The findings suggest that these natural extracts, in combination with photodynamic and sonodynamic activation, represent promising alternatives to conventional antibiotics. Further studies should focus on the isolation of active individual compounds, the improvement of treatment parameters, and the investigation of molecular mechanisms to facilitate the development of practical applications in medicine and food preservation. Full article

Chlorophyll, the green pigment essential for photosynthesis, abundantly found in green vegetables and algae, has attracted growing scientific interest for its potential therapeutic effects, particularly in diabetes management. Recent research highlighted that chlorophyll and its derivatives may beneficially influence glucose metabolism and oxidative stress, key factors in diabetes. This review examines current knowledge on how chlorophyll compounds could aid diabetes control. Chlorophyll and its derivatives appear to support glucose regulation primarily through actions in the gastrointestinal tract. They modulate gut microbiota, improve glucose tolerance, reduce inflammation, and alleviate obesity-related markers. While chlorophyll itself does not directly inhibit digestive enzymes like α-glucosidase, its derivatives such as pheophorbide a, pheophytin a, and pyropheophytin a may slow carbohydrate digestion, acting as α-amylase and α-glucosidase inhibitors, reducing postprandial glucose spikes. Additionally, chlorophyll enhances resistant starch content, further controlling glucose absorption. Beyond digestion, chlorophyll derivatives show promise in inhibiting glycation processes, improving insulin sensitivity through nuclear receptor modulation, and lowering oxidative stress. However, some compounds pose risks due to photosensitizing effects and toxicity, warranting careful consideration. Chlorophyllin, a stable semi-synthetic derivative, also shows potential in improving glucose and lipid metabolism. Notably, pheophorbide a demonstrates insulin-mimetic activity by stimulating glucose uptake via glucose transporters, offering a novel therapeutic avenue. Overall, the antioxidant, anti-inflammatory, and insulin-mimicking properties of chlorophyll derivatives suggest a multifaceted approach to diabetes management. While promising, these findings require further clinical validation to establish effective therapeutic applications. Full article

Photosynthesis in plants and the electron transport chain in mitochondria are examples of life-sustaining electron transfer processes. The benzoquinones plastoquinone and ubiquinone are key components of these pathways that cycle through their oxidized and reduced forms. Previously, we reported direct photoreduction of biologically relevant quinones mediated by photosensitizers, red light and electron donors. Herein we examined direct photoreduction of the quinone imine 2,6-dichlorophenolindophenol (DCPIP) using red light, methylene blue as the photosensitizer and ethylenediaminetetraacetic acid (EDTA) as the electron donor. Photoreduction of DCPIP by methylene blue and EDTA was very pH-dependent, with three-fold enhanced rates at pH 6.9 vs. pH 7.4. Photochemical redox cycling of DCPIP produced hydrogen peroxide via singlet oxygen-dependent reoxidation of reduced DCPIP. Histidine enhanced photoreduction by scavenging singlet oxygen, whereas increased molecular oxygen exposure slowed DCPIP photoreduction. Attempts to photoreduce DCPIP with pheophorbide A, a chlorophyll metabolite, and triethanolamine as the electron donor in 20% dimethylformamide were unsuccessful. Photoreduced benzoquinones including 2,3-dimethoxy-5-methyl-p-benzoquinone (CoQ₀), methoxy-benzoquinone and methyl-benzoquinone were used to examine electron transfer to DCPIP. For photoreduced CoQ₀ and methoxy-benzoquinone, electron transfer to DCPIP was rapid and complete, whereas for reduced methyl benzoquinone, it was incomplete due to differences in reduction potential. Nonetheless, electron transfer from photoreduced quinols to DCPIP is a rapid and sensitive method to investigate quinone photoreduction by chlorophyll metabolites. Full article

In this article, the synthesis and characterization of chlorin-based photosensitizers for potential applications in photodynamic therapy (PDT) of triple-negative breast cancer (TNBC) are described. The photodynamic efficacy of the synthesized chlorin-desthiobiotin (CDBTN) conjugate and its zinc and indium complexes were compared with the starting unconjugated precursor methyl pheophorbide, and assessed in a TNBC cell line in vitro. The chlorin-desthiobiotin complex aims to target the vitamin receptors upregulated in malignant cancer cells. The synthesized CDBTN was combined with chemotherapeutic agents (paclitaxel, cisplatin or fluorouracil) to evaluate their binary photodynamic efficacy. Cell survival assay in vitro indicated that the chlorin-vitamin conjugate CDBTN—alone and in combination with paclitaxel or fluorouracil—is photoactive against the TNBC cell line, but not when combined with cisplatin. The combination index (CI) calculated using the Chou-Talalay method indicated synergism of CDBTN and fluorouracil combination, aligning with the in vitro assay. The photodynamic cytotoxicity of CDBTN was also evaluated in vivo using the hydra as a novel model organism. This study is the first to show the use of the aquatic hydra organism in assessing photodynamic activity of the photosensitizer alone or in combination with chemotherapeutic agents. In vivo results with hydras indicated that the CDBTN-cisplatin combination is more phototoxic than CDBTN-paclitaxel or CDBTN-fluorouracil binary treatment. With the proper adjustment of concentration and light dosage, the synthesized photosensitizer can provide promising application in binary chemotherapy PDT treatment of TNBC. Full article

Background: Interleukin-15 (IL-15) stimulates the proliferation of natural killer cells or T cells, which, in combination with photodynamic therapy (PDT), has emerged as an effective strategy for cancer photoimmunotherapy. Instead of direct cytokine receptor activation, IL-15 necessitates first binding to the IL-15 receptor α chain subunit (IL-15Rα), followed by trans-presentation to the IL-15 receptor β/γ chain subunit on the effector cells for pharmacologic activation. Therefore, the delivery of IL-15 remains a major challenge owing to its short half-life, its lack of targeting activity, and the limited availability of IL-15Rα. Methods: A co-hitchhiking delivery approach using recombinant IL-15 (rIL-15) and a photosensitizer, pheophorbide A (PhA), is developed for enhanced combinatorial cancer immunotherapy with PDT. A recombinant IL-15Rα-sushi-Fc fusion protein (rILR-Fc) is designed to load rIL-15 through the IL-15Rα sushi domain, which mimics its trans-presentation. Moreover, the Fc moiety of rILR-Fc can load PhA based on its high binding affinity. Results: Through self-assembly, rILR-Fc/PhA/rIL-15 nanoparticles (NPs) are formulated to co-hitchhike PhA and rIL-15, which improves the tumor accumulation of PhA and rIL-15 through receptor-mediated transcytosis. Moreover, the nanoparticles prolong the blood half-life of rIL-15 but do not alter the elimination rate of PhA from the blood. The rILR-Fc/PhA/rIL-15 NPs effectively elicit potent systemic antitumor immunity and long-lasting immune memory against tumor rechallenge in model mice bearing orthotopic colon tumors. Conclusions: The enhanced antitumor therapeutic effect demonstrates that the co-hitchhiking delivery strategy, optimizing the pharmacokinetics of both the photosensitizer and IL-15, provides a promising strategy for combinatorial photodynamic and IL-15 immunotherapy. Full article

Foxtail millet is a characteristic miscellaneous grain crop with many benefits in current agricultural production and is crucial in the adjustment of the planting structure and the sustainable development of dry farming. However, the harmful effects of weeds have become a critical challenge, restricting the modern production of foxtail millet. The effect of penoxsulam on the chlorophyll metabolism pathway of foxtail millet and its physiological mechanism was studied. Spraying penoxsulam on foxtail millet leaves significantly reduced the content of chlorophyll synthesis precursors (5-aminolevulinic acid (ALA), Porphobilinogen (PBG), Protoporphyrin IX (ProtoIX), Mg-protoporphyrin IX (Mg-ProtoIX), and Protochlorophyllide (Pchlide)). Moreover, the activities of key synthetic enzymes (magnesium chelatase (MgCh) decreased compared to control, while the activities of degrading enzymes (pheophorbide a oxygenase (PAO) and pheophytinase activities (PPH) increased significantly. The study revealed the mechanism of penoxsulam inducing crop phytotoxicity by interfering with the dynamic balance of chlorophyll metabolism, which provided a theoretical basis for the scientific application of herbicides and the study of foxtail millet drug resistance. Full article

In metabolically engineered plants, the target products are usually uniformly distributed in the whole plant or specific tissues. When engineering tobacco to produce astaxanthin, a ketocarotenoid with strong antioxidant activity and multiple bioactivities, a scattered distribution of astaxanthin-producing regions was observed in a small portion of astaxanthin-producing tobacco plants, which caused mosaic-like red and green spots on the leaves (ASTA-mosaic). A physiological assay showed that the non-astaxanthin green region (Mosaic_G) had relatively higher chlorophyll content and better chloroplast structure than the astaxanthin-producing red region (Mosaic_R). Then, metabolomics, proteomics, and small RNA transcriptomics were employed to analyze the uneven distribution of astaxanthin-producing regions in tobacco leaves. The results of metabolomics and proteomics revealed a decrease in carotenoid metabolism, chlorophyll biosynthesis, and chlorophyll degradation in the Mosaic_G region. Pheophorbide a, an intermediate of chlorophyll degradation, was found to be significantly reduced in the Mosaic_G region, which was accompanied by the attenuation of chlorophyllase and pheophytinase, which catalyze the formation of pheophorbide a in chlorophyll degradation. Reductions in photosynthetic antenna proteins and photosystem-associated proteins were observed in the Mosaic_R region, consistent with the better chloroplast structure of the Mosaic_G region. Small RNA transcriptomics showed that several small RNAs could target chlorophyll-degradative genes, but they were more effective in targeting the astaxanthin biosynthetic genes. This finding was supported by the fact that the Mosaic_G region can remain green up to the senescence of tobacco leaves. This work provides insights into the mechanism of the uneven distribution of astaxanthin-producing regions in tobacco leaves and may contribute to the specialized utilization of tobacco plants for metabolic engineering. Full article

The photoreduction of plastoquinone, a para-benzoquinone, by chlorophyll initiates photosynthesis in chloroplasts. The direct photoreduction of biologically relevant quinones by dietary chlorophyll metabolites has been reported and may influence health outcomes. We examined red light-mediated photoreduction of ortho- and para-naphthoquinones including vitamin K₃ using the photosensitizers methylene blue and pheophorbide A, a chlorophyll metabolite. Naphthoquinone reduction was monitored by UV/Visible spectroscopy and required a photosensitizer, red light and a tertiary amine electron donor. Combinations of methylene blue and ethylenediaminetetraacetic acid or pheophorbide A and triethanolamine in 20% dimethylformamide were employed for all photoreduction experiments. Hydrogen peroxide was generated during the photochemical reactions by singlet oxygen-dependent oxidation of the reduced naphthoquinones. Hydrogen peroxide was quantified with horseradish peroxidase following irradiation; the reduced naphthoquinones acted as peroxidase co-substrates. Histidine, a singlet oxygen scavenger, enhanced the rate of photoreduction by limiting the re-oxidation process. Catalase slowed the rate of photoreduction by regenerating molecular oxygen from hydrogen peroxide so that it could be photoexcited to singlet oxygen. The rates and extent of naphthoquinone photoreduction were dependent on molecular oxygen exposure in different reaction formats including in a cuvette and a plate well. Reduction of the tetrazolium salt MTT to the formazan via electron transfer from the photoreduced quinones was also used to quantitate the extent of photoreduction. Full article

Dengue fever is a mosquito-borne viral infection that recently appeared in Upper Egypt. Globally, more than 50 million new infections occur annually. It currently lacks effective treatment, necessitating vector control strategies targeting Aedes aegypti. This study investigates the potential of chlorophyllin as a control agent against dengue vectors. Chlorophyllin was characterized by FTIR analysis. The singlet oxygen quantum yield was determined by comparing the luminescence intensity at 1270 nm with that of phenalenone, yielding a value of 0.18. LC₅₀ and LC₉₀ values were calculated for chlorophyllin. Its larvicidal efficacy was assessed, revealing an LC₅₀ of 0.47 ppm in controlled laboratories and 93.3 ppm in semi-field conditions, demonstrating its superior potency against Aedes aegypti compared to pheophorbide and Bacillus sphaericus. Genotoxicity was analyzed through Random Amplified Polymorphic DNA (RAPD)-PCR, and histopathological changes were documented through microscopic examination. The genotoxicity results revealed high similarity in the DNA configurations of chlorophyllin-treated larvae and healthy individuals (similarity index of 0.8), whereas pheophorbide and Bacillus sphaericus exhibited substantial genetic deviations. Histopathological analysis demonstrated severe disruptions in chlorophyllin-treated larvae’s gut epithelial cells and muscle tissues, including epithelial detachment and irregular cell shapes. These findings position chlorophyllin as a promising gut toxin larvicide for Aedes aegypti control, with a more favorable genetic safety profile than conventional chemicals. Full article

The extract of Scenedesmus deserticola JD052 has been reported to exhibit anti-aging effects on the skin, with research indicating an increase in loliolide, a major active component, through heterotrophic cultivation. In this study, we evaluated the effects of extracts obtained from both photoautotrophic (PE) and heterotrophic (HE) cultures on hair-inductive properties in human dermal papilla (HDP) cells. Biochemical assays demonstrated that both extracts enhanced HDP cell viability and increased the size of three-dimensional dermal papilla (DP) spheres. Notably, the activation of β-catenin, a crucial marker associated with hair growth, was assessed using a luciferase reporter assay, revealing that HE exhibited a significantly higher efficacy than PE. Further analyses indicated that HE promoted the translocation of β-catenin into the nucleus through the phosphorylation and activation of AKT, which also elevated the expression levels of DP signature genes and hair-growth-related autocrine factors. Additionally, conditioned media from HE-treated HDP cells enhanced keratinocyte migration and increased the expression of growth factors, including VEGF and IGF-1. HPLC-MS analysis showed no significant difference in loliolide content; however, specific peaks in HE were identified as pheophorbide A and linolelaidic acid. Thus, HE may enhance hair growth inductivity via AKT/β-catenin signaling. Full article

Arsenic is a common toxic heavy metal contaminant that is widely present in the ocean, and seaweeds have a strong ability to concentrate arsenic, posing a potential risk to human health. This study first analyzed the arsenic content in two different seaweeds and then used an innovative method to categorize the seaweeds into low-arsenic and high-arsenic groups based on their arsenic exposure levels. Finally, a non-targeted metabolomic analysis based on mass spectrometry was conducted on seaweed from different arsenic exposure groups. The results indicated that as the arsenic concentration increased in the seaweeds, linolenic acid, tyrosine, pheophorbide a, riboflavin, and phenylalanine were upregulated, while arachidonic acid, eicosapentaenoic acid (EPA), betaine, and oleamide were downregulated. The following four key metabolic pathways involving unsaturated fatty acids and amino acids were identified: isoquinoline alkaloid biosynthesis, tyrosine metabolism, phenylalanine metabolism, and riboflavin metabolism. The identification of biomarkers and the characterization of key metabolic pathways will aid in the selection and breeding of low-arsenic-accumulating seaweed varieties, providing insights into the metabolic and detoxification mechanisms of arsenic in seaweeds. Full article