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1.
Allergol Immunopathol (Madr) ; 52(4): 91-96, 2024.
Article in English | MEDLINE | ID: mdl-38970271

ABSTRACT

Asthma is a widely prevalent chronic disease that brings great suffering to patients and may result in death if it turns severe. Jolkinolide B (JB) is one diterpenoid component separated from the dried roots of Euphorbia fischeriana Steud (Euphorbiaceae), and has anti--inflammatory, antioxidative, and antitumor properties. However, the detailed regulatory role and associated regulatory mechanism in the progression of asthma remain elusive. In this work, it was demonstrated that the extensive infiltration of bronchial inflammatory cells and the thickening of airway wall were observed in ovalbumin (OVA)-induced mice, but these impacts were reversed by JB (10 mg/kg) treatment, indicating that JB relieved the provocative symptoms in OVA-induced asthma mice. In addition, JB can control OVA-triggered lung function and pulmonary resistance. Moreover, JB attenuated OVA-evoked inflammation by lowering the levels of interleukin (IL)-4, IL-5, and IL-13. Besides, the activated nuclear factor kappa B (NF-κB) and transforming growth factor-beta-mothers against decapentaplegic homolog 3 (TGFß/smad3) pathways in OVA-induced mice are rescued by JB treatment. In conclusion, it was disclosed that JB reduced allergic airway inflammation and airway remodeling in asthmatic mice by modulating the NF-κB and TGFß/smad3 pathways. This work could offer new opinions on JB for lessening progression of asthma.


Subject(s)
Airway Remodeling , Asthma , Disease Models, Animal , Diterpenes , Mice, Inbred BALB C , NF-kappa B , Ovalbumin , Animals , Asthma/drug therapy , Asthma/immunology , Airway Remodeling/drug effects , Mice , Diterpenes/pharmacology , Diterpenes/administration & dosage , Diterpenes/therapeutic use , Ovalbumin/immunology , NF-kappa B/metabolism , Female , Transforming Growth Factor beta/metabolism , Cytokines/metabolism , Smad3 Protein/metabolism , Signal Transduction/drug effects , Humans , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Anti-Asthmatic Agents/pharmacology , Anti-Asthmatic Agents/therapeutic use , Euphorbia/chemistry
2.
Sci Rep ; 14(1): 15352, 2024 07 04.
Article in English | MEDLINE | ID: mdl-38961172

ABSTRACT

The genus Euphorbia (Euphorbiaceae) has near-cosmopolitan distribution and serves as a significant resource for both ornamental and medicinal purposes. Despite its economic importance, Euphorbia's taxonomy has long been challenged by the intricate nature of morphological traits exhibiting high levels of convergence. While molecular markers are essential for phylogenetic studies, their availability for Euphorbia has been limited. To address this gap, we conducted comparative analyses focusing on the chloroplast (CP) genomes of nine Euphorbia species, incorporating three newly sequenced and annotated accessions. In addition, phylogenetic informativeness and nucleotide diversity were computed to identify candidate markers for phylogenetic analyses among closely related taxa in the genus. Our investigation revealed relatively conserved sizes and structures of CP genomes across the studied species, with notable interspecific variations observed primarily in non-coding regions and IR/SC borders. By leveraging phylogenetic informativeness and nucleotide diversity, we identified rpoB gene as the optimal candidate for species delimitation and shallow-level phylogenetic inference within the genus. Through this comprehensive analysis of CP genomes across multiple taxa, our study sheds light on the evolutionary dynamics and taxonomic intricacies of Euphorbia, offering valuable insights into its CP genome evolution and taxonomy.


Subject(s)
Euphorbia , Genome, Chloroplast , Phylogeny , Euphorbia/genetics , Euphorbia/classification , Genome, Chloroplast/genetics , Evolution, Molecular , Genetic Variation
3.
J Med Chem ; 67(14): 12055-12067, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38959380

ABSTRACT

PCSK9 has been recognized as an efficient target for hyperlipidemia and related cardiovascular/cerebrovascular diseases. However, PCSK9 inhibitors in the clinic are all biological products, and no small molecules are available yet. In the current work, we discovered that the crude extract of Euphorbia esula (E. esula) promoted LDL uptake in vitro and then obtained 8 new and 12 known jatrophane diterpenoids by activity-guided isolation. After summarized their structure-activity relationship of PCSK9 inhibition, we selected compound 11 (C11) with potent activity and high abundance to investigate its mechanism and in vivo efficacy. Mechanistically, C11 bound with HNF1α to influence its nuclear distribution and subsequently inhibit PCSK9 transcription, thereby enhancing LDLR and promoting LDL uptake. Moreover, C11 demonstrated obvious lipid-lowering activity in HFD mouse model. In conclusion, we first revealed the novel application of E. esula in the discovery of a lipid-lowering candidate and highlighted the potential of C11 in the treatment of hyperlipidemia.


Subject(s)
Diterpenes , Euphorbia , Proprotein Convertase 9 , Euphorbia/chemistry , Diterpenes/pharmacology , Diterpenes/chemistry , Diterpenes/isolation & purification , Animals , Proprotein Convertase 9/metabolism , Proprotein Convertase 9/genetics , Humans , Mice , Structure-Activity Relationship , Male , Hyperlipidemias/drug therapy , Hyperlipidemias/metabolism , Hep G2 Cells , Mice, Inbred C57BL , Transcription, Genetic/drug effects , Lipid Metabolism/drug effects , PCSK9 Inhibitors
4.
Genes (Basel) ; 15(7)2024 Jul 21.
Article in English | MEDLINE | ID: mdl-39062736

ABSTRACT

The spurge Euphorbia characias is known for its latex, which is rich in antioxidant enzymes and anti-phytopathogen molecules. In this study, we identified a novel polyubiquitin protein in the latex and leaves, leading to the first molecular characterization of its coding gene and expressed protein in E. characias. Using consensus-degenerate hybrid oligonucleotide primers (CODEHOP) and rapid amplification of cDNA ends (5'/3'-RACE), we reconstructed the entire open reading frame (ORF) and noncoding regions. Our analysis revealed that the polyubiquitin gene encodes five tandemly repeated sequences, each coding for a ubiquitin monomer with amino acid variations in four of the five repeats. In silico studies have suggested functional differences among monomers. Gene expression peaked during the summer, correlating with high temperatures and suggesting a role in heat stress response. Western blotting confirmed the presence of polyubiquitin in the latex and leaf tissues, indicating active ubiquitination processes. These findings enhance our understanding of polyubiquitin's regulatory mechanisms and functions in E. characias, highlighting its unique structural and functional features.


Subject(s)
Euphorbia , Gene Expression Regulation, Plant , Plant Proteins , Polyubiquitin , Euphorbia/genetics , Polyubiquitin/genetics , Polyubiquitin/metabolism , Plant Proteins/genetics , Seasons , Latex/metabolism , Latex/chemistry , Plant Leaves/genetics , Plant Leaves/metabolism , Phylogeny
5.
Fitoterapia ; 177: 106111, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38971330

ABSTRACT

Euphorbia lathyris L. (EL) is a traditional poisonous herbal medicine used to treat dropsy, ascites, amenorrhea, anuria and constipation. Processing to reduce toxicity of EL is essential for its safe and effective application. However, there is little known regarding the molecular mechanism of reducing toxicity after EL processing. This research aimed to screen the differential markers for EL and PEL, explore the differential mechanisms of inflammatory injury induced by EL and processed EL (PEL) to expound the mechanism of alleviating toxicity after EL processing. The results showed that 15 potential biomarkers, mainly belonging to diterpenoids, were screened to distinguish EL from PEL. EL promoted the expressions of TLR4, NLRP3, NF-κB p65, IL-1ß and TNF-α, increased lipid rafts abundance and promoted TLR4 positioning to lipid rafts. Meanwhile, EL decreased LXRα and ABCA1 expression, and reduced cholesterol efflux. In contrast to EL, the effects of PEL on these indicators were markedly weakened. In addition, Euphorbia factors L1, L2, and L3 affected LXRα, ABCA1, TLR4, NLRP3, NF-κB p65, TNF-α and IL-1ß expression, influenced cholesterol efflux and lipid rafts abundance, and interfered with the colocalization of TLR4 and lipid rafts. The inflammatory injury caused by processed EL was significantly weaker than that caused by crude EL, and reduction of Euphorbia factors L1, L2, and L3 as well as attenuation of inflammatory injury participated in processing-based detoxification of EL. Our results provide valuable insights into the attenuated mechanism of EL processing and will guide future research on the processing mechanism of toxic traditional Chinese medicine.


Subject(s)
ATP Binding Cassette Transporter 1 , Euphorbia , Liver X Receptors , Membrane Microdomains , Toll-Like Receptor 4 , Euphorbia/chemistry , Toll-Like Receptor 4/metabolism , Liver X Receptors/metabolism , Membrane Microdomains/drug effects , Membrane Microdomains/metabolism , Animals , Mice , ATP Binding Cassette Transporter 1/metabolism , Inflammation/drug therapy , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , RAW 264.7 Cells , Humans
6.
BMC Complement Med Ther ; 24(1): 261, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987732

ABSTRACT

BACKGROUND: Colon cancer, a prominent contributor to global cancer-related deaths, prompts the need for innovative treatment strategies. Euphorbia resinifera O. Berg (E. resinifera) and Euphorbia officinarum subsp. echinus Hook. f. & Coss Vindt (E. echinus) and their bee-derived products have been integral to traditional Moroccan medicine due to their potential health benefits. These plants have historical use in addressing various health issues, including cancer. However, their effects against colon cancer remain unclear, and the specific mechanisms underlying their anti-cancer effects lack comprehensive investigation. METHODS: The study aimed to assess the potential anti-cancer effects of Euphorbia extract on colon cancer cell lines (DLD-1) through various techniques. The apoptosis, migration, and proliferation of DLD-1 cells were measured in DLD-1 cells. In addition, we conducted High-Performance Liquid Chromatography (HPLC) analysis to identify the profile of phenolic compounds present in the studied extracts. RESULTS: The extracts demonstrated inhibition of colon cancer cell migration. E. resinifera flower and E. echinus stem extracts show significant anti-migratory effects. Regarding anti-proliferative activity, E. resinifera flower extract hindered proliferation, whereas E. echinus flower extract exhibited dose-dependent inhibition. Apoptosis assays revealed E. resinifera flower extract inducing early-stage apoptosis and E. echinus flower extract promoting late-stage apoptosis. While apoptotic protein expression indicated, E. resinifera stem and propolis extracts had minimal impact on apoptosis. CONCLUSION: The findings provide evidence supporting the beneficial effects of E resinifera and E. echinus extracts on colon cancer and exerting anti-cancer properties.


Subject(s)
Apoptosis , Cell Proliferation , Colonic Neoplasms , Euphorbia , Plant Extracts , Euphorbia/chemistry , Humans , Colonic Neoplasms/drug therapy , Plant Extracts/pharmacology , Plant Extracts/chemistry , Cell Line, Tumor , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Movement/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Morocco
7.
Braz J Biol ; 84: e275974, 2024.
Article in English | MEDLINE | ID: mdl-39046047

ABSTRACT

The therapeutic potential of medicinal plants is known as an alternative in treatment of human affections; in effect, the conventional application of these medicinal sources has several limitations like low bioavailability, solubility and stability, which affect its pharmacological efficacy. In recent decades, extraordinary advances have been made in new drug delivery systems using nanocarriers. This work consisted in determining the in vitro antifungal activity of the methanolic extract of Euphorbia tirucalli formulated in polymeric nanoparticles. The antifungal activity was determined by the microdilution method in 96-well microplates, applying nanoparticles loaded with plant extract (NP-Ext) obtained by nanoprecipitation on clinical isolates of Trichophyton rubrum and T. interdigitalis. Regarding the nanoparticles, the lots used did not present significant differences in their physicochemical characteristics, with a size of 91.885 ± 1.621nm, polydispersity index of 0.152 ± 0.025 and Z-potential of -6.047 ± 0.987. The quantification of the extract in the polymeric matrix was determined by infrared spectroscopy (FTIR), where an efficiency and encapsulation percentage of 22.15 ± 0.82 and 2.95 ± 0.11, respectively, were obtained. The in vitro antifungal activity of the crude and formulated extract was obtained calculating the Minimum Inhibitory Concentration (MIC) of each one; a MIC of 125 µg/mL was obtained against T. rubrum and T. interdigitalis with the crude extract, while a MIC value of 55.55 and 0.1 µg/mL was obtained with NP-Ext, respectively, against these same. Conclusions: biological activity is closely linked to the phytochemical profile of the extract; while the improvement of said potential with the NP-Ext with the dosage form was directly related to the physicochemical characteristics of the nanocarrier.


Subject(s)
Antifungal Agents , Euphorbia , Microbial Sensitivity Tests , Nanoparticles , Plant Extracts , Euphorbia/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Nanoparticles/chemistry , Spectroscopy, Fourier Transform Infrared , Trichophyton/drug effects , Polymers/pharmacology , Polymers/chemistry , Arthrodermataceae
8.
Int Immunopharmacol ; 138: 112598, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-38981223

ABSTRACT

Euphorbia L. is a traditionally used herb and contains many newly identified compounds with novel chemical structures. Euphorbia factor L2 (EFL2), a diterpenoid derived from Euphorbia seeds, is reported to alleviate acute lung injury and arthritis by exerting anti-inflammatory effects. In this study, we aimed to test the therapeutic benefit and mechanisms of EFL2 in NLRP3 inflammasome-mediated gouty models and identified the potential molecular mechanism. A cell-based system was used to test the specific inhibitory effect of EFL2 on NLRP3-related inflammation. The gouty arthritis model and an air pouch inflammation model induced by monosodium urate monohydrate (MSU) crystals were used for in vivo experiments. Nlrp3-/- mice and in vitro studies were used for mechanistic exploration. Virtual molecular docking and biophysical assays were performed to identify the direct binding and regulatory target of EFL2. The inhibitory effect of EFL2 on inflammatory cell infiltration was determined by flow cytometry in vivo. The mechanism by which EFL2 activates the NLRP3 inflammasome signaling pathway was evaluated by immunological experiment and transmission electron microscopy. In vitro, EFL2 specifically reduced NLRP3 inflammasome-mediated IL-1ß production and alleviated MSU crystal-induced arthritis, as well as inflammatory cell infiltration. EFL2 downregulated NF-κB phosphorylation and NLRP3 inflammasome expression by binding to glucocorticoid receptors. Moreover, EFL2 could specifically suppress the lysosome damage-mediated NLRP3 inflammasome activation process. It is expected that this work may be useful to accelerate the development of anti-inflammatory drugs originated from traditional herbs and improve therapeutics in gout and its complications.


Subject(s)
Anti-Inflammatory Agents , Euphorbia , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Animals , Humans , Male , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Arthritis, Gouty/drug therapy , Arthritis, Gouty/immunology , Arthritis, Gouty/metabolism , Arthritis, Gouty/chemically induced , Disease Models, Animal , Diterpenes/pharmacology , Diterpenes/therapeutic use , Euphorbia/chemistry , Gout/drug therapy , Gout/immunology , Gout/pathology , Inflammasomes/metabolism , Interleukin-1beta/metabolism , Mice, Inbred C57BL , Mice, Knockout , Molecular Docking Simulation , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Signal Transduction/drug effects , Uric Acid
9.
Eur J Pharm Biopharm ; 201: 114353, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38885911

ABSTRACT

The latent reservoir of human immunodeficiency virus (HIV) is a major obstacle in the treatment of acquired immune deficiency syndrome (AIDS). The "shock and kill" strategy has emerged as a promising approach for clearing HIV latent reservoirs. However, current latency-reversing agents (LRAs) have limitations in effectively and safely activating the latent virus and reducing the HIV latent reservoirs in clinical practice. Previously, EK-16A was extracted from Euphorbia kansui, which had the effect of interfering with the HIV-1 latent reservoir and inhibiting HIV-1 entry. Nevertheless, there is no suitable and efficient EK-16A oral formulation for in vivo delivery and clinical use. In this study, an oral EK-16A self-nanoemulsifying drug delivery system (EK-16A-SNEDDS) was proposed to "shock" the HIV-1 latent reservoir. This system aims to enhance the bioavailability and delivery of EK-16A to various organs. The composition of EK-16A-SNEDDS was optimized through self-emulsifying grading and ternary phase diagram tests. Cell models, pharmacokinetic experiments, and pharmacodynamics in HIV-1 latent cell transplant animal models suggested that EK-16A-SNEDDS could be absorbed by the gastrointestinal tract and enter the blood circulation after oral administration, thereby reaching various organs to activate latent HIV-1. The prepared EK-16A-SNEDDS demonstrated safety and efficacy, exhibited high clinical experimental potential, and may be a promising oral preparation for eliminating HIV-1 latent reservoirs.


Subject(s)
Emulsions , HIV-1 , Virus Latency , HIV-1/drug effects , Virus Latency/drug effects , Animals , Administration, Oral , Humans , Virus Activation/drug effects , Euphorbia/chemistry , HIV Infections/drug therapy , HIV Infections/virology , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Biological Availability , Nanoparticle Drug Delivery System , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/pharmacology , Anti-HIV Agents/pharmacokinetics , Male , Drug Delivery Systems/methods , Mice
10.
Phytochemistry ; 225: 114193, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38908463

ABSTRACT

Lathyrisone A (1), a diterpene with an undescribed tricyclic 6/6/6 fused carbon skeleton, along with spirolathyrisins B-D (3-5), three diterpenes with a rare [4.5.0] spirocyclic carbon skeleton, and one known compound (2) were isolated from the roots of Euphorbia lathyris. Their chemical structures were characterized by extensive spectroscopic analysis, X-ray crystallography, ECD and quantum chemistry calculation. A plausible biosynthetic pathway for compounds 1-5 was proposed, which suggested it is a competitive pathway for ingenol biosynthesis in the plant. The anti-fungal activities of these compounds were tested, especially, compound 2 showed stronger anti-fungal activities against Fusarium oxysporum and Alternaria alternata than the positive control fungicide thiophanate-methyl. The preliminary structure-activity relationship of compounds 1-5 was also discussed. These results not only expanded the chemical diversities of E. lathyris, but also provided a lead compound for the control of plant pathogens.


Subject(s)
Alternaria , Antifungal Agents , Diterpenes , Euphorbia , Fusarium , Microbial Sensitivity Tests , Plant Roots , Euphorbia/chemistry , Diterpenes/chemistry , Diterpenes/pharmacology , Diterpenes/isolation & purification , Plant Roots/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Structure-Activity Relationship , Fusarium/drug effects , Alternaria/drug effects , Molecular Structure , Drug Discovery , Crystallography, X-Ray , Dose-Response Relationship, Drug
11.
Sci Data ; 11(1): 658, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38906925

ABSTRACT

Euphorbia, one of the largest genera of flowering plants, is well-known for containing many biofuel crops. Euphorbia tirucalli, an evergreen succulent mainly native to the Africa continent but cultivated worldwide, is a promising petroleum plant with high tolerance to drought and salt stress. However, the exploration of such an important plant resource is severely hampered by the lack of a reference genome. Here, we present the chromosome-level genome assembly of E. tirucalli using PacBio HiFi sequencing and Hi-C technology. Its genome size was approximately 745.62 Mb, with a contig N50 of 74.16 Mb. A total of 743.63 Mb (99.73%) of the assembled sequences were anchored to 10 chromosomes with a complete BUSCO score of 97.80%. Genome annotation revealed 26,304 protein-coding genes, and 76.37% of the genome was identified as repeat elements. The high-quality genome provides valuable genetic resources that would be useful for unraveling the genetic mechanisms of biofuel synthesis and evolutionary adaptation of E. tirucalli.


Subject(s)
Euphorbia , Genome, Plant , Euphorbia/genetics , Chromosomes, Plant , Stress, Physiological , Molecular Sequence Annotation
12.
J Nat Prod ; 87(6): 1574-1581, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38789921

ABSTRACT

Natural products represent a rich source of bioactive compounds, covering a large chemical space. Even if challenging, this diversity can be extended by applying chemical modifications. However, these studies generally require multigram amounts of isolated natural products and face frequent testing failures. To overcome this limitation, we propose a rapid and efficient approach that uses molecular networking (MN) to visualize the new chemical diversity generated by simple chemical modifications of natural extracts. Moreover, the strategy deployed enables the most appropriate reagents to be defined quickly upstream of a reaction on a pure compound, in order to maximize chemical diversity. This methodology was applied to the latex extract of Euphorbia dendroides to follow the reactivity toward a series of Brønsted and Lewis acids of three class of diterpene esters identified in this species: jatrophane, terracinolide, and phorbol. Through the molecular networking interpretation, with the aim to illustrate our approach, BF3·OEt2 was selected for chemical modification on isolated jatrophane esters. Three rearranged compounds (3-5) were obtained, showing that the most appropriate reagents can be selected by MN interpretation.


Subject(s)
Biological Products , Diterpenes , Esters , Euphorbia , Plant Extracts , Euphorbia/chemistry , Diterpenes/chemistry , Diterpenes/isolation & purification , Biological Products/chemistry , Plant Extracts/chemistry , Esters/chemistry , Molecular Structure
13.
Am J Bot ; 111(5): e16327, 2024 05.
Article in English | MEDLINE | ID: mdl-38725176

ABSTRACT

PREMISE: Quaternary climatic fluctuations and long-distance seed dispersal across the sea are critical factors affecting the distribution of coastal plants, but the spatiotemporal nature of population expansion and distribution change of East Asian coastal plants during this period are rarely examined. To explore this process, we investigated the genome-wide phylogenetic patterns of Euphorbia jolkinii Boiss. (Euphorbiaceae), which grows widely on littoral areas of Japan, Korea, and Taiwan. METHODS: We used plastome sequences and genome-wide single nucleotide polymorphisms in samples across the species range to reveal phylogeographic patterns and spatiotemporal distributional changes. We conducted ecological niche modeling for the present and the last glacial maximum (LGM). RESULTS: Genetic differentiation was observed between the northern and southern populations of E. jolkinii, separated by the major biogeographic boundary, the Tokara Gap. These two groups of populations differentiated during the glacial period and subsequently intermingled in the intermorainic areas of the central Ryukyu Islands after the LGM. Ecological niche models suggested that the potential range of E. jolkinii was restricted to southern Kyushu; however, it was widespread in the southern Ryukyu Islands and Taiwan during the LGM. CONCLUSIONS: This study provides evidence of genetic differentiation among coastal plant populations separated by the prominent biogeographical boundary. Although coastal plants are typically expected to maintain population connectivity through sea-drifted seed dispersal, our findings suggest that genetic differences may arise because of a combination of limited gene flow and changes in climate during the glacial period.


Subject(s)
Euphorbia , Phylogeography , Euphorbia/genetics , Euphorbia/physiology , Asia, Eastern , Phylogeny , Polymorphism, Single Nucleotide , Genetic Variation , Ecosystem
14.
J Asian Nat Prod Res ; 26(8): 900-909, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38753580

ABSTRACT

Nine jatrophane diterpenoids were isolated from the whole plant Euphorbia helioscopia, including two new ones, helioscopnins A (1) and B (2). Comprehensive spectroscopic data analysis and ECD calculations elucidated their structures, including absolute configurations. All compounds were evaluated for bioactivity towards autophagic flux by flow cytometry using HM mCherry-GFP-LC3 cells. Compounds 1, 3, 4, 5, 8, and 9 significantly increased autophagic flux.


Subject(s)
Autophagy , Diterpenes , Euphorbia , Euphorbia/chemistry , Diterpenes/pharmacology , Diterpenes/chemistry , Diterpenes/isolation & purification , Autophagy/drug effects , Molecular Structure , Humans
15.
Mol Plant ; 17(7): 1073-1089, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38807367

ABSTRACT

The gray mold fungus Botrytis cinerea is a necrotrophic pathogen that causes diseases in hundreds of plant species, including high-value crops. Its polyxenous nature and pathogenic success are due to its ability to perceive host signals in its favor. In this study, we found that laticifer cells of Euphorbia lathyris are a source of susceptibility factors required by B. cinerea to cause disease. Consequently, poor-in-latex (pil) mutants, which lack laticifer cells, show full resistance to this pathogen, whereas lot-of-latex mutants, which produce more laticifer cells, are hypersusceptible. These S factors are triterpenoid saponins, which are widely distributed natural products of vast structural diversity. The downregulation of laticifer-specific oxydosqualene cyclase genes, which encode the first committed step enzymes for triterpene and, therefore, saponin biosynthesis, conferred disease resistance to B. cinerea. Likewise, the Medicago truncatula lha-1 mutant, compromised in triterpenoid saponin biosynthesis, showed enhanced resistance. Interestingly, the application of different purified triterpenoid saponins pharmacologically complemented the disease-resistant phenotype of pil and hla-1 mutants and enhanced disease susceptibility in different plant species. We found that triterpenoid saponins function as plant cues that signal transcriptional reprogramming in B. cinerea, leading to a change in its growth habit and infection strategy, culminating in the abundant formation of infection cushions, the multicellular appressoria apparatus dedicated to plant penetration and biomass destruction in B. cinerea. Taken together, these results provide an explanation for how plant triterpenoid saponins function as disease susceptibility factors to promote B. cinerea pathogenicity.


Subject(s)
Botrytis , Plant Diseases , Saponins , Triterpenes , Botrytis/pathogenicity , Saponins/pharmacology , Saponins/metabolism , Plant Diseases/microbiology , Triterpenes/metabolism , Triterpenes/pharmacology , Euphorbia/microbiology , Euphorbia/metabolism , Disease Resistance/genetics , Medicago truncatula/microbiology , Medicago truncatula/metabolism , Medicago truncatula/genetics , Mutation , Gene Expression Regulation, Plant
16.
J Nat Prod ; 87(5): 1479-1486, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38728656

ABSTRACT

Bioinspired skeleton transformation of a tricyclic lathyrane-type Euphorbia diterpene was conducted to efficiently construct a tetracyclic tigliane diterpene on a gram scale via a key aldol condensation. The tigliane diterpene was then respectively converted into naturally rare ingenane and rhamnofolane diterpenes through a semipinacol rearrangement and a visible-light-promoted regioselective cyclopropane ring-opening reaction. This work provides a concise strategy for high-efficiency access to diverse polycyclic Euphorbia diterpene skeletons from abundant lathyrane-type natural products and paves the way for biological activity investigation of naturally rare molecules.


Subject(s)
Diterpenes , Euphorbia , Diterpenes/chemistry , Diterpenes/isolation & purification , Euphorbia/chemistry , Molecular Structure , Biomimetics , Biological Products/chemistry
17.
Artif Cells Nanomed Biotechnol ; 52(1): 261-269, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38696143

ABSTRACT

The widespread dissemination of bacterial resistance has led to great attention being paid to finding substitutes for traditionally used antibiotics. Plants are rich in various phytochemicals that could be used as antibacterial therapies. Here, we elucidate the phytochemical profile of Euphorbia canariensis ethanol extract (EMEE) and then elucidate the antibacterial potential of ECEE against Pseudomonas aeruginosa clinical isolates. ECEE showed minimum inhibitory concentrations ranging from 128 to 512 µg/mL. The impact of ECEE on the biofilm-forming ability of the tested isolates was elucidated using crystal violet assay and qRT-PCR to study its effect on the gene expression level. ECEE exhibited antibiofilm potential, which resulted in a downregulation of the expression of the biofilm genes (algD, pelF, and pslD) in 39.13% of the tested isolates. The antibacterial potential of ECEE was studied in vivo using a lung infection model in mice. A remarkable improvement was observed in the ECEE-treated group, as revealed by the histological and immunohistochemical studies. Also, ELISA showed a noticeable decrease in the oxidative stress markers (nitric oxide and malondialdehyde). The gene expression of the proinflammatory marker (interleukin-6) was downregulated, while the anti-inflammatory biomarker was upregulated (interleukin-10). Thus, clinical trials should be performed soon to explore the potential antibacterial activity of ECEE, which could help in our battle against resistant pathogenic bacteria.


Subject(s)
Anti-Bacterial Agents , Euphorbia , Plant Extracts , Pseudomonas aeruginosa , Respiratory Tract Infections , Pseudomonas aeruginosa/drug effects , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Euphorbia/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Respiratory Tract Infections/drug therapy , Animals , Mice , Oxidative Stress/drug effects , Bacterial Load/drug effects , Gene Expression Regulation, Bacterial/drug effects
18.
Fitoterapia ; 176: 105987, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38703916

ABSTRACT

In Brazil, latex from Euphorbia umbellata (African milk tree) has been increasingly used in folk medicine to treat several types of cancer, including melanoma. The effect of lyophilized latex (LL), its hydroethanolic extract (E80), triterpene (F-TRI)- and diterpene (F-DIT)-enriched fractions, along with six isolated phorbol esters from LL and phorbol 12-myristate 13-acetate (PMA) on J774A.1, THP-1, SK-MEL-28, and B16-F10 cell line viability were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The compounds were identified by 2D-NMR and HRESIMS. The effect of the LL, extract and fractions on cell viability was also assessed through a resazurin reduction assay. At 100 µg/ml, LL, and its fractions moderately inhibited J774A.1 (37.5-59.5%) and THP-1 (12.6-43.6%) metabolism. LL (IC50 70 µg/ml) and F-TRI (IC50 68 µg/ml) were barely more effective against B16-F10 cells, and only F-TRI exerted an inhibitory effect on SK-MEL-28 cells (IC50 66-75 µg/ml). The samples did not effectively inhibit THP-1 growth (IC50 69-87 µg/ml, assessed by MTT). B16-F10 was susceptible to PMA (IC50 53 µM) and two 12-phenylacetate esters (IC50 56-60 µM), while SK-MEL-28 growth was inhibited (IC50 58 µM) by one of these kinds of esters with an additional 4ß-deoxy structure. Synagrantol A (IC50 39 µM) was as effective as PMA (IC50 47 µM) in inhibiting J774A.1 growth in a dose-dependent manner. Furthermore, an in silico study with target receptors indicated a high interaction of the compounds with the PKC proteins. These results provide useful knowledge on the effect of tigliane-type diterpenes on tumor cell from the perspective of medicinal chemistry.


Subject(s)
Euphorbia , Latex , Phorbol Esters , Euphorbia/chemistry , Latex/chemistry , Phorbol Esters/pharmacology , Humans , Mice , Animals , Cell Line, Tumor , Molecular Structure , Plant Extracts/pharmacology , Plant Extracts/chemistry , Brazil , Monocytes/drug effects , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Cell Survival/drug effects , Diterpenes/pharmacology , Diterpenes/isolation & purification , Terpenes/pharmacology , Terpenes/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Tetradecanoylphorbol Acetate , Melanoma/drug therapy
19.
Fitoterapia ; 176: 106009, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38759735

ABSTRACT

Euphorbia himalayensis Boiss. is an alpine member of the Euphorbiaceae family. Its dried roots have been used to treat digestive problems and chest congestion in traditional Tibetan and Mongolian medicine. Despite thousands of years of use in medicine, the bioactive compounds of the root remain unknown. Herein, we isolated a novel aqueous-soluble polysaccharide (EHP2) from the E. himalayensis root and determined its structural characteristics via high-performance gel permeation chromatography, Fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectrometry. The homogeneous molecular weight of EHP2 was 23.6 kDa with narrow polydisperity (Mw/Mn = 1.4), and EHP2 mainly comprised of glucose (86.4%), galactose (11.9%) and mannose (1.7%). The major backbone of EHP2 was →4)-α-D-GalAp-(1 â†’ 4)-α-D-Glcp-(1 â†’ and the branch chain was α-D-Glcp-(1→. The antioxidant activity of the EHP2 was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion radical scavenging assays, and antioxidant enzyme activity (SOD, GSH and MDA) was determined in human umbilical vein endothelial cells (HUVECs). The EHP2 demonstrated lower potential scavenging effects on DPPH and superoxide free radical scavenger than ascorbic acid, and in HUVECs, it led to increased SOD and GSH activities and decreased MDA levels. This study is the first to describe an E. himalayensis polysaccharide compound with potential antioxidant activity.


Subject(s)
Antioxidants , Euphorbia , Human Umbilical Vein Endothelial Cells , Plant Roots , Polysaccharides , Euphorbia/chemistry , Antioxidants/pharmacology , Antioxidants/isolation & purification , Polysaccharides/pharmacology , Polysaccharides/isolation & purification , Polysaccharides/chemistry , Plant Roots/chemistry , Humans , Human Umbilical Vein Endothelial Cells/drug effects , Molecular Structure , Phytochemicals/pharmacology , Phytochemicals/isolation & purification
20.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2441-2450, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38812143

ABSTRACT

This study aims to explore the correlation between intestinal toxicity and composition changes of Euphorbia ebracteolata before and after Terminalia chebula soup(TCS) processing. Intragastric administration was performed on the whole animal model. By using fecal water content, inflammatory causes, and pathological damage of different parts of the intestinal tract of mice as indexes, the differences in intestinal toxicity of dichloromethane extraction of raw E. ebracteolata(REDE), dichloromethane extraction of TCS, and dichloromethane extraction of E. ebracteolata after simulated TCS processing(STREDE) were compared, so as to investigate the effect of TCS processing on the intestinal toxicity of E. ebracteolata. At the same time, the component databases of E. ebracteolata and T. chebula were constructed, and the composition changes of diterpenoids, tannins, and phenolic acids in the three extracted parts were analyzed by HPLC-TOF-MS. HPLC was used to compare the content of four diterpenoids including ent-11α-hydroxyabicta-8(14), 13(15)-dien-16, 12-olide(HAO), jolkinolide B(JNB), fischeria A(FA), and jolkinolide E(JNE) in the E. ebracteolata before and after processing and the residue of container wall after processing, so as to investigate the effect of TCS processing on the content and structure of the diterpenoids. The results showed that the REDE group could significantly increase the fecal water content and the release levels of TNF-α and IL-1ß from each intestinal segment, and intestinal tissue damage was accompanied by significant infiltration of inflammatory cells. However, compared with the REDE group, the intestinal tissue damage in the STREDE group was alleviated, and the infiltration of inflammatory cells decreased. The intestinal toxicity significantly decreased. Mass spectrometry analysis showed that there was no significant difference in the content of diterpenoids of REDE before and after simulated TCS processing, but a large number of tannins and phenolic acids were added. The results of HPLC showed that the content of four diterpenoids of E. ebracteo-lata decreased to varying degrees after TCS processing, ranging from-0.35% to-19.74%, and the decreased part mainly remained in the container wall, indicating that the structure of toxic diterpenoids of E. ebracteolata was not changed after TCS processing. The antagonistic effect of tannic and phenolic acids in the TCS may be the main reason for the reduced intestinal toxicity of E. ebracteolata after TCS processing. The TCS processing for E. ebracteolata is scientific.


Subject(s)
Drugs, Chinese Herbal , Euphorbia , Terminalia , Euphorbia/chemistry , Animals , Terminalia/chemistry , Mice , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/toxicity , Male , Intestines/drug effects , Intestines/chemistry , Chromatography, High Pressure Liquid , Humans
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