Biochemical characterization of Euphorbia resinifera floral cyathia.

Euphorbia resinifera O. Berg is a plant endemic to the Northern and Central regions of Morocco known since the ancient Roman and Greek times for secreting a poisonous latex containing resiniferatoxin. However, E. resinifera pseudo-inflorescences called cyathia are devoid of laticifers and, therefore, do not secrete latex. Instead, they exudate nectar that local honey bees collect and craft into honey. Honey and cyathium water extracts find a broad range of applications in the traditional medicine of Northern Africa as ointments and water decoctions. Moreover, E. resinifera monofloral honey has received the Protected Geographic Indication certification for its outstanding qualities. Given the relevance of E. resinifera cyathia for bee nutrition, honey production, and the health benefit of cyathium-derived products, this study aimed to screen metabolites synthesized and accumulated in its pseudo-inflorescences. Our analyses revealed that E. resinifera cyathia accumulate primary metabolites in considerable abundance, including hexoses, amino acids and vitamins that honey bees may collect from nectar and craft into honey. Cyathia also synthesize volatile organic compounds of the class of benzenoids and terpenes, which are emitted by flowers pollinated by honey bees and bumblebees. Many specialized metabolites, including carotenoids, flavonoids, and polyamines, were also detected, which, while protecting the reproductive organs against abiotic stresses, also confer antioxidant properties to water decoctions. In conclusion, our analyses revealed that E. resinifera cyathia are a great source of antioxidant molecules and a good food source for the local foraging honeybees, revealing the central role of the flowers from this species in mediating interactions with local pollinators and the conferral of medicinal properties to plant extracts.

In vitro Adipocyte Differentiation Inhibition and in vivo Effects on Lipid Metabolism in High-Fat Diet-Induced Obesity of Euphorbia humifusa.

Euphorbia humifusa Willd (Euphorbiaceae) is a functional raw material with various pharmacological activities. This study aimed to validate the inhibitory effect of Euphorbia humifusa extract (EHE) on adipocyte differentiation in vitro and in a high-fat-diet (HFD)-induced mouse model to evaluate the E.a humifusa as a novel anti-obesity and lipid metabolism enhancer agent. EHE effects on obesity and lipid metabolism were assessed in HFD-induced obese mice after 4-week treatments. Results were compared among four treatment groups (n = 7/group): low fat diet (LFD), high fat diet (HFD), and HFD-induced obese mice treated with either 100 or 200 mg/kg/day EHE (EHE100 and EHE200, respectively). EHE (50 to 200 µg/ml) and quercetin (50 µg/ml) significantly reduced 3T3-L1 preadipocyte differentiation (p < 0.001), in a concentration-dependent manner. EHE affected lipid metabolism, as evidenced by changes in serum lipid components. The HFD-EHE100 and HFD-EHE200 groups exhibited significantly (p < 0.05) reduced triglycerides (TG, 97.50 ± 6.56 and 82.50 ± 13.20 mg/dL, respectively) and low-density lipoprotein-cholesterol (LDL-c: 40.25 ± 4.99 and 41.25 ± 6.36 mg/dL, respectively) compared to the HFD group (TG: 129.25 ± 19.81 mg/dL; LDL-c: 51.75 ± 11.59 mg/dL). Haematoxylin and Eosin (H&E) and Oil red O staining showed that EHE markedly reduced lipid accumulation and inhibited lipogenesis in the liver. Interestingly, EHE significantly (p < 0.01) reduced the expression of adipogenic transcription factors in liver tissue. Our results indicated that EHE has the potential to be a therapeutic agent for addressing obesity and lipid metabolism.

Lupenone, a wonder chemical obtained from Euphorbia segetalis to boost affinity for the transcriptional factor escalating drought-tolerance in Solanum Lycopersicum: A cutting-edge computational biology approach.

Drought is the single greatest abiotic factor influencing crop yield worldwide. Plants remain in one area for extended periods, making them vulnerable to natural and man-made influences. Understanding plant drought responses will help us develop strategies for breeding drought-resistant crops. Large proteome analysis revealed that leaf and root tissue proteins respond to drought differently depending on the plant's genotype. Commonly known as tomatoes, Solanum Lycopersicum is a globally important vegetable crop. However, drought stress is one of the most significant obstacles to tomato production, making the development of cultivars adapted to dry conditions an essential goal of agricultural biotechnology. Breeders have put quite a lot of time and effort into the tomato to increase its productivity, adaptability, and resistance to biotic and abiotic challenges. However, conventional tomato breeding has only improved drought resistance due to the complexity of drought traits. The resilience of tomatoes under drought stress has been the subject of extensive study. Using contemporary sequencing approaches like genomics, transcriptomics, proteomics, and metabolomics has dramatically aided in discovering drought-responsive genes. One of the most prominent families of plant transcription factors, WRKY genes, plays a crucial role in plant growth and development in response to natural and abiotic stimuli. To develop plants that can withstand both biotic and abiotic stress, understanding the relationships between WRKY-proteins (transcription factors) and other proteins and ligands in plant cells is essential. This is despite the fact that tomatoes have a long history of domestication. This research aims to utilize Lupenone, a hormone produced in plant roots in response to stress, to increase drought resistance in plants. Lupenone exhibits a strong affinity for the WRKY protein at -9.64 kcal/mol. Molecular docking and modeling studies show that these polyphenols have a significant role in making Solanum Lycopersicum drought-resistant and improving the quality of its fruit. As a result of climate change, droughts are occurring more frequently and persisting for more extended periods, making it necessary to breed crops resistant to drought. While considerable variability for tolerance exists in wild cousins, little is known about the processes and essential genes influencing drought tolerance in cultivated tomato species.

Effects of dietary Euphorbia heterophylla extract on the growth performance, physiological, antioxidative and immune responses of Clarias gariepinus juveniles.

Effects of dietary Euphorbia heterophylla extract (EH) on growth performance, feed utilization and haemato-biochemical parameters in African catfish, Clarias gariepinus, juveniles were evaluated in this study. Diets fortified with EH at 0 (control), 0.5, 1.0, 1.5 or 2.0 g/kg were fed to the fish to apparent satiation for 84 days before challenging it with Aeromonas hydrophila. The weight gain, specific growth rate and protein efficiency ratio of fish fed EH-supplemented diets were significantly higher but lower feed conversion ratio (p < 0.05) than the control group. The villi height and width at the proximal, mid and the distal of the guts rose significantly with the increasing levels of EH from 0.5 to 1.5 g than the fish fed basal diet. Dietary EH enhanced (p < 0.05) the packed cell volume and haemoglobin, whereas 1.5 g EH boosted white blood cell, in relation to their counterpart in the control group. There were significant increase in the activities of glutathione-S-transferase, glutathione peroxidase and superoxide dismutase (p < 0.05) in the fish that were fed diets supplemented with EH than the control. Dietary EH also enhanced phagocytic activities, lysozyme activities and relative survival (RS) of C. gariepinus than the control group, with the highest RS obtained in fish that were fed diet containing EH at 1.5 g/kg level. These results revealed that the fish fed 1.5 g/kg dietary EH promoted growth performance, antioxidant and immune profiles, as well as protection against A. hydrophila infection.

Cycloartane triterpenoid from Euphorbia macrostegia modulates ER stress signaling pathways to induce apoptosis in MDA-MB231 and MCF-7 breast cancer cell lines.

Unfolded protein response (UPR) is involved in breast cancer (BC) progression and drug resistance. Many natural products (NPs) could modulate UPR and used for therapeutic purposes. Herein, we aimed to investigate the molecular mechanism of Cycloart-23E-ene-3ß, 25-diol (Cycloart-E25), cytotoxicity, as a NP extracted from Euphorbia macrostegia and focused on endoplasmic-reticulum stress (ERS) and UPR signaling pathways. Reactive oxygen species (ROS) were probed by DCFDA fluorescence dye. Apoptosis was assayed by annexin V/propidium iodide (PI), immunoblotting of anti- and proapoptotic, Bcl-2 and Bax proteins, and mitochondrial transmembrane potential (ΔΨm) changes. Thioflavin T (ThT) staining and immunoblotting of UPR signaling components (CHOP, PERK, ATF6, BiP, and XBP1) were recruited for the assessment of ERS. Our results indicated that Cycloart-E25 noticeably increases ROS levels in both MB-231 MDA-MB-231 and MCF-7 cell lines, p>0.05. Flow cytometry assessments revealed an increase in the cell population undergoing apoptosis. Also, the Bax/Bcl-2 ratio increased in a dose-dependent manner following Cycloart-E25 treatment, significantly, p>0.05. Mitochondrial involvement could be deduced by significant decreases in ΔΨm, p>0.05. Cycloart-E25 potently induces protein aggregation and upregulated CHOP, PERK, ATF6, BiP, and XBP1 factors in both MDA-MB-231 MB-231 and MCF-7 cell lines, indicating the involvement of ERS in Cycloart-E25-mediated apoptosis. In conclusion, Cycloart-E25 increased the accumulation of misfolded proteins and upregulated UPR components. Therefore, induction of ERS may be involved in the trigger of apoptosis in BC cell lines. Cycloart-E25 induced apoptosis in breast cancer cell lines through ERS. More assessments are needed to confirm its in vivo anti-tumoral effects.

Microbial and chemical transformations of euphorbia factor L1 and the P-glycoprotein inhibitory activity in zebrafishes.

Euphorbia factor L1 (EFL1, 1) is a natural tri-ester of 6,17-epoxylathyrol with cancer multidrug resistance (MDR) reversal activity. Several EFL1 derivatives (2-9) were prepared by chemical and microbial transformations and their ability to inhibit P-glycoprotein (P-gp) activity was estimated. Six de-acylated derivatives (2-7) were obtained through base-hydrolysis of 1, and the base-catalysed hydrolysis via KOH and NaOH yielded different hydrolysed products of 1. Two biotransformed products (8-9) were directly obtained via microbial transformation of 1, and 8 was also formed by microbial conversion of the hydrolysed product 3. The P-gp modulation of 1-9 was assessed by a zebrafish model. The substrate 1 and its biotransformed product 9 as the tri-esters of lathyranes possessed the highest P-gp inhibitory activity with IC50 values of 34.97 and 15.50 µM, respectively, through down-regulating P-gp expression at the protein level rather than at MDR1 mRNA level.

An epigenetic modifier enhances the generation of anti-phytopathogenic compounds from the endophytic fungus Chaetomium globosporum of Euphorbia humifusa.

Endophytic fungi are striking resources rich in bioactive structures with agrochemical significance. In order to maximize the opportunity of search for bioactive compounds, chemical epigenetic manipulation was introduced to enhance the structural diversity of the fungal products, and an UPLC-ESIMS and bioassay-guided separation was used to detect novel bioactive metabolites. Consequently, four previously undescribed compounds including two cyclopentenones (globosporins A and B) and two monoterpenoid indole alkaloids (globosporines C and D), as well as three known compounds, were isolated from the endophytic fungus Chaetomium globosporum of Euphorbia humifusa by exposure to a DNA methyltransferase inhibitor 5-azacytidine. Their structures including the absolute configurations were elucidated by the analysis of NMR spectroscopic data, HRESIMS, and TD-DFT-ECD calculations. The indole alkaloids (globosporines C and D) showed antimicrobial activities against three phytopathogenic microbes (Xanthomonas oryzae pv. oryzae, X. oryzae pv. oryzicola, and Pseudomonas syringae pv. lachrymans) with MICs in the range of 14-72 µg/mL. Mostly, globosporine D was proved to be potently anti-phytopathogenic against X. oryzae pv. oryzae in vitro and in vivo, which suggested that it has the potential to be developed as a candidate for the prevention of rice bacterial leaf blight. This work provides an efficient and environmentally friendly approach for expanding fungal products with agricultural importance.

Identifying Terpenoid Biosynthesis Genes in Euphorbia maculata via Full-Length cDNA Sequencing.

The annual herb Euphorbia maculata L. produces anti-inflammatory and biologically active substances such as triterpenoids, tannins, and polyphenols, and it is used in traditional Chinese medicine. Of these bioactive compounds, terpenoids, also called isoprenoids, are major secondary metabolites in E. maculata. Full-length cDNA sequencing was carried out to characterize the transcripts of terpenoid biosynthesis reference genes and determine the copy numbers of their isoforms using PacBio SMRT sequencing technology. The Illumina short-read sequencing platform was also employed to identify differentially expressed genes (DEGs) in the secondary metabolite pathways from leaves, roots, and stems. PacBio generated 62 million polymerase reads, resulting in 81,433 high-quality reads. From these high-quality reads, we reconstructed a genome of 20,722 genes, in which 20,246 genes (97.8%) did not have paralogs. About 33% of the identified genes had two or more isoforms. DEG analysis revealed that the expression level differed among gene paralogs in the leaf, stem, and root. Whole sets of paralogs and isoforms were identified in the mevalonic acid (MVA), methylerythritol phosphate (MEP), and terpenoid biosynthesis pathways in the E. maculata L. The nucleotide information will be useful for identifying orthologous genes in other terpenoid-producing medicinal plants.

Conducting the RBD of SARS-CoV-2 Omicron Variant with Phytoconstituents from Euphorbia dendroides to Repudiate the Binding of Spike Glycoprotein Using Computational Molecular Search and Simulation Approach.

(1) Background: Natural constituents are still a preferred route for counteracting the outbreak of COVID-19. Essentially, flavonoids have been found to be among the most promising molecules identified as coronavirus inhibitors. Recently, a new SARS-CoV-2 B.1.1.529 variant has spread in many countries, which has raised awareness of the role of natural constituents in attempts to contribute to therapeutic protocols. (2) Methods: Using various chromatographic techniques, triterpenes (1-7), phenolics (8-11), and flavonoids (12-17) were isolated from Euphorbia dendroides and computationally screened against the receptor-binding domain (RBD) of the SARS-CoV-2 Omicron variant. As a first step, molecular docking calculations were performed for all investigated compounds. Promising compounds were subjected to molecular dynamics simulations (MD) for 200 ns, in addition to molecular mechanics Poisson-Boltzmann surface area calculations (MM/PBSA) to determine binding energy. (3) Results: MM/PBSA binding energy calculations showed that compound 14 (quercetin-3-O-ß-D-glucuronopyranoside) and compound 15 (quercetin-3-O-glucuronide 6″-O-methyl ester) exhibited strong inhibition of Omicron, with ΔGbinding of -41.0 and -32.4 kcal/mol, respectively. Finally, drug likeness evaluations based on Lipinski's rule of five also showed that the discovered compounds exhibited good oral bioavailability. (4) Conclusions: It is foreseeable that these results provide a novel intellectual contribution in light of the decreasing prevalence of SARS-CoV-2 B.1.1.529 and could be a good addition to the therapeutic protocol.

Gene discovery and virus-induced gene silencing reveal branched pathways to major classes of bioactive diterpenoids in Euphorbia peplus.

Most macro- and polycyclic Euphorbiaceae diterpenoids derive from the common C20 precursor casbene. While the biosynthetic pathway from casbene to the lathyrane jolkinol C is characterized, pathways to other more complex classes of bioactive diterpenoids remain to be elucidated. A metabolomics-guided transcriptomic approach and a genomics approach that led to the discovery of two casbene-derived diterpenoid gene clusters yielded a total of 68 candidate genes that were transiently expressed in Nicotiana benthamiana for activity toward jolkinol C and other lathyranes. We report two short-chain dehydrogenases/reductases (SDRs), identified by RNA sequencing to be highly expressed in Euphorbia peplus latex. One of these, EpSDR-5, is a C3-ketoreductase, converting jolkinol C to the lathyrane jolkinol E. Gene function of EpSDR-5 was further confirmed by heterologous expression in Saccharomyces cerevisiae. To investigate the in vivo role of EpSDR-5, we established virus-induced gene silencing (VIGS) in E. peplus, resulting in a significant reduction in jatrophanes and a corresponding increase in ingenanes. VIGS of Casbene Synthase results in a major reduction in both jatrophanes and ingenanes, the two most abundant classes of E. peplus diterpenoids. VIGS of CYP71D365 had a similar effect, consistent with the previously determined role of this gene in the pathway to jolkinol C. These results point to jolkinol C being a branch point intermediate in the pathways to ingenanes and jatrophanes with EpSDR-5 responsible for the first step from jolkinol C to jatrophane production.

Euphorbia factor L3 ameliorates rheumatoid arthritis by suppressing the inflammatory response by targeting Rac family small GTPase 1.

Euphorbia factor L3 (EFL3) is extracted from Euphorbia lathyris and is known for its anti-inflammatory properties. This study focused on the potential anti-inflammatory and therapeutic effects of EFL3 on rheumatoid arthritis (RA) using fibroblast-like synoviocytes (FLSs) and arthritis animal models. Functional analysis showed that EFL3 could ameliorate the inflammatory phenotype of FLSs derived from RA patients, as evidenced by the decreases in cell viability, migration, invasion and cytokine production. Luciferase activity, Western blotting and immunofluorescence assays demonstrated that EFL3 inhibited the nuclear translocation of the p65 subunit and the subsequent activation of the nuclear factor kappa-Β (NF-κB) pathway. Furthermore, the therapeutic effects of EFL3 against arthritic progression were evidenced by decreases in joint swelling, arthritis scores, inflammatory factor production, synovial hyperplasia, and bone destruction in collagen-induced arthritis (CIA) and tumor necrosis factor-α (TNF-α) transgenic (TNF-tg) mouse models. Molecular analysis identified Rac family small GTPase 1 (Rac1) as the potential target that was required for EFL3-mediated suppression of the inflammatory RA FLS phenotype. In summary, this study uncovered the therapeutic potential of EFL3 in RA, which suggests its future clinical use.

Computer-Guided Trypanocidal Activity of Natural Lactones Produced by Endophytic Fungus of Euphorbia umbellata.

Hundreds of millions of people worldwide are affected by Chagas' disease caused by Trypanosoma cruzi. Since the current treatment lack efficacy, specificity, and suffers from several side-effects, novel therapeutics are mandatory. Natural products from endophytic fungi have been useful sources of lead compounds. In this study, three lactones isolated from an endophytic strain culture were in silico evaluated for rational guidance of their bioassay screening. All lactones displayed in vitro activity against T. cruzi epimastigote and trypomastigote forms. Notably, the IC50 values of (+)-phomolactone were lower than benznidazole (0.86 vs. 30.78 µM against epimastigotes and 0.41 vs. 4.88 µM against trypomastigotes). Target-based studies suggested that lactones displayed their trypanocidal activities due to T. cruzi glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH) inhibition, and the binding free energy for all three TcGAPDH-lactone complexes suggested that (+)-phomolactone has a lower score value (-3.38), corroborating with IC50 assays. These results highlight the potential of these lactones for further anti-T. cruzi drug development.

A novel strategy of nanosized herbal Plectranthus amboinicus, Phyllanthus niruri and Euphorbia hirta treated TiO2 nanoparticles for antibacterial and anticancer activities.

Titanium dioxide nanoparticles exhibit good anticancer and antibacterial activities. They are known to be environmentally friendly, stable, less toxic, and have excellent biocompatibility nature. Due to these properties, they are well suited for biological applications particularly in biomedical applications such as drug delivery and cancer therapy. In this research article, three medicinal herbs namely, Plectranthus amboinicus (Karpooravalli), Phyllanthus niruri (Keezhanelli), and Euphorbia hirta (Amman Pacharisi), were used to modify the surface of the TiO2 nanoparticles. The synthesized nanoparticles were subjected to various characterization techniques. The samples are then subjected to MTT assay to determine cell viability. KB oral cancer cells are used for the determination of the anticancer nature of the pure and bio modified nanoparticles. It is observed that Plectranthus amboinicus-Phyllanthus niruri modified TiO2 nanoparticles exhibit excellent anticancer activities among other bio modified and pure samples. The samples are then examined for antibacterial activities against three Gram-negative bacterial strains namely, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and two Gram-positive bacterial strains namely, Staphylococcus aureus and Streptococcus mutans, respectively. Among the modified and pure samples, Plectranthus amboinicus showed good antibacterial activity against Gram-positive and Gram-negative bacteria. In the Flow cytometry analysis, the generation of p53 protein expression from Plectranthus amboinicus-Phyllanthus niruri modified TiO2 nano herbal particles shows the anti-cancerous nature of the sample. Then to determine the toxic nature of the Plectranthus amboinicus-Phyllanthus niruri modified TiO2 nano herbal particles against normal cells, the NPs were subjected to MTT assay against normal L929 cells, and it was found to be safer and less toxic towards the normal cells.

Latex Metabolome of Euphorbia Species: Geographical and Inter-Species Variation and its Proposed Role in Plant Defense against Herbivores and Pathogens.

Based on the hypothesis that the variation of the metabolomes of latex is a response to selective pressure and should thus be affected differently from other organs, their variation could provide an insight into the defensive chemical selection of plants. Metabolic profiling was used to compare tissues of three Euphorbia species collected in diverse regions. The metabolic variation of latexes was much more limited than that of other organs. In all the species, the levels of polyisoprenes and terpenes were found to be much higher in latexes than in leaves and roots of the corresponding plants. Polyisoprenes were observed to physically delay the contact of pathogens with plant tissues and their growth. A secondary barrier composed of terpenes in latex and in particular, 24-methylenecycloartanol, exhibited antifungal activity. These results added to the well-known role of enzymes also present in latexes, show that these are part of a cooperative defense system comprising biochemical and physical elements.

Extracts of Euphorbia nivulia Buch.-Ham. showed both phytotoxic and insecticidal capacities against Lemna minor L. and Oxycarenus hyalinipennis Costa.

Many phytochemicals can affect the growth and development of plants and insects which can be used as biological control agents. In this study, different concentrations of crude, hexane, chloroform, butanol, and aqueous extracts of Euphorbia nivulia Buch.-Ham., an endemic plant of the Cholistan desert in South Punjab of Pakistan, were analysed for their chemical constituents. Their various concentrations were also tested for their phytotoxic and insecticidal potential against duckweed, Lemna minor L., and the dusky cotton bug, Oxycarenus hyalinipennis Costa. various polyphenols, i.e., quercetin, gallic acid, caffeic acid, syringic acid, coumaric acid, ferulic acid, and cinnamic acid were detected in different concentrations with different solvents during the phytochemical screening of E. nivulia. In the phytotoxicity test, except for 100 µg/mL of the butanol extract gave 4.5% growth regulation, no phytotoxic lethality could be found at 10 and 100 µg/mL of all the extracts. The highest concentration, 1000 µg/mL, of the chloroform, crude, and butanol extracts showed 100, 63.1, and 27.1% of growth inhibition in duckweed, respectively. In the insecticidal bioassay, the highest O. hyalinipennis mortalities (87 and 75%) were recorded at 15% concentration of the chloroform and butanol extracts of E. nivulia. In contrast, the lower concentrations of the E. nivulia extracts caused the lower mortalities. Altogether, these findings revealed that E. nivulia chloroform extracts showed significant phytotoxicity while all the extracts showed insecticidal potential. This potential can be, further, refined to be developed for bio-control agents.

Bioactive tigliane diterpenoids from the latex of Euphorbia fischeriana.

Latex is a type of sticky endogenous fluids derived from diverse plants including Euphorbia fischeriana, and is of great scientific and commercial values. In the current study, it was demonstrated that the latex extracted from E. fischeriana strongly respelled the growth of cotton bollworm, Helicoverpa armigera. Using spectroscopic methods, HPLC, and GC-MS analyses, six aliphatic tigliane diterpenoids were isolated from the latex of E. fischeriana, among which three compounds (2, 3, and 5) were new. Two major compounds (1 and 4) exhibited remarkable antifeedant activity against H. armigera, with EC50 values at 2.59 and 15.32 µg/cm2, respectively. In addition, the quantification analysis of diterpenoids in different organs indicated that 4 was the most abundant constituent and was highly accumulated in the latex. Collectively, the current study highlighted that the diterpenoids in latex of E. fischeriana had a considerable antifeedant function against H. armigera, which might be employed for the future development of natural insecticides for organic farming.

Nitrogen-containing naringenin derivatives for reversing multidrug resistance in cancer.

Naringenin (1), isolated from Euphorbia pedroi, was previously derivatized yielding compounds 2-13. In this study, aiming at expanding the pool of analogues of the flavanone core towards better multidrug resistance (MDR) reversal agents, alkylation reactions and chemical modification of the carbonyl moiety was performed (15-39). Compounds structures were assigned mainly by 1D and 2D NMR experiments. Compounds 1-39 were assessed as MDR reversers, in human ABCB1-transfected mouse T-lymphoma cells, overexpressing P-glycoprotein (P-gp). The results revealed that O-methylation at C-7, together with the introduction of nitrogen atoms and aromatic moieties at C-4 or C-4', significantly improved the activity, being compounds 27 and 37 the strongest P-gp modulators and much more active than verapamil. In combination assays, synergistic interactions of selected compounds with doxorubicin substantiated the results. While molecular docking suggested that flavanone derivatives act as competitive modulators, molecular dynamics showed that dimethylation promotes binding to a modulator-binding site. Moreover, flavanones may also interact with a vicinal ATP-binding site in both nucleotide-binding domains, hypothesizing an allosteric mode of action.

Modified green synthesis of Fe3O4@SiO2 nanoparticles for pH responsive drug release.

A magnetic field activated drug delivery and pH-sensitive controlled drug release system based on carboxyl-modified green synthesized Fe3O4@SiO2 (Fe3O4@SiO2-Glu) nanoparticles was established. Doxorubicin hydrochloride (DOX), as a drug model, was adsorbed onto the Fe3O4@SiO2-Glu nanoparticles' surface, where the observed drug loading capacity of 34.6 mg/g was attributed to electrostatic interaction between -COO- on the surface of Fe3O4@SiO2-Glu and -NH3+ of DOX. The structure, morphology and physiochemical properties of Fe3O4@SiO2-Glu were characterized via TEM, FTIR, XRD, N2 adsorption/desorption isotherms, and Zeta potential measurements. The green synthesized Fe3O4@SiO2-Glu nanoparticles exhibited multilayer architecture with a BET surface area of 79.9 m2/g and a magnetization saturation of 25.9 emu/g. Drug release experiments indicated that DOX was pH trigger released with 60.8% released within 72 h at pH 3.5. This system has important potential implications for the design of more effective and stable magnetic Fe3O4@SiO2-Glu materials as drug carriers for targeted and controlled drug release.

Gold nanoparticles synthesized from Euphorbia fischeriana root by green route method alleviates the isoprenaline hydrochloride induced myocardial infarction in rats.

The procurance of gold nanoparticles in the plant extracts is an excellent way to attain nanomaterials natural and eco-friendly nanomaterials. The Dehydrated roots of Chinese Euphorbia fischeriana flowering plant are called "Lang-Du". In this study, the retrieving of gold nanoparticles from Euphorbia fischeriana root was amalgamated by standard procedure. Fabricated gold nanoparticles were portrayed through the investigations of ultraviolet and visible spectrophotometry (UV-Vis), Fourier transform infrared spectroscopy (FTIR), High resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). The UV-Vis and FTIR results explicated the obtained particles were sphere-shaped and the terpenoids of Euphorbia fischeriana had strong communications with gold surface. The HRTEM and XRD images exposed the produced gold nanoparticles had an extreme composition of crystal arrangement and excellent uniformed size of particles. In our study, the Isoprenaline induced myocardial damage established the elevation in TBARS, LOOH of heart tissues and notable decline in antioxidant enzymes SOD, CAT, GPx, and GSH. This biochemical result was additionally proved by histopathological assessment. Remarkably, the pretreatment with EF-AuNps(50 mg/kg b.w) illustrated stabilized levels of serum creatine and cardiotropins in myocardial infarcted animals. And further we understood the essential function of NF-ƙB, TNF-α, IL-6 signaling molecules and its way progression in the development of vascular tenderness.

Synthesis of New Lathyrane Diterpenoid Derivatives from Euphorbia lathyris and Evaluation of Their Anti-Inflammatory Activities.

Euphorbia factor L3 , a lathyrane diterpenoid extracted from Euphorbia lathyris, was found to display good anti-inflammatory activity with very low cytotoxicity. To find more potent anti-inflammatory drugs, two series of Euphorbia factor L3 derivatives with fatty and aromatic acids were designed and synthesized. Among them, lathyrane derivative 5n exhibited most potent inhibition on LPS-induced NO production in RAW264.7 cells with no obvious cytotoxicity. To determine the key characteristics of Euphorbia factor L3 derivatives that contribute to anti-inflammatory activity, we conducted a structure-activity relationship study of these compounds.