In vitro acetylcholinesterase, tyrosinase inhibitory potentials of secondary metabolites from Euphorbia schimperiana and Euphorbia balsamifera.

Acetylcholinesterase, tyrosinase, and α-glucosidase inhibition activities of Euphorbia schimperiana and Euphorbia balsamifera extracts, fractions, and available pure compounds were evaluated for the first time. Acetylcholinesterase assay revealed a significant inhibitory activity of E. balsamifera total extract and n-hexane fraction with 47.7% and 43.3%, respectively, compared to the reference drug, which was 75%. The n-butanol fraction demonstrated tyrosinase inhibitory activity for E. balsamifera and E. schimperiana with 36.7% and 29.7%, respectively, compared to 60% for the reference drug. Quercetin-3-O-α-glucuronide, quercetin-3-O-ß-D-glucuronide-methyl ester, quercetin-3-O-α-L-rhamnoside, 3,3'-di-O-methyl ellagic acid, 3,3'-di-O-methyl-ellagic acid-4-ß-D-xylopyranoside, and 4-O-ethyl gallic acid were identified from E. schimperiana while quercetin-3-O-glucopyranoside and isoorientin were determined from E. balsamifera. The AChE inhibitory effect of pure compounds exhibited promising activity, where 4-O-ethylgallic acid demonstrated 51.1%, while the highest tyrosinase inhibition was demonstrated by isoorientin with 50.6% compared to the reference drug (60%). Finally, a molecular docking study was performed for the most promising AChE and tyrosinase inhibitors. The extracts, fractions, and isolated compounds showed no α-glucosidase inhibitory activity.

LC-MS/MS and GC-MS based phytochemical perspectives and antimicrobial effects of endophytic fungus Chaetomium ovatoascomatis isolated from Euphorbia milii.

The antimicrobial activity of endophytic fungi isolated from Euphorbia milii was evaluated against Gram-positive, Gram-negative bacteria, unicellular yeast, and filamentous fungi. Chaetomium ovatoascomatis NRC was identified morphologically and genetically as the most active strain. The total ethyl acetate extract of C. ovatoascomatis NRC demonstrated significant antimicrobial activity against Gram-negative; Escherichia coli, Salmonella enteric, and fungi; Aspergillus niger with MIC of 62.5 ug/ml. Whereas n-hexane fraction demonstrated broader activity against Gram-positive; Bacillus subtilis, Lactobacillus cereus, Gram-negative; Escherichia coli and Salmonella enteric, fungi; Candida albicans and F. solani. LC-MS/MS analysis of ethyl acetate strain extract and GC-MS analysis of the n-hexane fraction were used to identify the metabolites of the strain extract. LC-MS/MS determined three major metabolites with potential antimicrobial activities including grevilline B, aflatoxin G2 and apigenin. GC-MS analysis of n-hexane fraction tentatively identified 30 compounds, where 9,12-octadecadienoic acid methyl ester was the major compound.

Alloimperatorin from Ammi majus fruits mitigates Piroxicam-provoked gastric ulcer and hepatorenal toxicity in rats via suppressing oxidative stress and apoptosis.

INTRODUCTION: Fruits of Ammi majus, commonly called bishop's weed, contain a significant amount of furanocoumarins. Alloimperatorin (Allo, 6) was isolated from the free coumarin fraction of fruits, beside 8-hydroxypsoralen (1), methoxsalen (2), heraclin (3), isoimperatorin (4), imperatorin (5), isoheraclenin (7) and heraclenin hydrate (8). Piroxicam (Px) is a widely used pain-relieving drug that demonstrated side effects, including gastric ulceration and hepatorenal toxicity. OBJECTIVE: This study aimed to investigate the protective potential of Alloimperatorin against Px-induced gastric ulceration and hepatorenal toxicity. MATERIAL & METHODS: Rats were divided into four groups: Negative control, Px-induced rats, Allo + Px co-treated group, and Pc + Px co-treated group. Allo (25 mg/kg body weight) and Pc (25 mg/kg body weight) treatments were received 5 days before and 4 days after Px intoxication for 4 days (50 mg/kg body weight). Serum prostaglandin E2 (PG-E2) and liver and kidney functions were measured. Oxidative stress markers were evaluated in the three tissues. Histopathological features and caspase-3 immunoexpression were monitored. RESULTS & DISCUSSION: Px triggered gastric ulceration, increased indices of liver and kidney functions, decreased PG-E2 levels, provoked oxidative stress, and activated caspase-3 immunoexpression. Co-treatment with Allo demonstrated protective activities. CONCLUSION: Alloimperatorin exhibited anti-oxidative, anti-inflammatory, and anti-apoptotic activities.

Isolation of diverse bioactive compounds from Euphorbia balsamifera: Cytotoxicity and antibacterial activity studies.

Antibacterial and cytotoxic activities of Euphorbia balsamifera, fractions and pure compounds were evaluated. The cytotoxic assays for HCT116, HePG2 and MCF7 showed a significant IC50: 54.7 and 76.2 µg/mL of non-polar fraction "n-hexane" against HCT116 and HePG2, respectively. Antibacterial results revealed that plant fractions exhibited significant potential against the tested pathogens than the total extract where n-butanol and ethyl acetate fractions showed significant antibacterial activity (P < 0.05) against tested bacterial strains. Isolation and structure determination of compounds from n-hexane and n-butanol fractions were performed. From n-hexane fraction, 29-nor-cycloartanol (1), lanost-8-en-3-ol (2a), cycloartanol (2b) and kampferol-3,4'-dimethyl ether (3) were isolated and structurally identified, along with 24 compounds were tentatively identified by GC-MS. From the polar n-butanol fraction, 4-O-ß-D-glucopyranosyl-2-hydroxy-6-methoxyacetophenone (4), 4-O-α-L-rhamnosyl-(1 â†’ 6)-ß-D-glucopyranosyl-2-hydroxy-6methoxy-acetophenone (5), quercetin-3-O-glucopyranoside (6) and isoorientin (7) were assigned. Structures of the obtained compounds were determined by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. Except compounds 1 and 5, all reported compounds announced antibacterial efficiency. Compound 2 showed selectively the highest activity against Enterococcus faecalis (22 ± 0.13 mm), meanwhile 4-O-ß-D-glucopyranosyl-2-hydroxy-6-methoxyacetophenone (4) showed broadly the highest antibacterial activity with MIC of 1.15-1.88 mg/mL against the test Gram-positive and Gram-negative bacteria. Cytotoxic assays indicated that kampferol-3,4'-dimethyl ether (3) exhibited the highest activity with matching IC50 values to doxorubicin; 111.46, 42.67 and 44.90 µM against HCT116, HePG2 and MCF7, respectively, however, it is toxic on retina normal cell line RPE1.

TH1/TH2 chemokines/cytokines profile in rats treated with tetanus toxoid and Euphorbia tirucalli.

Natural products, including their purified materials, play a remarkable role in drug development. The Euphorbiaceae family, mainly Euphorbia tirucalli, is used in some traditional medicine, and has evidence that its latex comprises immunomodulatory properties and cytokine production. This study aimed to measure the in vivo production of chemokines (IL-1α, IL-1ß, IL-12, and RANTES), TH1 cytokines (IFN-γ, TNF-α, GM-CSF, and IL-2) and TH2 cytokines (IL-4, IL-6, IL-10, and IL-13) in rats after treatments with ethanol latex extract of E. tirucalli. Vaccine treated and untreated rats were divided into seven groups to assess antimicrobial activities of the extracted components. After completion of the treatment schedule, blood was withdrawn and sera were collected. The results showed that the main component of the extract was a euphol compound. The extract showed antimicrobial activity and had the ability to modulate innate and adaptive immunity. Animals treated with extract for only 7 days before vaccination showed higher levels of antibody production. The extract showed antibacterial and antifungal activities. The extract could stimulate both adaptive and innate immunity. Pre-treatment with the extract increased immune responses in vaccinated animals, indicating the usefulness of the extract before immunization.

Comparative Correlation Between Chemical Composition and Cytotoxic Potential of the Coral-Associated Fungus Aspergillus sp. 2C1-EGY Against Human Colon Cancer Cells.

Cancer is a leading cause of death in several countries. In the search for new anticancer drugs, marine organisms have played an important role in the discovery of lead compounds and the development of new pharmaceuticals for their wide diversity of chemical structures and biological activities. In the present study, the cytotoxicity on colorectal cancer cells HCT116 exerted by marine fungus Aspergillus sp. 2C1-EGY extracts associated with the soft coral Sinularia sp. was investigated; the sub-fractions Fr 2c and Fr 2d had significantly high cytotoxic activity (88 and 85%, respectively). Moreover, the major hexadecanoic, octadecanoic, and octadecenoic acids as well as their methyl esters were isolated. GC/MS analysis revealed the identification of 46 major and minor compounds, from which 19 saturated and unsaturated fatty acids and eight fatty acid esters were identified.

Indole Alkaloids from the Sea Anemone Heteractis aurora and Homarine from Octopus cyanea.

The two new indole alkaloids 2-amino-1,5-dihydro-5-(1H-indol-3-ylmethyl)-4H-imidazol-4-one (1), 2-amino-5-[(6-bromo-1H-indol-3-yl)methyl]-3,5-dihydro-3-methyl-4H-imidazol-4-one (2), and auramine (3) have been isolated from the sea anemone Heteractis aurora. Both indole alkaloids were synthesized for the confirmation of the structures. Homarine (4), along with uracil (5), hypoxanthine (6), and inosine (7) have been obtained from Octopus cyanea.

Flavone composition and antihypercholesterolemic and antihyperglycemic activities of Chrysanthemum coronarium L.

Five flavones were isolated from Chrysanthemum coronarium L., four of which were isolated for the first time from the genus Chrysanthemum. Two were the flavonoid aglycones 5,7-dihydroxy-3,6,4'-trimethoxyflavone (1) and scutellarin-6,7-dimethyl ether (2). A new flavonoid glycoside, apigenin-7-O-[2"(6'''-O-beta-D-acetylglucopyranosyl)]-6"-O-acetylglucopyranoside (3), along with two known ones, i. e. apigenin-7-O-(2"-O-beta-D-glucopyranosyl)-beta-D-glucopyranoside (4) and 6-methoxy quercetin-7-O-beta-D-glucopyranoside (5), were identified. Structures were elucidated by NMR and MS. The therapeutic value of petroleum ether, ethyl acetate, and methanol extracts, respectively, in rats suffering from hypercholesterolemia--as a consequence of high-fat diet-and hyperglycemia--as a consequence of hypercholesterolemia and low doses of streptozotocin--was investigated through determination of biochemical markers and histopathology. The ethyl acetate and methanol extracts showed remarkable results, followed by the petroleum ether extract.

Preliminary in vitro and in vivo evaluation of antidiabetic activity of Ducrosia anethifolia Boiss. and its linear furanocoumarins.

Aim. Ducrosia anethifolia is used as flavoring additive. There have been little detailed phytochemical reports on this genus and the antidiabetic activity of this plant is not yet evaluated. Method. Structure of compounds was deduced by spectroscopic analyses. Preliminary in vitro evaluation of the antidiabetic activity of crude extract and its furanocoumarins was carried out ( α -amylase, α -glucosidase, and ß -galactosidase). The in vivo activity was investigated by measuring some oxidative stress markers. Biomarkers of liver injury and kidney were also determined. Results. Eight linear furanocoumarins, psoralen, 5-methoxypsoralen, 8-methoxypsoralen, imperatorin, isooxypeucedanin, pabulenol, oxypeucedanin methanolate, oxypeucedanin hydrate, and 3-O-glucopyranosyl- ß -sitosterol, were isolated. All compounds were reported for the first time from the genus Ducrosia except pabulenol. The blood glucose level, liver function enzymes, total protein, lipid, and cholesterol levels were significantly normalized by extract treatment. The antioxidant markers, glucolytic, and gluconeogenic enzymes were significantly ameliorated and the elevated level of kidney biomarkers in the diabetic groups was restored. The compounds showed inhibitory activity in a concentration dependant manner. Imperatorin and 5-methoxypsoralen showed the most potent inhibiting power. Conclusion. D. anethifolia extract showed hypoglycemic, hypolipidemic, and antioxidant effect as well as ameliorating kidney function. This extract and some linear furanocoumarins exhibited carbohydrate metabolizing enzymes inhibitory effect.

Beetles do it differently: two stereodivergent cyclisation modes in iridoid-producing leaf-beetle larvae.

Larvae of the Chrysomelina species Phaedon cochleariae, Hydrothassa marginella, Phratora vulgatissima, Gastrophysa viridula, Gastrophysa atrocyanea, Gastrophysa cyanea and Gastrophysa polygoni produce the iridoid chrysomelidial (1) to defend themselves against predators. Feeding experiments with a deuterated precursor ([(2)H(5)]8-hydroxygeraniol 9) and in vitro isotope exchange experiments with defensive secretion in (2)H(2)O revealed differences in the cyclisation of the ultimate precursor 8-oxogeranial (8) to 1, between members of the genus Gastrophysa and all other species. In P. cochleariae, H. marginella and P. vulgatissima 1 is most likely produced by a Rauhut-Currier-type cyclisation via a "transoid dienamine", with loss of a single deuterium atom from C(4) of the precursor. In contrast, members of the genus Gastrophysa cyclise 8 via a "cisoid dienamine" intermediate, with exchange of all three deuterium atoms from the methyl group at C(3). To study whether the different cyclisation modes influence the stereochemistry of 1, the absolute configuration of 1 of the larvae was determined by GC-MS on a chiral column. In accordance with literature (J. Meinwald, T. H. Jones, J. Am. Chem. Soc. 1978, 100, 1883 and N. Shimizu, R. Yakumaru, T. Sakata, S. Shimano, Y. Kuwahara, J. Chem. Ecol. 2012, 38, 29), we found (5S,8S)-chrysomelidial (1) in H. marginella and P. vulgatissima, but P. cochleariae and all investigated members of the genus Gastrophysa synthesise (5R,8R)-chrysomelidial (1).

Environmental stresses of field growth allow cinnamyl alcohol dehydrogenase-deficient Nicotiana attenuata plants to compensate for their structural deficiencies.

The organized lignocellulosic assemblies of cell walls provide the structural integrity required for the large statures of terrestrial plants. Silencing two CINNAMYL ALCOHOL DEHYDROGENASE (CAD) genes in Nicotiana attenuata produced plants (ir-CAD) with thin, red-pigmented stems, low CAD and sinapyl alcohol dehydrogenase activity, low lignin contents, and rubbery, structurally unstable stems when grown in the glasshouse (GH). However, when planted into their native desert habitat, ir-CAD plants produced robust stems that survived wind storms as well as the wild-type plants. Despite efficient silencing of NaCAD transcripts and enzymatic activity, field-grown ir-CAD plants had delayed and restricted spread of red stem pigmentation, a color change reflecting blocked lignification by CAD silencing, and attained wild-type-comparable total lignin contents. The rubbery GH phenotype was largely restored when field-grown ir-CAD plants were protected from wind, herbivore attack, and ultraviolet B exposure and grown in restricted rooting volumes; conversely, it was lost when ir-CAD plants were experimentally exposed to wind, ultraviolet B, and grown in large pots in growth chambers. Transcript and liquid chromatography-electrospray ionization-time-of-flight analysis revealed that these environmental stresses enhanced the accumulation of various phenylpropanoids in stems of field-grown plants; gas chromatography-mass spectrometry and nuclear magnetic resonance analysis revealed that the lignin of field-grown ir-CAD plants had GH-grown comparable levels of sinapaldehyde and syringaldehyde cross-linked into their lignins. Additionally, field-grown ir-CAD plants had short, thick stems with normal xylem element traits, which collectively enabled field-grown ir-CAD plants to compensate for the structural deficiencies associated with CAD silencing. Environmental stresses play an essential role in regulating lignin biosynthesis in lignin-deficient plants.

Phaseoloidin, a homogentisic acid glucoside from Nicotiana attenuata trichomes, contributes to the plant's resistance against lepidopteran herbivores.

Plant trichomes are known for their capability to produce and store secondary metabolites that protect plants from biotic and abiotic stresses. (1)H NMR studies on intact individual trichomes located on the leaf surface of Nicotiana attenuata revealed the presence of two major secondary metabolites: nicotine, the signature metabolite of the genus, and phaseoloidin, a homogentisic acid glucoside. This glucoside was reported originally from the seeds of Entada phaseoloides, and this is the first report of its occurrence in a Solanaceous plant. Artificial diet feeding bioassays with Manduca sexta and Spodoptera littoralis larvae, two important herbivores of N. attenuata, revealed that the ingestion of phaseoloidin negatively influenced caterpillar performance. This effect was more pronounced for the generalist, S. littoralis, than for the specialists, M. sexta.

Bioactive metabolites from the sponge Suberea sp.

Two new brominated compounds, subereaphenol K (2) and 2-(3,5-dibromo-1-ethoxy-4-oxocyclohexa-2,5-dien-1-yl)acetamide (3), together with subereaphenol B (methyl 2-(2,4-dibromo-3,6-dihydroxyphenyl)acetate; 1) with a revised structure, and five dibromotyrosine-derived metabolites, 4-8, were isolated from the sponge Suberea sp. and characterized by 1D- and 2D-NMR spectroscopic and HR-MS spectrometric data. Compounds 1, 2, 6, and 8 exhibited various weak or moderate bioactivities, including antimicrobial and cytotoxic activities. Furthermore, compounds 1 and 2 inhibited human recombinant phosphodiesterase 4 (PDE4) with IC50 values of 2 µM, whereas compounds 6 and 8 were less active.

Phenolic glucosides from Hasseltia floribunda.

The leaves of Hasseltia floribunda were examined for their chemical constituents. Twelve phenolic glucosides, namely three hydroxycyclohexenyl acyl glucosides, four acylated salicortin derivatives, and five coumaroyl salicin derivatives, were isolated along with eight known phenolic glycosides, six known flavones, and two known sesquiterpenoid cyclohexenone derivatives. The structures of the isolated compounds were elucidated by NMR spectroscopic and HRMS spectrometric methods and by comparing analytical data with those of related structures.

Terpenes from the soft corals Litophyton arboreum and Sarcophyton ehrenbergi.

The new cembrane diterpene (3E,11E)-cembra-3,8(19),11,15-tetraene-7alpha-ol (1), nephthenol (2), and all-trans-peridinin (3) have been isolated from the soft coral Litophyton arboreum. The tetraterpene 3, (+)-7,8-epoxy-7,8-dihydrocembrene C (4), emblide (5), sarcophytoxide (6), sarcoglaucol-16-one (7), guajacophine (8), and 1,4-peroxymuurol-5-ene (9) have been obtained from the soft coral Sarcophyton ehrenbergi. The compounds were characterized primarily by NMR spectroscopy. Some of the terpenes were tested for their antiproliferative activity against the cell lines HUVEC and K-562 and for cytotoxicity against the cell line HeLa, and they showed moderate activities.

Synthesis, anti-inflammatory, analgesic and anticonvulsant activities of 1,8-dihydro-1-ary1-8-alkyl pyrazolo(3,4-b)indoles.

A series of 1,8-dihydro-1-aryl-8-alkyl pyrazolo(3,4-b)indoles 4a-j, 5a-j and 6a-j has been synthesized and tested for their anti-inflammatory and anticonvulsant activities. Formation of the pyrazoloindole derivatives was achieved by treating arylhydrazones of N-alkyl indole-3-carbox-aldehydes 1a-j, 2a-j and 3a-j with ten times their mass of polyphosphoric acid as a condensing agent. The newly synthesized compounds were evaluated for their anti-inflammatory, analgesic and anticonvulsant activities compared to indomethacin, flufenamic acid and diazepam as positive controls. Detailed synthesis, spectroscopic and toxicity data are reported.

Cross-reactivity of Schistosoma mansoni-Fasciola gigantica influenced by saponins.

The aim of the present work was to investigate the Schistosoma mansoni and Fasciola gigantica cross-reactivity between adult worms and egg homogenates of the parasites. Immunoprophylactic effects of crude Schistosoma mansoni worms and egg antigens mixed with or without saponins extracted from Atriplex nummularia were studied followed by challenge with 80 cercariae of Schistosoma mansoni. Our results showed that post 1st immunization with schistosome egg antigens (SEA) there was a significant change (P approximately 0.05) in the IgM levels against Fasciola egg homogenate (FgEH) without saponins. Post 2nd immunization with SEA mixed with saponins the levels of IgM increased significantly (P approximately 0.05) against Fasciola worm homogenate (FgWH) as compared with a non-immunized group. Post 2nd immunization the level of IgG was significantly elevated (P approximately 0.05) by SEA mixed with saponins against FgWH. Post 2nd immunizations with SEA mixed with saponins showed a significant change (P approximately 0.05) in IgG levels against FgEH. These results clearly demonstrated that there is a cross-reactivity between Schistosoma mansoni eggs and Fasciola gigantica worms and eggs. Saponins were found to be immunostimulatory adjuvants in our study.

Cembranoid diterpenes and a briarane diterpene from corals.

Two new cembrane diterpenes (+)-polydactylide (1) and (+)-7alpha,8beta-dihydroxydeepoxysarcophine (2) together with (+)-sarcophine (3) and (+)-sarcophytoxide (4) have been isolated from the soft coral Sinularia polydactyla. The new cembrane diterpene (-)-7beta-hydroxy-8alpha-methoxydeepoxysarcophine (5) has been obtained from the soft coral Sarcophyton trocheliophorum and the known briarane diterpene briaexcavatolide W (6) from the gorgonian coral Briareum sp.The structures were determined primarily by NMR spectroscopy. The assignment of NMR signals was performed by means of (1)H-(1)H COSY, ROESY, HMQC and HMBC experiments.

Titerpenoid saponins from Atriplex semibaccata.

Four new triterpenoid saponins, 3-O-([beta-D-glucopyranosyl-(1-->2)]-beta-D-galactopyranosyl)-11alpha-methoxy-23-hydroxylongispinogenin, 3-O-([beta-D-glucopyranosyl-(1-->2)]-beta-D-galactopyranosyl)-11alpha-methoxy-23,29-dihydroxylongispinogenin, 3-O-([beta-D-glucopyranosyl-(1-->2)]-beta-D-galactopyranosyl)-29-hydroxysaikogenin F and 3-O-([beta-D-glucopyranosyl-(1-->2)]-beta-D-galactopyranosyl)-saikogenin F, have been isolated from Atriplex semibaccata. The structures were determined primarily by NMR spectroscopy. The assignment of NMR signals was performed by means of 1H-1H COSY, ROESY, HMQC and HMBC experiments.