查看更多>>摘要：? 2022 Elsevier LtdDivinyl ether synthases (DESs) are the enzymes occurring in numerous plant species and catalysing the dehydration of fatty acid hydroperoxides to divinyl ether oxylipins, playing self-defensive and antipathogenic roles in plants. Previously, the DES activities and divinyl ethers were detected in some monocotyledonous plants, including the asparagus (Asparagus officinalis L.). The cloning of the open reading frame of the CYP74H2 gene of asparagus and catalytic properties of the recombinant CYP74H2 protein are described in the present work. The CYP74H2 utilized the 13(S)-hydroperoxide of linoleic acid (13(S)-HPOD) as a preferred substrate and specifically converted it to the divinyl ether, (9Z,11Z)-12-[(1?E)-hexenyloxy]-9,11-dodecadienoic acid, (11Z)-etheroleic acid. The second most efficient substrate after the 13(S)-HPOD was the 9(S)-hydroperoxide of α?linolenic acid (9(S)-HPOT), which was converted to the previously undescribed product, (1?Z)-colnelenic acid. The 13(S)-hydroperoxide of α?linolenic acid (13(S)-HPOT) and 9(S)-hydroperoxide of linoleic acid (9(S)-HPOD) were less efficient substrates for CYP74H2. Both 13(S)-HPOT and 9(S)-HPOD were transformed to divinyl ethers, (11Z)-etherolenic and (1?Z)-colneleic acids, respectively. The CYP74H2 is a second cloned monocotyledonous DES after the garlic CYP74H1 and the first DES biosynthesizing the (1?Z)-colneleic and (1?Z)-colnelenic acids.
查看更多>>摘要：? 2022 Elsevier LtdAuxin is a key regulator of plant development and in Arabidopsis thaliana can be synthesized through multiple pathways; however, the contributions of various biosynthetic pathways to specific developmental processes are largely unknown. To trace the involvement of various biosynthetic routes to indole-3-acetic acid (IAA) under conditions that induce adventitious root formation in Arabidopsis hypocotyls, we treated seedlings with three different stable isotope-labeled precursors ([13C6]anthranilate, [15N1]indole, and [13C3]serine) and monitored label incorporation into a number of proposed biosynthesis intermediates as well as IAA. We also employed inhibitors targeting tryptophan aminotransferases and flavin monooxygenases of the IPyA pathway, and treatment with these inhibitors differentially altered the labeling patterns from all three precursors into intermediate compounds and IAA. [13C3]Serine was used to trace utilization of tryptophan (Trp) and downstream intermediates by monitoring 13C incorporation into Trp, indole-3-pyruvic acid (IPyA), and IAA; most 13C incorporation into IAA was eliminated with inhibitor treatments, suggesting Trp-dependent IAA biosynthesis through the IPyA pathway is a dominant contributor to the auxin pool in de-etiolating hypocotyls that can be effectively blocked using chemical inhibitors. Labeling treatment with both [13C6]anthranilate and [15N1]indole simultaneously resulted in higher label incorporation into IAA through [15N1]indole than through [13C6]anthranilate; however, this trend was reversed in the proposed precursors that were monitored, with the majority of isotope label originating from [13C6]anthranilate. An even greater proportion of IAA became [15N1]-labeled compared to [13C6]-labeled in seedlings treated with IPyA pathway inhibitors, suggesting that, when the IPyA pathway is blocked, IAA biosynthesis from labeled indole may also come from an origin independent of the measured pool of Trp in these tissues.
查看更多>>摘要：? 2022Berberine alkaloids belong to the class of isoquinoline alkaloids that have been shown to possess anticancer potential, berberine exhibits inhibitory effects on breast cancer development. However, the exact mechanisms of action for anti-breast carcinoma of the alkaloids, including epiberberine, berberrubine and dihydroberberine are still unclear. MTT assay, colony formation, wound healing and transwell invasion assays detected these alkaloids suppressed proliferation, migration and invasion of breast cancer cells. Hoechst and Annexin V-FITC/PI staining were used to analyze the apoptosis of breast cancer cells. Western blotting investigated the changes noted in the expression levels of the key proteins involved in the Wnt/β-catenin signaling pathway and epithelial to mesenchymal transition (EMT). The results showed that inhibited the proliferation of breast cancer cells. Berberine alkaloids inhibited the cell cycle at G2/M phase in MCF-7 cells, but in MDA-MB-231 cells berberine alkaloids arrested the cell cycle in G0/G1 and G2/M phases. By decreasing β-catenin expression, increasing GSK-3β expression and decreasing N-cadherin expression, increasing E-cadherin expression, which proved that epiberberine, berberrubine and dihydroberberine inhibited of metastasis of breast cancer cells through Wnt signaling pathway and reversed EMT except berberine. Furthermore, berberine alkaloids exert their anti-breast cancer effects through the synergistic action of intrinsic and extrinsic pathways of apoptosis. These findings highlight the different effects of different berberine alkaloids on breast cancer cells and confirm that berberine alkaloids may be potentially used in the treatment of breast cancer.
查看更多>>摘要：? 2022 Elsevier LtdSeven undescribed lignans, equiselignan A–F, and six undescribed terpenoids, equiseterpenoid A–E (including two pairs of enantiomers, (+/?)-equiselignan A and (+/?)-equiseterpenoid E), were isolated from the stems of Ephedra equisetina Bunge. Their structures were elucidated by spectroscopic methods, and the absolute configurations of the undescribed compounds were determined by interpretation of their electronic circular dichroic (ECD) and optical rotation data. In β-hexosaminidase (β-Hex) release assay, anti-asthmatic activities of all of the compounds were evaluated by releasing β-Hex in C48/80-induced RBL-2H3 cells. The β-Hex release rates of equiselignan B and equiseterpenoid B were 0.86 ± 0.094 and 0.86 ± 0.012 by comparing with model group, whereupon equiselignan B and equiseterpenoid B exhibited significant anti-asthmatic activities.
查看更多>>摘要：? 2022 Elsevier LtdMetabolism of special endophytes and phytopathogens can be induced by the symbiotic interactions with the host. A phytopathogen Epicoccum sorghinum cultured in host mushroom Thelephora ganbajun medium exhibited different metabolites compared with that of ordinary medium. An unprecedented scaffold possessing the same substructure as perylenequinone mycotoxin, a first methyl rearrangement product of phytotoxin, epoxydon 6-methylsalicylate ester, three undescribed compounds, and an undescribed natural product were isolated from E. sorghinum cultured in T. ganbajun. Episorin A and epicosorin A were produced from E. sorghinum induced by culturing in host medium. Episorin A was the first example of perylenequinone analogue in the natural products. These induced compounds and other metabolites showed notable antibiosis against endogenous fungi, and insect existing in mushroom. Induced episorin A showed significant inhibitory effects on nitric oxide production in LPS-activated macrophages, and anti-acetylcholinesterase with the IC50 at 5.40 ± 0.25 μM, and 4.32 μM, respectively, and cytotoxicity against HL-60, A-549, SMMC-7721, MCF-7 and SW480 with IC50 at 14.21 ± 0.53, 17.93 ± 0.22, 18.17 ± 0.63, 28.36 ± 0.43, and 18.20 ± 1.03 μM.
查看更多>>摘要：? 2022 Elsevier LtdThe study of floral trait diversity has a long history due to its role in angiosperm diversification. While many studies have focused on visual traits including morphology and color, few have included floral scent despite its importance in pollination. Of the studies that have included floral scent, sampling has been limited and rarely explores variation at the population level. We studied geographic variation in the flowers of Oenothera harringtonii, a rare plant endemic to a vulnerable shortgrass prairie habitat, whose population structure and conservation status are well studied. The self-incompatible flowers of O. harringtonii open at dusk, produce nectar and a strong fragrance, and are pollinated by hawkmoths. We collected floral trait (morphology, scent chemistry and emission rates) data from 650 individuals from 19 wild populations to survey floral variation across the entire range of this species. Similarly, we collected floral data from 49 individuals grown in a greenhouse common garden, to assess whether variation observed in the field is consistent when environment factors (temperature, watering regime, soil) are standardized. We identified 35 floral volatiles representing 5 biosynthetic classes. Population differentiation was stronger for floral scent chemistry than floral morphology. (R)-(?)-linalool was the most important floral trait differentiating populations, exhibiting clinal variation across the distribution of O. harringtonii without any correlated shifts in floral morphology. Populations in the north and west produced (R)-(?)-linalool consistently, those in the east and south largely lacked it, and populations at the center of the distribution were polymorphic. Floral scent emissions in wild populations varied across four years but chemical composition was largely consistent over time. Similarly, volatile emission rates and chemical composition in greenhouse-grown plants were consistent with those of wild populations of origin. Our data set, which represents the most extensive population-level survey of floral scent to date, indicates that such sampling may be needed to capture potentially adaptive geographic variation in wild populations.
查看更多>>摘要：? 2022 Elsevier LtdThis study aimed to report the structure elucidation of the compounds isolated from Salvia miltiorrhiza, and their biological evaluations. Ten undescribed diterpenoid quinones and 10 known analogues were isolated from the dried roots of S. miltiorrhiza. Their structures were elucidated by extensive analysis, including nuclear magnetic resonance, high-resolution mass spectra, and ultraviolet and infrared spectra. Their absolute configurations were determined by comparing the experimental and calculated electronic circular dichroism spectra. In the evaluation of bioactivities, Salvianolactone acid I, epi-danshenspiroketallactone F, danshinspiroketallactone, grandifolia G, and 2H-Naphtho [1,8-bc]furan (10 μM) significantly increased cell viability and decreased the nuclear transport of p-P65 in lipopolysaccharide-induced bronchial epithelial cells. It was concluded that the diterpenoid quinones might belong to potent targeted lung-protective agents.
查看更多>>摘要：? 2022Cannabis sativa is a versatile crop that can be cultivated for fiber, seed, or phytochemicals. To take advantage of this versatility and the potential of Cannabis as a feedstock for the bioeconomy, genomics-enabled breeding programs must be strengthened and expanded. This work contributes to the foundation for such by investigating the phytochemistry and genomics of feral Cannabis populations collected from seventeen counties across the climate gradient of Nebraska. Flower tissue from male and female plants (28 total) was studied using (i) gas chromatography-mass spectrometry to assess cannabinoid profiles and (ii) RNA sequencing to determine transcript abundances. Both male and female flower tissues produced cannabinoids, and, though the compounds were more abundant in female flower tissue, the primary cannabinoid in both was usually cannabidiol. The expression of genes that mediate early steps on the cannabinoid biosynthetic pathway were upregulated in female relative to male flowers, suggesting that female versus male flower tissue cannabinoid abundance may be controlled at least in part at the transcriptional level. DNA sequencing was used to place feral Cannabis plants from Nebraska into a previously described genomic context, revealing that all the plants studied here are much more similar to previously characterized hemp-type Cannabis plants than to drug-type Cannabis plants, at least at the genetic level. This work provides foundational phytochemical knowledge and a large set of high-quality single nucleotide polymorphism markers for future studies of feral Nebraska Cannabis.
查看更多>>摘要：? 2022 Elsevier LtdKirsten rat sarcoma viral oncogene homolog (KRAS) mutation is one of the most important carcinogenic factors in many solid tumors, which leads to the poor prognosis and therapy resistance of cancer. In order to develop direct or indirect KRAS inhibitors, one unique asymmetric dicyclopentenone penipentenone A, three undescribed brefeldin A (BFA) derivatives, and five known BFA derivatives were discovered from the endophytic fungus Penicillium brefeldianum guided by LC-MS/MS and cytotoxic activities. Their structures were elucidated by optical rotation, mass spectrometry, and NMR spectroscopic data. The absolute configurations of four undescribed compounds were elucidated by comparison of the experimental and calculated ECD spectra. The antiproliferative activities of obtained compounds against three KRAS mutant tumor cell lines and two BFA derivative-sensitive cell lines were evaluated. Besides 4-epi-15-epi-brefeldin A, the other compounds showed significant inhibitory activities against those tumor cell lines with IC50 values ranging from 0.82 to 18.87 μM. Intriguingly, penipentenone A selectively inhibited KRAS mutant cancer cells SW620 (KRASG12V) and ASPC-1 (KRASG12D). BFA and four derivatives showed potent cytotoxic activities against all selected tumor cell lines H358 (KRASG12C), SW620 (KRASG12V), ASPC-1 (KRASG12D), PC-3, and HepG-2. These findings will provide undescribed lead compounds for developing drugs that target KRAS mutations.
查看更多>>摘要：? 2022 Elsevier LtdCannabis is used to treat various medical conditions, and lines are commonly classified according to their total concentrations of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Based on their ratio of total THC to total CBD, cannabis cultivars are commonly classified into high-THC, high-CBD, and hybrid classes. While cultivars from the same class have similar compositions of major cannabinoids, their levels of other cannabinoids and their terpene compositions may differ substantially. Therefore, a more comprehensive and accurate classification of medicinal cannabis cultivars, based on a large number of cannabinoids and terpenes is needed. For this purpose, three different chemometric-based classification models were constructed using three sets of chemical profiles. We examined those models to determine which provides the most accurate “chemovar” classification. This was done by analyzing profiles of cannabinoids, terpenes, and the combination of these substances using the partial least square-discriminant analysis multivariate (PLS-DA) technique. The chemical profiles were selected from the three major classes of medicinal cannabis that are most commonly prescribed to patients in Israel: high-THC, high-cannabigerol (CBG), and hybrid. We studied the correlations between cannabinoids and terpenes to identify major bio-indicators representing the plant's terpene and cannabinoid content. All three PLS-DA models provided highly accurate classifications, utilizing six to nine latent variables with an overall accuracy ranging from 2 to 11% CV. The PLS-DA model applied to the combined cannabinoid-and-terpene profile did the best job of differentiating between the chemovars in terms of misclassification error, sensitivity, specificity, and accuracy. The combined cannabinoid-and-terpene PLS-DA profile had cross-validation and prediction misclassification errors of 4% and 0%, respectively. This is the first study to demonstrate the highly accurate classification of samples of medicinal cannabis based on their cannabinoid and terpene profiles, as compared to cannabinoid profiles alone. Furthermore, our correlation analysis indicated that 11 cannabinoids and terpenes might serve as bio-indicators for 32 different active compounds. These findings suggest that the use of multivariate statistics could assist in breeding studies and serve as a tool for minimizing the mislabeling of cannabis inflorescences.
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