Structural elucidation and complete NMR spectral assignments of Monascus monacolin analogues.

Three new monacolin analogues, 3,6-dihydroxy-monacolin P (1), 6-methoxy monacolin S (2), and 6-methoxy dehydromonacolin S (3), were isolated from a fraction that strongly inhibited 3-hydroxy-3-methylglutaryl-CoA reductase from the ethyl acetate portion of red yeast rice ethanol extract. Their structures were determined through a combination of 1D and 2D NMR experiments, mass spectrometry analysis, and known literature reports.

Triterpene esters of cirsium setosum and their anti-inflammatory activity.

Two new triterpene fatty acid esters, 3ß-palmityloxy-12,27-cyclofriedoolean-14-en-11α-ol (1) and 3ß-palmityloxy-19α-hydroxyursane (2), together with 3ß-hydroxy-11-oxo-olean-12-enyl palmitate (3) were isolated from the potent anti-inflammatory active fraction of the petroleum ether-soluble part of Cirsium setosum ethanol extract. Compound 1 was found to be a rare 12,27-cyclopropane triterpenoid. Their structures were determined through spectral data analysis combined with literature reports. Furthermore, in vitro experiment, compounds 1-3 exhibited significant inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages.

The potential role of nondigestible Raffinose family oligosaccharides as prebiotics.

Based on factual scientific health claims, prebiotics have gained significant importance in ever-growing food and pharmaceutical industries. The diverse nature of distinct prebiotics influences the host differently in distinguishable patterns. Functional oligosaccharides are either plant-derived or commercially prepared. Raffinose, stachyose, and verbascose are the 3 types of raffinose family oligosaccharides (RFOs) that have been extensively used as medicine, cosmetic, and food additives. These dietary fiber fractions avert the adhesion and colonization by enteric pathogens and add nutrition metabolites for a healthy immune system. Enrichment of RFOs in healthy foods should be promoted as these oligosaccharides augment gut microecology by enhancing the health conferring microbes i.e. bifidobacteria and lactobacilli. RFOs influence the host's multiorgan systems due to their physiological and physicochemical properties. For example, the fermented microbial products of such carbohydrates affect neurological processes, including memory, mood, and behavior in humans. Raffinose-type sugar uptake is thought to be a ubiquitous property of bifidobacteria. This review paper summarizes the source of RFOs and their metabolizing entities, highlighting bifidobacterial carbohydrate utilization and health benefits.

Two unusual novel iridoid glycosides from Cornus officinalis fruit and their biological activities.

Two unusual novel iridoid glycosides, cornsecoside A (1) and cornsecoside B (2), were isolated from a 40% ethanol elution fraction of a 50% ethanol extract of Cornus officinalis fruit. Their structures were determined by spectroscopic data analysis combined with hydrolysis and ECD spectroscopy. In addition, compounds 1 and 2 exhibited cytotoxic activity against Bel-7402 cells with IC50 values of 8.12 and 9.31 µM, and were neuroprotective against H2O2-induced SH-SY5Y cell injure at a concentration of 10 µM.

Screening of Siderophore-Producing Bacteria and Their Effects on Promoting the Growth of Plants.

Iron deficiency is a major global agricultural problem. Siderophores can help organisms to uptake iron in form of siderophore-Fe3+ complexes and then in the cell cytosol, iron is reducted and released in ferrous form. This research aimed to obtain some efficient siderophore-producing bacterial strains and evaluate their plant growth-promoting effects in the iron-deficit environment. Two strains, Brucella sp. E7 and Pseudomonas brassicae W7, were isolated from rhizosphere soil. Both strains could produce maximum siderophores under the optimal conditions. Plant promoting experiment showed that many indicators of Vigna radiata seedling were all increased significantly by strain E7/W7 or the consortium of E7 + W7. Under no-iron and high iron stress, the inoculation treatment also showed growth promotion effects on both Vigna radiata and Lolium multiflorum. These results indicated that the potential ability of strain E7 and W7 in increasing agricultural production as a growth-promoting agent in iron-deficit soil.

Chemical characterization of a PD-1/PD-L1 inhibitory activity fraction of the ethanol extract from Gymnadenia conopsea.

Searching for PD-1/PD-L1 inhibitor from medicinal plants has become a potential method to discover small molecular cancer immunotherapy drugs. Using PD-1/PD-L1 inhibitory activity assay in vitro, a bioactive fraction was obtained from the ethanol extract of Gymnadenia conopsea. A sensitive UPLC-HRMS/MS method was established for the rapid screening and identification of compositions from bioactive fraction. Based on the characteristic fragmentation patterns of standards analysis and extracted ion chromatogram (EIC) method, 46 compounds were rapidly screened and identified (including 35 succinic acid ester glycosides and 11 other compounds), among which 17 compounds were tentatively identified as new compounds.

Rapid Characterizaiton of Chemical Constituents of the Tubers of Gymnadenia conopsea by UPLC-Orbitrap-MS/MS Analysis.

Gymnadenia conopsea R. Br. is a traditional Tibetan medicinal plant that grows at altitudes above 3000 m, which is used to treat neurasthenia, asthma, coughs, and chronic hepatitis. However, a comprehensive configuration of the chemical profile of this plant has not been reported because of the complexity of its chemical constituents. In this study, a rapid and precise method based on ultra-high performance liquid chromatography (UPLC) combined with an Orbitrap mass spectrometer (UPLC-Orbitrap-MS/MS) was established in both positive- and negative-ion modes to rapidly identify various chemical components in the tubers of G. conopsea for the first time. Finally, a total of 91 compounds, including 17 succinic acid ester glycosides, 9 stilbenes, 6 phenanthrenes, 19 alkaloids, 11 terpenoids and steroids, 20 phenolic acid derivatives, and 9 others, were identified in the tubers of G. conopsea based on the accurate mass within 3 ppm error. Furthermore, many alkaloids, phenolic acid derivates, and terpenes were reported from G. conopsea for the first time. This rapid method provides an important scientific basis for further study on the cultivation, clinical application, and functional food of G. conopsea.

Rapid Characterization of Chemical Components in Edible Mushroom Sparassis crispa by UPLC-Orbitrap MS Analysis and Potential Inhibitory Effects on Allergic Rhinitis.

Sparassis crispa is a kind of edible fungus widely grows in the north temperate zone, which shows various medicinal properties. Due to the complexity of chemical constitutes of this species, few investigations have acquired a comprehensive configuration for the chemical profile of it. In this study, a strategy based on ultra-high performance liquid chromatography (UPLC) combined with Orbitrap mass spectrometer (MS) was established for rapidly characterizing various chemical components in S. crispa. Through the summarized MS/MS fragmentation patterns of reference compounds and systematic identification strategy, a total of 110 components attributed to six categories were identified for the first time. Moreover, allergic rhinitis (AR) is a worldwide inflammatory disease seriously affecting human health, and the development of drugs to treat AR has been a topic of interest. It has been reported that the extracts of S. crispa showed obvious inhibitory effects on degranulation of mast cell- and allergen-induced IgE and proinflammatory mediators, but the active components and specific mechanism were still not clear. Src family kinases (SFKs) participate in the initial stage of allergy occurrence, which are considered the targets of AR treatment. Herein, on the basis of that self-built chemical database, virtual screening was applied to predict the potential SFKs inhibitors in S. crispa, using known crystal structures of Hck, Lyn, Fyn, and Syk as receptors, followed by the anti-inflammatory activity evaluation for screened hits by intracellular calcium mobilization assay. As results, sparoside A was directly confirmed to have strong anti-inflammatory activity with an IC50 value of 5.06 ± 0.60 µM. This study provides a useful elucidation for the chemical composition of S. crispa, and demonstrated its potential inhibitory effects on AR, which could promote the research and development of effective agents from natural resources.

Lignans from the Twigs of Litsea cubeba and Their Bioactivities.

Litsea cubeba, an important medicinal plant, is widely used as a traditional Chinese medicine and spice. Using cytotoxicity-guided fractionation, nine new lignans 1⁻9 and ten known analogues 10⁻19 were obtained from the EtOH extract of the twigs of L. cubeba. Their structures were assigned by extensive 1D- and 2D-NMR experiments, and the absolute configurations were resolved by specific rotation and a combination of experimental and theoretically calculated electronic circular dichroism (ECD) spectra. In the cytotoxicity assay, 7',9-epoxylignans with feruloyl or cinnamoyl groups (compounds 7⁻9, 13 and 14) were selectively cytotoxic against NCI-H1650 cell line, while the dibenzylbutyrolactone lignans 17⁻19 exerted cytotoxicities against HCT-116 and A2780 cell lines. The results highlighted the structure-activity relationship importance of a feruloyl or a cinnamoyl moiety at C-9' or/and C-7 ketone in 7',9-epoxylignans. Furthermore, compound 11 was moderate active toward protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 13.5 µM, and compounds 4⁻6, 11 and 12 displayed inhibitory activity against LPS-induced NO production in RAW264.7 macrophages, with IC50 values of 46.8, 50.1, 58.6, 47.5, and 66.5 µM, respectively.

Sesquiterpenoids and Their Anti-Inflammatory Activity: Evaluation of Ainsliaea yunnanensis.

Four new sesquiterpenoids (1-4) and six known sesquiterpenoids (5-10), were isolated from the EtOAc phase of the ethanolic extract of Ainsliaea yunnanensis. Their structures were established by spectroscopic methods, including 1-D, 2-D NMR and HPLC-MS. All compounds were tested for their anti-inflammatory effect by the inhibition of the activity of NLRP3 inflammasome by blocking the self-slicing of pro-caspase-1, which is induced by nigericin, then the secretion of mature IL-1ß, mediated by caspase-1, was suppressed. Unfortunately none of the compounds showed an anti-inflammatory effect.

Bioassay-Guided Isolation of Triterpenoids as α-Glucosidase Inhibitors from Cirsium setosum.

Cirsium setosum (C. setosum) has a potential antihyperglycemic effect, but it is unclear what bioactive components play a key role. According to the α-glucosidase inhibition activity, three new taraxastane-type triterpenoids of 3ß-hydroxy-30-hydroperoxy-20-taraxastene (1), 3ß-hydroxy-22α-methoxy-20-taraxastene (2), and 30-nor-3ß,22α-dihydroxy-20-taraxastene (3), as well as five known taraxastane triterpenoids of 3ß,22-dihydroxy-20-taraxastene (4), 20-taraxastene-3,22-dione (5), 3ß-acetoxy-20-taraxasten-22-one (6), 3ß-hydroxy-20-taraxasten-22-one (7), and 30-nor-3ß-hydroxy-20-taraxastene (8) were obtained from the petroleum ether-soluble portion of the ethanol extract from C. setosum. All chemical structures of the compounds were elucidated by spectroscopic data analysis and compared with literature data. Compounds 4-8 were identified for the first time from this plant, and compounds 1, 2, 4, and 7 exhibited more potent α-glucosidase inhibitory activity-with IC50 values of 18.34 ± 1.27, 26.98 ± 0.89, 17.49 ± 1.42, and 22.67 ± 0.25 µM, respectively-than acarbose did (positive control, IC50 42.52 ± 0.32 µM).

New Iridoid Derivatives from the Fruits of Cornus officinalis and Their Neuroprotective Activities.

Three previously undescribed iridoids, cornusfurals A⁻C, were isolated from the ethanolic extracts of fruits of Cornus officinalis. Their structures were elucidated by spectroscopic methods, including one-dimensional and two-dimensional nuclear magnetic resonance, ultraviolet spectroscopy, infrared spectroscopy, and mass spectrometry. The neuroprotective activity was evaluated by measuring corticosterone-induced damage in PC12 cells. The results showed that cornusfural B decreased corticosterone-induced PC12 cell damage compared with that in model cells.

Identification and Proposed Relative and Absolute Configurations of Niphimycins C-E from the Marine-Derived Streptomyces sp. IMB7-145 by Genomic Analysis.

Analysis of the whole genome sequence of Streptomyces sp. IMB7-145 revealed the presence of seven type I polyketide synthase biosynthetic gene clusters, one of which was highly homologous to the biosynthetic gene cluster of azalomycin F. Detailed bioinformatic analysis of the modular organization of the PKS gene suggested that this gene is responsible for niphimycin biosynthesis. Guided by genomic analysis, a large-scale cultivation ultimately led to the discovery and characterization of four new niphimycin congeners, namely, niphimycins C-E (1-3) and 17-O-methylniphimycin (4). The configurations of most stereocenters of niphimycins have not been determined to date. In the present study, the relative configurations were elucidated by spectroscopic analysis, including J-based analysis and the CNMR database method. Further, the full absolute configurations of niphimycins were completely proposed for the first time based on biosynthetic gene cluster analysis of the ketoreductase and enoylreductase domains for hydroxy- and methyl-bearing stereocenters. Compounds 1, 3, 4, and niphimycin Iα (5) showed antimicrobial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci (MIC: 8-64 µg/mL), as well as cytotoxicity against the human HeLa cancer cell line (IC50: 3.0-9.0 µM). In addition, compounds 1 and 5 displayed significant activity against several Mycobacterium tuberculosis clinical isolates (MIC: 4-32 µg/mL).

Iridoid glycosides from the fruits of Cornus officinalis.

Four new iridoid glycosides named cornusphenosides A-D (1-4) were isolated from an ethanol extract of the fruits of Cornus officinalis (shan zhu yu). The structures of these compounds were elucidated on the basis of spectroscopic data (UV, IR, HRESIMS, and 1D and 2D NMR) and chemical evidence. The neuroprotective effects of compounds 1-4 were also assessed in vitro.

A new cytotoxic 12-membered macrolactone from the endophytic fungus Exserohilum rostratum LPC-001.

A new oxacyclododecindione-type macrolactone, (13R,14S,15R)-13-hydroxy-14-deoxyoxacyclododecindione (1), has been obtained from the solid cultures of the fungus Exserohilum rostratum, a fungal strain endophytic in Gymnadenia conopsea. Its structure, including the absolute configuration, was extensively established by 1D and 2D NMR data, the modified Mosher method, and a combination of experimental and theoretically calculated electronic circular dichroism (ECD) spectra. Compound 1 showed weak selective cytotoxicity against the A549 lung cell line with an IC50 value of 9.2 µM.

Two new terpenoid ester glycosides from the twigs of Litsea cubeba.

A new sesquiterpenoid ester glycoside (1) and a new monoterpenoid ester glycoside (2) have been isolated from an ethanol extract of the twigs of Litsea cubeba. Their structures were elucidated by extensive 1D- and 2D-NMR experiments, and the absolute configurations were determined by chemical methods, specific rotation, and a combination of experimental and theoretically calculated electronic circular dichroism spectra. Compound 1 exhibited selective cytotoxicity against A549 and HCT-8 cell lines with the IC50 values of 8.9 and 9.6 µM, respectively.

Four new monacolin analogs from Monascus purpureus-fermented rice.

Four new monacolin analogs, monacolin T (1), monacolin U (2) 6a-O-methyl-4,6-dihydromonacolin L (3), and 6a-O-ethyl-4,6-dihydromonacolin L (4) were isolated from the ethanolic extract of Monascus purpureus-fermented rice. Their structures were determined by a combination of 1D, 2D NMR experiments (1H-1HCOSY, HSQC, HMBC, and ROESY), and mass spectrometry. In vitro cytotoxic assay, all compounds were inactive at the concentration of 10 µM.

Monascustin, an Unusual γ-Lactam from Red Yeast Rice.

Monascustin (1), an unusual γ-lactam, was isolated from an ethanol extract of the Monascus purpureus fermented rice. Its structure including the absolute configuration was determined by spectroscopic data analysis and confirmed by X-ray crystallography. A plausible biosynthetic pathway is discussed on the basis of amino acid derivatization. Compound 1 showed inhibitory activity against histone deacetylase 1.

Design, Recombinant Fusion Expression and Biological Evaluation of Vasoactive Intestinal Peptide Analogue as Novel Antimicrobial Agent.

Antimicrobial peptides represent an emerging category of therapeutic agents with remarkable structural and functional diversity. Modified vasoactive intestinal peptide (VIP) (VIP analogue 8 with amino acid sequence "FTANYTRLRRQLAVRRYLAAILGRR") without haemolytic activity and cytotoxicity displayed enhanced antimicrobial activities against Staphylococcus aureus (S. aureus) ATCC 25923 and Escherichia coli (E. coli) ATCC 25922 than parent VIP even in the presence of 180 mM NaCl or 50 mM MgCl2, or in the range of pH 4-10. VIP analogue 8 was expressed as fusion protein thioredoxin (Trx)-VIP8 in E. coli BL21(DE) at a yield of 45.67 mg/L. The minimum inhibitory concentration (MIC) of the recombinant VIP analogue 8 against S. aureus ATCC 25923 and E. coli ATCC 25922 were 2 µM. These findings suggest that VIP analogue 8 is a promising candidate for application as a new and safe antimicrobial agent.

Four new taraxastane-type triterpenoic acids from Cirsium setosum.

Four new taraxastane-type triterpenoids acids 3ß,22α-dihydroxy-20-taraxasten-30-oic acid (1), 3ß-hydroxy-22-oxo-20-taraxasten-30-oic acid (2), 3-oxo-22α-hydroxy-20- taraxasten-30-oic acid (3), and 3ß,19ß-dihydroxy-20-taraxasten-30-oic acid (4) were isolated and characterized from Cirsium setosum (Willd.) MB. Their structures were determined by the combination of 1D and 2D NMR experiments ((1)H-(1)HCOSY, HSQC, HMBC and ROESY) and mass spectrometry. Compound 2 exhibited potent selective cytotoxicity against human ovarian cancer cell line A2780 with an IC50 value of 3.9 µM.