Isolation and Characterization of Antimicrobial Metabolites from the Sophora tonkinensis-Associated Fungus Penicillium sp. GDGJ-N37.

Chemical investigation of Penicillium sp. GDGJ-N37, a Sophora tonkinensis-associated fungus, yielded two new azaphilone derivatives, N-isoamylsclerotiorinamine (1) and 7-methoxyl-N-isoamylsclerotiorinamine (2), and four known azaphilones (3-6), together with two new chromone derivatives, penithochromones X and Y (7 and 8). Their structures were elucidated based on spectroscopic data, CD spectrum, and semi-synthesis. Sclerotioramine (3) showed significant antibacterial activities against B. subtilis and S. dysentery, and it also showed most potent anti-plant pathogenic fungi activities against P. theae, C. miyabeanus, and E. turcicum.

Triterpenoids from the Leaves of Cyclocarya paliurus and Their Glucose Uptake Activity in 3T3-L1 Adipocytes.

Four new dammarane triterpenoid saponins cypaliurusides Z1-Z4 (1-4) and eight known analogs (5-12) were isolated from the leaves of Cyclocarya paliurus. The structures of the isolated compounds were determined using a comprehensive analysis of 1D and 2D NMR and HRESIMS data. The docking study demonstrated that compound 10 strongly bonded with PTP1B (a potential drug target for the treatment of type-II diabetes and obesity), hydrogen bonds, and hydrophobic interactions, verifying the importance of sugar unit. The effects of the isolates on insulin-stimulated glucose uptake in 3T3-L1 adipocytes were evaluated and three dammarane triterpenoid saponins (6, 7 and 10) were found to enhance insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Furthermore, compounds 6, 7, and 10 exhibited potent abilities to promote insulin-stimulated glucose uptake in 3T3-L1 adipocytes in a dose-dependent manner. Thus, the abundant dammarane triterpenoid saponins from C. paliurus leaves exhibited stimulatory effects on glucose uptake with application potential as a antidiabetic treatment.

α-Glucosidase inhibitory and anti-inflammatory activities of dammarane triterpenoids from the leaves of Cyclocarya paliurus.

Diabetes mellitus is caused by chronic inflammation and affects millions of people worldwide. Cyclocarya paliurus leaves have been widely used in traditional folk tea as a remedy for diabetes, but the antidiabetic constituents remain to be further studied. The α-glucosidase inhibitory and anti-inflammatory activities were examined to evaluate their effects on diabetes mellitus, and bioassay-guided separation of C. paliurus leaves led to the identification of twenty dammarane saponins, including eleven new dammarane saponins (1-11). The structures of the isolates were elucidated by spectroscopic methods. Bioactivity assay results showed that compounds 1 and 2 strongly inhibited α-glucosidase activity, with IC50 values ranging from 257.74 µM, 282.23 µM, and strongly inhibited the release of NO, with IC50 values of 9.10 µM, 9.02 µM. Moreover, compound 2 significantly downregulated the mRNA expression of iNOS, COX-2, IL-1ß, NF-κB, IL-6 and TNF-α in LPS-mediated RAW 264.7 cells and markedly suppressed the protein expression of iNOS, NF-κB/p65, and COX-2. Dammarane glucoside 2 exhibited the strongest α-glucosidase inhibitory and anti-inflammatory activities. In addition, the structure-activity relationships (SARs) of the dammarane saponins were investigated. In summary, C. paliurus leaves showed marked α-glucosidase inhibitory and anti-inflammatory activities, and dammarane saponins are responsible for regulating α-glucosidase, inflammatory mediators, and mRNA and the protein expression of proinflammatory cytokines, which could be meaningful for discovering new antidiabetic agents.

Polyketide Derivatives, Guhypoxylonols A-D from a Mangrove Endophytic Fungus Aspergillus sp. GXNU-Y45 That Inhibit Nitric Oxide Production.

Four undescribed compounds, guhypoxylonols A (1), B (2), C (3), and D (4), were isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y45, together with seven previously reported metabolites. The structures of 1-4 were elucidated based on analysis of HRESIMS and NMR spectroscopic data. The absolute configurations of the stereogenic carbons in 1-3 were established through a combination of spectroscopic data and electronic circular dichroism (ECD). Compounds 1-11 were evaluated for their anti-inflammatory activity. Compounds 1, 3, 4, and 6 showed an inhibitory activity against the production of nitric oxide (NO), with the IC50 values of 14.42 ± 0.11, 18.03 ± 0.14, 16.66 ± 0.21, and 21.05 ± 0.13 µM, respectively.

Cytotoxic Activity and Related Mechanisms of Prenylflavonoids Isolated from Mallotus conspurcatus Croizat.

Five prenylflavonoids, 6-prenylnaringenin (1), 8-prenylnaringenin (2), 7-O-methyl-8-prenylnaringenin (3), 7-O-methyl-6-prenylnaringenin (4), and 4'-O-methyl-6-prenylnaringenin (5), were isolated from the traditional herb Mallotus conspurcatus Croizat (Euphorbiaceae). Compounds 1-5 revealed cytotoxic activity against cervical cancer (HeLa) cells with IC50 values ranging from 10.08 to 60.16 µm by MTT method, and interestingly, these prenylflavonoids were less toxic to normal HL-7702 cells. Furthermore, compounds 1 and 5 could inhibit the c-myc expression and telomerase activity and cause mitochondrial dysfunction. These findings might contribute to a better understanding of the biological activities of prenylflavonoids and lay the foundation for further studies on the cytotoxic activity of natural products isolated from M. conspurcatus.

Structural Characterization and Assessment of the Cytotoxicity of 2,3-Dihydro-1H-indene Derivatives and Coumarin Glucosides from the Bark of Streblus indicus.

A pair of enantiomers and a pair of 2,3-dihydro-1H-indene epimers, rac-indidene A (rac-1), indidenes B and C (2, 3); four new coumarin glucosides (4-7); and four known coumarin glucosides (8-11) were isolated from the bark of Streblus indicus (Bur.) Corner. The structures of 1-11 were defined by physical data analyses, including MS, NMR, and single-crystal X-ray diffraction. The absolute configurations of the 2,3-dihydro-1H-indene derivatives were defined via experimental and calculated ECD data. rac-Indidene A and indidenes B and C showed inhibitory activity against A549 and MCF-7 tumor cells with IC50 values in the range of 2.2 ± 0.1 to 7.2 ± 0.9 µM.

Nigrodiquinone A, a Hydroanthraquinone Dimer Containing a Rare C-9-C-7' Linkage from a Zoanthid-Derived Nigrospora sp. Fungus.

One new hydroanthraquinone dimer with a rare C-9-C-7' linkage, nigrodiquinone A (1), and four known anthraquinone monomers 2-5, were isolated from a fungus Nigrospora sp. obtained from the zoanthid Palythoa haddoni collected in the South China Sea. The structure of 1 was established through extensive NMR spectroscopy, and the absolute configuration was elucidated by comparing computed electronic circular dichroism (ECD) and optical rotations (OR) with experimental results. All the compounds were evaluated for antiviral activity, and 1 was also evaluated for antibacterial activity. Compound 4 displayed mild antiviral activity against coxsackie virus (Cox-B3) with the IC50 value of 93.7 µM, and 5 showed an IC50 value of 74.0 µM against respiratory syncytial virus (RSV).

Tandem mass spectrometric fragmentation behavior of lignans, flavonoids and triterpenoids in Streblus asper.

RATIONALE: An unambiguous identification of compounds can be achieved by comparison of known fragmentation patterns. While the literature about fragmentation mechanisms of lignans, flavonoids and triterpenoids is few. So the present study analyses the fragmentation mechanisms of these compounds isolated from Streblus asper. METHODS: Electrospray ionization ion trap mass spectrometry (ESI-ITMS) and atmospheric pressure chemical ionization ion trap mass spectrometry (APCI-ITMS) were used to obtain the MS(n) spectra of the compounds. By analyzing the differences between the ions, the fragmentation mechanisms of these compounds were explored. RESULTS: Of the 29 compounds detected, 17, 7, and 5 were lignans, flavonoids and triterpenoids, respectively. The majority of lignans were found to give [M - H](-) ions of sufficient abundance for MS(n) analyses. The flavonoids were prone to the loss of CO and H2O. The triterpenoids always lost one formic acid molecule and two hydrogens, or one H2O from [M - H](-) to form the most abundant product ion in the MS(n) spectrum. CONCLUSIONS: ESI/APCI-ITMS were demonstrated to be fast, effective and practical tools to characterize the structures of flavonoids, triterpenoids and lignans. Results of the present study can help identify the analogous constituents by analyzing their MS(n) spectra.

Anti-hepatitis B virus lignans from the root of Streblus asper.

Four new lignans, strebluslignanol F (1), (7'R,8'S,7″R,8″S)-erythro-strebluslignanol G (2), isomagnaldehyde (3) and isostrebluslignanaldehyde (4), along with 12 known lignans (5-16) were isolated from the ethyl acetate-soluble part of MeOH extract of the root of Streblus asper. Their structures were elucidated through various spectroscopic methods, including 1D NMR ((1)H NMR, (13)C NMR), 2D NMR (HMQC, HMBC and NOESY) and HRMS. The stereochemistry at the chiral centers was determined using CD spectra, as well as analyses of coupling constants and optical rotation data. The isolated lignans were evaluated for their anti-HBV activities in vitro using the HBV transfected HepG2.2.15 cell line. The most active lignans, (7'R,8'S,7″R,8″S)-erythro-strebluslignanol G, magnolol, isomagnolol and isolariciresinol, exhibited significant anti-HBV activities with IC50 values of 1.58, 2.03, 10.34 and 3.67 µM, respectively, for HBsAg with no cytotoxicity, and of 3.24, 3.76, 8.83 and 14.67 µM, respectively, for HBeAg with no cytotoxicity. (7'R,8'S,7″R,8″S)-erythro-Strebluslignanol G and magnolol showed significant anti-HBV activities to inhibit the replication of HBV DNA with the IC50 values of 9.02 and 8.67 µM, respectively.

A new lactone from mangrove endophytic fungus Aspergillus sp. GXNU-A9.

A new lactone, asperlactone A (1), and four known lactone derivatives 2-5 were isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-A9. Their structures were elucidated based on high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) datum, extensive nuclear magnetic resonance (NMR) spectroscopic analysis, and comparison with literature data. The structure of 1 was further confirmed by single-crystal X-ray diffraction analysis, and the absolute configuration of 1 was established. Compounds 1-5 were evaluated for their anti-inflammatory activities against nitric oxide (NO) production, and compounds 1-5 showed moderate inhibitory activities with IC50 values ranging from 15.87 to 30.48 µM.

Megastigmane glycosides from Streblus ilicifolius (S.Vidal) Corner and their anti-inflammatory activity.

Twelve undescribed megastigmane glycosides, streilicifolosides A-L (1-12), together with 8 known analogues (13-21) were isolated from the leaves of Streblus ilicifolius (S.Vidal) Corner. Their plannar structures were elucidated using extensive NMR spectroscopic methods (1D and 2D-NMR spectroscopy), and HRESIMS spectroscopic data analyses. The absolute configurations of the undescribed compounds were determined by the glucose-induced shift-trend, calculated and experimental circular dichroism spectroscopy. All the compounds were tested for inhibitory effects on the production of NO in LPS-treated RAW264.7 cells, and streilicifoloside E and platanionoside D exhibited potent anti-inflammatory activity comparable to that of the positive control, with IC50 values of 26.33 and 21.84 µM, respectively. Furthermore, these two compounds markedly decreased the secretion of PGE2 and TNF-α and inhibited the expression of COX‒2, iNOS and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner. In addition, the structure-activity relationships of the isolates were also discussed. The results suggest that streilicifoloside E and platanionoside D could be used as potential candidates for the development of new anti-inflammatory agents.

Diagnostic value of upper airway morphological data based on CT volume scanning combined with clinical indexes in children with obstructive sleep apnea syndrome.

Background and purpose: Early diagnosis is important for treatment and prognosis of obstructive sleep apnea (OSA)in children. Polysomnography (PSG) is the gold standard for the diagnosis of OSA. However, due to various reasons, such as inconvenient implementation, less equipped in primary medical institutions, etc., it is less used in children, especially in young children. This study aims to establish a new diagnostic method with imaging data of upper airway and clinical signs and symptoms. Methods: In this retrospective study, clinical and imaging data were collected from children ≤10 years old who underwent nasopharynx CT scan(low-dose protocol)from February 2019 to June 2020,including 25 children with OSA and 105 non-OSA. The information of the upper airway (A-line; N-line; nasal gap; upper airway volume; upper and lower diameter, left and right diameter and cross-sectional area of the narrowest part of the upper airway) were measured in transaxial, coronal, and sagittal images. The diagnosis of OSA and adenoid size were given according to the guidelines and consensus of imaging experts. The information of clinical signs, symptoms, and others were obtained from medical records. According to the weight of each index on OSA, the indexes with statistical significance were screened out, then were scored and summed up. ROC analysis was performed with the sum as the test variable and OSA as the status variable to evaluate the diagnostic efficacy on OSA. Results: The AUC of the summed scores (ANMAH score) of upper airway morphology and clinical index for the diagnosis of OSA was 0.984 (95% CI 0.964-1.000). When sum = 7 was used as the threshold (participants with sum>7 were considered to have OSA), the Youden's index reached its maximum at which point the sensitivity was 88.0%, the specificity was 98.1%, and the accuracy was 96.2%. Conclusion: The morphological data of the upper airway based on CT volume scan images combined with clinical indices have high diagnostic value for OSA in children; CT volume scanning plays a great guiding role in the selection of treatment scheme of OSA. It is a convenient, accurate and informative diagnostic method with a great help to improving prognosis. Highlights: - Early diagnosis of OSA in children is very important for the treatment.- However, the traditional diagnostic gold-standard PSG is difficult to implement.- This study aims to explore convenient and reliable diagnostic methods for children.- A new diagnostic model was established combining CT with signs and symptoms.- The diagnostic method in this study is highly effective, informative, and convenient.

Antibacterial bisabolane-type sesquiterpenoids from the sponge-derived fungus Aspergillus sp.

Four new bisabolane-type sesquiterpenoids, aspergiterpenoid A (1), (-)-sydonol (2), (-)-sydonic acid (3), and (-)-5-(hydroxymethyl)-2-(2',6',6'-trimethyltetrahydro-2H- pyran-2-yl)phenol (4) together with one known fungal metabolite (5) were isolated from the fermentation broth of a marine-derived fungus Aspergillus sp., which was isolated from the sponge Xestospongia testudinaria collected from the South China Sea. Four of them (1-4) are optically active compounds. Their structures and absolute configurations were elucidated by using NMR spectroscopic techniques and mass spectrometric analysis, and by comparing their optical rotations with those related known analogues. Compounds 1-5 showed selective antibacterial activity against eight bacterial strains with the MIC (minimum inhibiting concentrations) values between 1.25 and 20.0 µM. The cytotoxic, antifouling, and acetylcholinesterase inhibitory activities of these compounds were also examined.

A new sesquiterpene from mangrove endophytic fungus Aspergillus sp. GXNU-MA1.

A new sesquiterpene, gxsespene A (1), and four known sesquiterpene derivatives 2-5 were isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-MA1. Their structures were elucidated based on high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) datum, extensive nuclear magnetic resonance (NMR) spectroscopic analysis, and comparison with literature data. The structure of 1 was further confirmed by single-crystal X-ray diffraction analysis, and the absolute configuration of 1 was established. Compounds 1-5 were evaluated for their anti-inflammatory activities against the nitric oxide (NO) production, and compounds 1-5 showed moderate inhibitory activities with IC50 values ranging from 16.15 to 27.08 µM.

A new depsidone derivative from mangrove endophytic fungus Aspergillus sp. GXNU-A9.

A new tetracyclic depsidone derivative, guanxidone A (1), together with three known metabolites 2-4, was isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-A9. The structure of compound 1 was established by HR-ESI-MS, 1 D and 2 D NMR data, as well as by comparison with literature data. Compounds 1-4 were evaluated for their anti-inflammatory effects on the production of the nitric oxide (NO), and compound 1 significantly reduced the production of NO in lipopolysaccharide (LPS)-stimulated cells with IC50 value of 8.22 µM.

Cytotoxic cardiac glycosides from the root of Streblus asper.

Bioassay-guided separation of the root of Streblus asper led to the identification of six undescribed cardiac glycosides, including a rare cardiac glycoside dimer, along with twelve previously reported analogues. Their structures were determined on the basis of analyses of spectroscopic methods (1D and 2D-NMR spectroscopy), high-resolution electrospray ionization mass spectrometry (HRESIMS), circular dichroism (CD), and comparison of their spectroscopic data with previously reported data. Regarding their cytotoxic activities, microculture tetrazolium assays showed that all isolated cardiac glycosides strongly inhibited MCC-803, T24, SKOV-3, HepG2, Wi-38, and A549 cancer cell lines, with IC50 values ranging from 0.075 µM to 0.752 µM. One cardiac glycoside, a rare cardiac glycoside dimer, exhibited the strongest activity against the six cancer cell lines, with IC50 values ranging from 0.075 µM to 0.214 µM. In addition, the structure-activity relationships (SARs) of cardiac glycosides were investigated. In summary, S. asper showed marked cytotoxicity to several cancer cell lines, which could be meaningful for discovering new anticancer agents.

Cycloaspeptide H, a cyclopentapeptide from the endophytic fungus Penicillium virgatum.

One new cyclopentapeptide, cycloaspeptide H (1), featuring a serine residue, along with seven known compounds (2-8), was isolated from the endophytic fungus Penicillium virgatum GDGJ-227. The planar structure of 1 was elucidated by a comprehensive analysis of NMR and MS spectroscopic spectra, and the absolute configuration was determined by single-crystal X-ray diffraction (Cu Kα) analysis. Compounds 7 and 8 displayed antibacterial activities against Bacillus subtilis and Enterobacter aerogenes with MIC values ranging from 12.5 to 50 µg/mL.

Two new cytochalasins from the endophytic fungus Xylaria sp. GDGJ-77B.

Two new open-chain cytochalasins, xylarchalasins A and B (1 and 2), together with six known analogues (3-8), were isolated from the endophytic fungus Xylaria sp. GDGJ-77B from the Chinese medicinal plant Sophora tonkinensis. Their structures were elucidated on the basis of comprehensive spectroscopic analysis. Compound 2 displayed moderate antibacterial activities against Bacillus subtilis and Escherichia coli with MIC values of 25 and 12.5 µg/mL, respectively.

Three new andrastin derivatives from the endophytic fungus Penicillium vulpinum.

Three new andrastin derivatives, 10-formyl andrastone A (1), 10-demethylated andrastone A (2) and andrastin G (3), together with four known andrastin analogues (4-7) were isolated from an endophytic fungus Penicillium vulpinum. Their structures were determined by 1 D, 2 D NMR, and the absolute configurations were further determined by experimental and calculated ECD spectra. Compound 5 exhibited significant antibacterial activity against Bacillus paratyphosus B with an MIC value of 6.25 µg·mL-1. Compounds 2 and 6 showed remarkable inhibitory activities against Bacillus megaterium with the MIC value of 6.25 µg·mL-1, respectively.

Two new phthalide derivatives from the endophytic fungus Penicillium vulpinum isolated from Sophora tonkinensis.

Two new phthalide derivatives, (-)-3-carboxypropyl-7-hydroxyphthalide (1) and (-)-3-carboxypropyl-7-hydroxyphthalide methyl ester (2), were isolated from the endophytic fungus Penicillium vulpinum isolated from the Chinese medicinal plant Sophora tonkinensis. Their structures were elucidated using spectroscopic methods, mainly on 1D and 2D NMR. Compound 1 exhibited medium antibacterial activities against Bacillus subtilis, Shigella dysenteriae and Enterobacter areogenes with MIC values of 12.5-25 µg/mL, and 2 showed a medium inhibition to E. areogenes with MIC value of 12.5 µg/mL.