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.

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.

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.

Cytochalasins from endophytic Diaporthe sp. GDG-118.

The plant Sophora tonkinensis, possessed a range of active compounds, was traditionally used in the medicine of Chinese minorities. Endophytic fungi were isolated from this plant, of which the fungus Diaporthe sp. GDG-118 was fermented and extracted with methanol. The extract was screened by antifungal and antibacterial assays leading to the discovery of two new 21-acetoxycytochalasins (1-2) and five known cytochalasins (3-7). These two new compounds were elucidated by spectroscopic analyses, and further their absolute configurations were determined by the X-ray of compound 3 and comparing their experimental CD spectra. The antibacterial and antifungal effects of these compounds were evaluated. Compound 2 showed significant inhibitory activity against Bacillus anthraci and Escherichia coli with MIC value of 12.5 µg/mL, and 7 showed strong antifungal activity against Alternaria oleracea, Pestalotiopsis theae and Colletotrichum capsici with MIC values of 3.125, 1.56 and 1.56 µg/mL, respectively.

Bioactivity-guided isolation of anti-inflammatory constituents from the bark of Streblus zeylanicus.

Based on anti-inflammatory activity to evaluate the effects to the release of NO, bio-assay guided separation of the bark of Streblus zeylanicus led to identify fifteen compounds, including four new terpenes (1, 2, 9, and 10), one new pentanoid glycoside (12), one new rumenic ester (13), together with nine known compounds (3-8, 11, 14, and 15). Their structures were elucidated using extensive NMR and HRESIMS spectroscopic data analyses. The stereochemistry of compound 10 was established by comparing the calculated and experimental ECD spectroscopic data. Compounds 1 and 2 showed moderate inhibition on nitric oxide (NO) production, with IC50 values of 10.21 µM and 15.53 µM, respectively.

3,4-seco-Dammarane Triterpenoid Saponins with Anti-Inflammatory Activity Isolated from the Leaves of Cyclocarya paliurus.

Cyclocarya paliurus is commonly used for the prevention and treatment of hypertension, diabetes, and inflammation in South China. Although research on the anti-inflammatory effects of C. paliurus leaves has been reported, no active anti-inflammatory compounds have been identified. In the present study, RAW 264.7 cells were used to establish a bioactivity-guided identification model to verify the inhibitory effects of C. paliurus leaves on inflammation and identify the anti-inflammatory constituents. The active fraction was isolated to yield 18 dammarane triterpenoid saponins, including 11 new 3,4-seco-dammarane triterpenoid saponins (1-11), the structures of which were identified on the basis of analyses of nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) and comparison with literature data. Compounds 7, 8, 10, and 11 showed strong inhibition on nitric oxide (NO) productions, with IC50 values ranging from 8.23 to 11.23 µM. These four compounds significantly decreased the secretion of tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), and interleukin 6 (IL-6) in lipopolysaccharide-activated RAW 264.7 cells. Furthermore, compound 7 decreased the expression of the proteins cyclooxygenase-2 (COX-2), inducible nitric-oxide synthase (iNOS), and nuclear factor kappa-B (NF-κB/p65). In addition, the structure-activity relationships of the isolates were investigated. The results suggest that 3,4-seco-dammarane triterpenoid saponins may be used as potential anti-inflammatory drugs and warrant further investigation.

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.

Eremophilane sesquiterpenes from the endophytic fungus Xylaria sp. GDG-102.

A new eremophilane sesquiterpene, xylareremophil (1), together with five known eremophilanes, 1α,10α-epoxy-3α-hydroxyeremophil-7(11)-en-12,8ß-olide (2), 1,10α,13-trihydroxyeremophil-7(11)-en-12,8-olide (3), 1α,10α-epoxy-13-hydroxyeremophil-7(11)-en-12,8ß-olide (4), mairetolides B (5) and G (6) were isolated from the endophytic fungus Xylaria sp. GDG-102 cultured from Sophora tonkinensis. Their structures were elucidated on the basis of spectroscopic data analysis. The absolute configurations of 1 was determined by comparing computed electronic circular dichroism (ECD) and optical rotation (OR) with experimental results. Compounds 1, 5 and 6 showed antibacterial activities against Proteus vulgaris, Micrococcus luteus, Micrococcus lysodeikticus and Bacillus subtilis with MIC values of 25-100 µg/mL.

Discovery of anti-inflammatory terpenoids from Mallotus conspurcatus croizat.

ETHNOPHARMACOLOGICAL RELEVANCE: Mallotus conspurcatus croizat (Euphorbiaceae), a plant native to Jinxiu in Guangxi, is popularly used in folk medicine to treat pelvic inflammatory disease. The anti-inflammatory activities of the compounds obtained from M. conspurcatus root were evaluated in this study. AIM OF THE STUDY: This study explored the major anti-inflammatory components of this plant. MATERIALS AND METHODS: The ethyl acetate fraction of the ethanol extract from M. conspurcatus was separated using chromatographic techniques. The structures of the isolates were elucidated from NMR, MS and X-ray data as well as from ECD. The anti-inflammatory activities of the isolates from M. conspurcatus were evaluated using LPS-stimulated RAW 264.7 cell models. The production of NO, TNF-α and PGE-2 was determined by ELISA and Griess tests. The expression levels of COX-2, NF-κB/p65 and iNOS were measured by western blotting. RESULTS: Two new diterpenoids, malloconspur A (1) and malloconspur B (2), and sixteen known terpenoids (3-18) were identified by comprehensive spectroscopic analyses and comparison with literature data. Malloconspur B (2) and 17-hydroxycleistantha-12,15-dien-3-one (3) substantially inhibited the release of NO with IC50 values of 10.47 µM and 9.32 µM, respectively. Compounds 1, 2 and 3 markedly decreased the secretion of PGE2 and TNF-α (P < 0.01) by LPS-induced RAW264.7 cells. Compounds 2 and 3 markedly decreased iNOS, NF-κB/p65 and COX-2 protein expression. CONCLUSIONS: Our identification of these diterpenoids provides strong evidence for the use of M. conspurcatus among the Yao people as a medicinal plant for the treatment of inflammation. The dramatic differences in the chemical structures of the active diterpenoids of this plant from those on the market suggest these compounds have potential as anti-inflammatory lead compounds for follow-up research.

Anti-inflammatory lignans and phenylethanoid glycosides from the root of Isodon ternifolius (D.Don) Kudô.

Five undescribed lignans, three undescribed phenylethanoid glycosides and eight known compounds were isolated from the root of Isodon ternifolius (D.Don) Kudô (Lamiaceae). The structures of all of the isolated constituents were characterized by physical data analyses including NMR, MS and ECD. The anti-inflammatory activities of the isolates were evaluated based on their ability to inhibit NO, PGE2 and TNF-α production in LPS-induced RAW 264.7 macrophage cells. Six phenyl-naphthalene lignans, ternifoliuslignan A, ternifoliuslignan B, ternifoliuslignan C, ternifoliuslignan D, ternifoliuslignan E and 3-carboxy-6,7-dihydroxy-1-(3',4'-dihydroxyphenyl) -naphthalene, can substantially inhibit the release of NO with IC50 values in the range of 9.98-29.14 µM, which are better than the positive reference. These phenyl-naphthalene lignans could markedly decrease the secretions of PGE2 and TNF-α in LPS-induced RAW264.7 cells. Ternifoliuslignan C and ternifoliuslignan D decreased iNOS, COX-2 and NF-κB/p65 protein expression. A preliminary structure-activity relationship among the phenyl-naphthalene lignans for the anti-inflammatory activity was discussed.

Two new coumarins from the bark of Streblus indicus (Bur.) Corner.

Two new coumarins 7-O-(6-O-(5-O-3,4,5-tri-methoxycinnamate-ß-d-apiofuranosyl-ß-d-glucopyranosyl)-6-methoxy coumarin (1) and 7-O-(6-O-(4-(2-hydroxy-1-hydroxymethyl-ethoxy)-3-methoxy-cinnamyl)-ß-d-glucopyranosyl)-6-methoxy coumarin (2), along with 10 known metabolites, were isolated from the bark of Streblus indicus, their structures were identified by comparison of experimental and published spectroscopic data. (S)-marmesinin (6) and scoparone (7) exhibited moderate antimicrobial activity in vitro against Staphylococcus aureus strain with the MIC values of 62.5 and 125.0 µg/mL, respectively. Betulinic acid showed inhibitory activity in vitro against MCF-7 cell with IC50 value of 9.5 ± 0.1 µM.

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.

[Changes of AFP and beta-hCG in testicular tumors analyzed by a function method].

OBJECTIVE: To establish a new function method for the analysis of a-fetoprotein (AFP) and beta-hCG in testicular tumors. METHODS: We reexamined the serum levels of AFP and beta-hCG after radical orchiectomy, and calculated the measured coordinate, with the abscissa representing the number of the half-lives of tumor markers, and the ordinate representing the measured value of tumor markers. Referring to the measured value of tumor markers before surgery as a, the number of half-lives as x, and their theoretical value over a period of x elimination half-lives as y (logarithm to the base 2 of y), we calculated the predicted coordinate according to the formula y = log2(a/2x) ==> x + y = log2a (function 1). Then we assessed tumor residue and metastasis by analyzing the relationship between the measured and predicted coordinates. RESULTS: The pathological examination of case 1 revealed a germ cell tumor of a mixed histological pattern of syncytiotrophoblast and yolk sac tumor. The measured coordinates of AFP and beta-hCG were (2.22, 6.21) and (10, 8.38), and the predicted coordinates (2.22, 6.34) and (10, 4.41) , indicating the elimination of the yolk sac tumor and metastasis of the syncytiotrophoblast tumor. Case 2 demonstrated the mixed pathological nature of teratocarcinoma and yolk sac tumor. The measured coordinates of AFP and beta-hCG were (2.67, -1.03) and (12, -3.32), and the predicted coordinates (2.67, 1.41) and (12, -5.80). But the review times of AFP and beta-hCG were out of the effective range of half-lives, with the measured values below the normal, which suggested no tumor residue or metastasis. Case 3 was found to be embryonal carcinoma. The measured coordinate of AFP was (0.22, 9.25) , and the predicted coordinate (0.22, 9.55) , indicating the elimination of tumor. CONCLUSION: The change of the tumor markers predicted by the function method coincided with the natural course of disease in the three cases. The coincidence of the measured with the predicted coordinate after radical orchiectomy indicates no metastasis, while their disagreement suggests possible residue and metastasis of the tumor.