Lyonensinols A - C, 24-Norursane-Type Triterpenoids from the Twigs and Leaves of Lyonia doyonensis and Their Potential Anti-inflammatory and PTP1B Inhibitory Activities.

Lyonia doyonensis is a deciduous shrub native to high-altitude regions of Asia. So far, there is no report on any chemical and biological properties of L. doyonensis. An EtOH extract of L. doyonensis twigs and leaves showed inhibitory activities on protein tyrosine phosphatase 1B and lipopolysaccharide-induced inflammation in BV-2 microglial cells. A phytochemical investigation of this extract led to the isolation of a, so far only ambiguously described, 24-norursane-type triterpenoid, now named lyonensinol A (1: ), along with its two new derivatives, lyonensinols B and C (2: and 3: ), and six known triterpenoids (4 - 9: ). Their structures were elucidated by detailed analysis of spectroscopic data. A combination of chemical conversions, electronic circular dichroism, and Mo2(OAc)4-induced electronic circular dichroism was used to confirm their absolute configurations. Lyonensinols B (2: ) and C (3: ) represent the first examples of norursane-type triterpenoids acylated with a p-coumaroyl moiety. The potential anti-inflammatory and protein tyrosine phosphatase 1B inhibitory activities of all the isolates were evaluated. Compounds 3, 7: , and 8: at 10 µM showed potent inhibitory activities on lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, with nitric oxide levels decreasing to 31.5, 41.9, and 27.1%, respectively, while compounds 3, 4, 7: , and 8: exhibited notable inhibitory activities against protein tyrosine phosphatase 1B, with IC50 values ranging from 1.7 to 18.2 µM. Interestingly, compounds 3: and 8: , bearing a C-3 trans-p-coumaroyl group, showed not only more potent anti-inflammatory effects, but also exhibited stronger protein tyrosine phosphatase 1B inhibition than their respective stereoisomers (2: and 7: ) with a cis-p-coumaroyl group.

Phenylpropanoid and Iridoid Glucosides from the Whole Plant of Hemiphragma heterophyllum and Their alpha-Glucosidase Inhibitory Activities.

Three phenylpropanoid glucosides (1:  - 3: ) and one iridoid glucoside (11: ), together with eleven known glucosides, were isolated from the ethanol extract of the whole plant of Hemiphragma heterophyllum. Their structures were elucidated by means of 1D and 2D NMR spectroscopy, HRMS, and chemical methods. All compounds except 11: and 13:  - 15: showed varying degrees of α-glucosidase inhibitory activity. Compounds 5, 9: , and 12: were marginally active in the bioassay, while compounds 1:  - 4: , 6:  - 8: , and 10: exhibited appreciable inhibitory activity with an IC50 value of 33.6 ~ 83.1 µM, which was much lower than that of the positive control acarbose (IC50 = 310.8 µM).

α-Glucosidase Inhibitory and Anti-Inflammatory Coumestans from the Roots of Dolichos trilobus.

Four new coumestans dolichosins A - D (1: -4: ) were isolated from the roots of Dolichos trilobus, together with four known compounds: isosojagol (5: ), phaseol (6: ), psoralidin (7: ), and 4″,5″-dehydroisopsoralidin (8: ). Their structures were elucidated on the basis of spectroscopic data interpretation, mass spectrometric analyses, and the comparison with literature data of related compounds. The anti-inflammatory activity of these compounds (1: -8: ) was evaluated through the inhibition of nitric oxide production in lipopolysaccharide-activated murine macrophage RAW 264.7 cells, in which compounds 1: and 6: displayed moderate inhibitory activity and no cytotoxic effects. In a α-glucosidase inhibitory assay, compounds 1: and 5: -8: exhibited appreciable inhibition on α-glucosidase. Especially compounds 1, 7: , and 8: showed IC50 values lower than 20.0 µM.

[Chemical constituents of Cassia siamea].

A total of ten compounds were isolated from the 90% Et OH extract of Cassia siamea by using various chormatographic techniques,and their structures were established as( 2' S)-2-( propan-2'-ol)-5,7-dihydroxy-benzopyran-4-one( 1),chrobisiamone( 2), 2-( 2'-hydroxypropyl)-5-methyl-7-hydroxychromone( 3), 2,5-dimethyl-7-hydroxychromone( 4), 2-methyl-5-acetonyl-7-hydroxychromone( 5),3-O-methylquercetin( 6),3,5,7,3',4'-pentahydroxyflavonone( 7),luteolin-5,3'-dimethylether( 8),4-( trans)-acetul-3,6,8-trihydroxy-3-methyl-dihydronapht halenone( 9) and 6-hydroxymellein( 10) based on the spectroscopic data.Compound 1 was a new compound,and 3,4,6,8 were isolated from this plant for the first time.

Adipsin inhibits Irak2 mitochondrial translocation and improves fatty acid ß-oxidation to alleviate diabetic cardiomyopathy.

BACKGROUND: Diabetic cardiomyopathy (DCM) causes the myocardium to rely on fatty acid ß-oxidation for energy. The accumulation of intracellular lipids and fatty acids in the myocardium usually results in lipotoxicity, which impairs myocardial function. Adipsin may play an important protective role in the pathogenesis of DCM. The aim of this study is to investigate the regulatory effect of Adipsin on DCM lipotoxicity and its molecular mechanism. METHODS: A high-fat diet (HFD)-induced type 2 diabetes mellitus model was constructed in mice with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg). Liquid chromatography-tandem mass spectrometry (LC-MS/MS), glutathione-S-transferase (GST) pull-down technique, Co-immunoprecipitation (Co-IP) and immunofluorescence colocalization analyses were used to investigate the molecules which can directly interact with Adipsin. The immunocolloidal gold method was also used to detect the interaction between Adipsin and its downstream modulator. RESULTS: The expression of Adipsin was significantly downregulated in the HFD-induced DCM model (P < 0.05). Adipose tissue-specific overexpression of Adipsin significantly improved cardiac function and alleviated cardiac remodeling in DCM (P < 0.05). Adipsin overexpression also alleviated mitochondrial oxidative phosphorylation function in diabetic stress (P < 0.05). LC-MS/MS analysis, GST pull-down technique and Co-IP studies revealed that interleukin-1 receptor-associated kinase-like 2 (Irak2) was a downstream regulator of Adipsin. Immunofluorescence analysis also revealed that Adipsin was co-localized with Irak2 in cardiomyocytes. Immunocolloidal gold electron microscopy and Western blotting analysis indicated that Adipsin inhibited the mitochondrial translocation of Irak2 in DCM, thus dampening the interaction between Irak2 and prohibitin (Phb)-optic atrophy protein 1 (Opa1) on mitochondria and improving the structural integrity and function of mitochondria (P < 0.05). Interestingly, in the presence of Irak2 knockdown, Adipsin overexpression did not further alleviate myocardial mitochondrial destruction and cardiac dysfunction, suggesting a downstream role of Irak2 in Adipsin-induced responses (P < 0.05). Consistent with these findings, overexpression of Adipsin after Irak2 knockdown did not further reduce the accumulation of lipids and their metabolites in the cardiac myocardium, nor did it enhance the oxidation capacity of cardiomyocytes expose to palmitate (PA) (P < 0.05). These results indicated that Irak2 may be a downstream regulator of Adipsin. CONCLUSIONS: Adipsin improves fatty acid ß-oxidation and alleviates mitochondrial injury in DCM. The mechanism is related to Irak2 interaction and inhibition of Irak2 mitochondrial translocation.

Secondary metabolites isolated from Agrimonia pilosa Ledeb.

A pilot study on the ethanol extracts of Agrimonia pilosa found to have anti-α-glucosidase and anti-inflammatory activities. Subsequent chemical study afforded a new phenylethyl isocoumarin glycoside (1) and eight known compounds (2-9). The structure of 1 was elucidated by comprehensive spectroscopic analysis and chemical transformations. All compounds showed modest α-glucosidase inhibitory activity (IC50 values ranging from 36.8 to 210.7 µM), which was lower than that of the positive control acarbose (IC50=301.9 µM). Those compounds except inactive compounds 3 and 6 showed weak anti-inflammatory activity.[Formula: see text].

Two new monoterpene esters from Illigera paviflora Dunn roots.

Two new monoterpene esters, illigerates H and I (1 and 2), and six known compounds actinodaphine (3), bulbocupnine (4), stephanine (5), hypserpanine B (6), betulinic acid (7) and gallic acid (8) were obtained from the root of Illigera paviflora Dunn. Their structures were elucidated by spectroscopic analysis. Anti-inflammatory and α-glucosidase inhibitory activity of some isolated compounds were assessed. Two monoterpenes 1 and 2 exhibited weak in vitro anti-inflammatory activity (IC50 64.5 ± 5.3 and 79.2 ± 7.5 µM) while compounds 3-6 showed inhibition of α-glucosidase with IC50 values ranged from 87.17 to 118.74 µM.

N-containing compounds of macromycetes.

This review surveys the chemical, biological, and mycological literature dealing with the isolation, structural elucidation, biological activities, and synthesis of nitrogen-containing compounds from the fruiting bodies or the culture broths of macromycetes.

Anti-inflammatory monoterpene esters from the stems of Illigera aromatica.

Two new monoterpene esters illigerates F and G (1 and 2) together with 5 know compounds illigerate A (3), illigerate C (4), actinodaphnine (5), N-methylactinodaphnine(6) and N-methyllaurotetanine(7) were isolated from Illigera aromatica S. Z. Huang et S. L. Mo. Their structures were identified by extensive NMR data and by comparing with the known compounds. The anti-inflammatory activity of four monoterpenes (1 - 4) was evaluated by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated murine macrophage RAW 264.7 cells and four monoterpenoids exhibited inhibitory effect with IC50 values of 71.5 ± 7.3, 74.7 ± 5.6, 48.0 ± 7.4 and 65.1 ± 3.7 µM, respectively.

Vibralactones D-F from cultures of the basidiomycete Boreostereum vibrans.

Three new metabolites, vibralactones D-F (1-3) were isolated from cultures of the basidiomycete Boreostereum vibrans. The relative configuration of 1 was established on the basis of X-ray diffraction analysis, while the absolute configurations of 1-3 were assigned using a modified Mosher's method. Compound 1 showed weak inhibitory activities against isozymes of 11beta-hydroxysteroid dehydrogenases (HSD) with IC(50) values of 85.7 microM (human HSD1), 295.2 microM (mouse HSD1), and 87.1 microM (human HSD2).

A new isoprenyl phenyl ether riboside from the culture of basidiomycete Laccaria amethystea.

A new isoprenyl phenyl ether riboside, 3-(3-methylbut-2-enyloxy)-4-O-alpha-D-ribofuranose benzoic acid methyl ester (1), was isolated from the culture of basidiomycete Laccaria amethystea. The structure of 1 was elucidated on the basis of extensive spectroscopic analysis.

Laxative Metabolites from the Leaves of Moringa oleifera.

Three new flavonoids, quercetin-3-O-6-[methyl-(S)-3-hydroxy-3-methylglutaroyl(1→6]-ß-d-glucopyranoside (1), kaempferol-3-O-[methyl-(S)-3-hydroxy-3-methylglutaroyl(1→6)]-ß-d-glucopyranoside (2), and quercetin-3-O-6-[(E)-4-methoxy-5-methylhexa-2,4-dienoatyl(1→6)]-ß-d-glucopyranoside (3), and two new alkaloids, 5-dehydroxymethyl-pyrrolemarumine 4″-O-α-l-rhamnopyranoside (4) and N1-methyl-N2-((4-O-α-l-rhamnopyranoside)benzyl) oxalamide (5), together with 45 known compounds (6-50) were isolated from the leaves of Moringa oleifera Lam. Among those compounds, 1-octacosanol (50), a straight-chain 28-carbon alcohol, exhibited good activity against diphenoxylate-induced constipation in mice, which is obtained as a laxative constituent from the plant for the first time. In order to have an accurate understanding of the content of compound 50, a quantification with gas chromatography-tandem mass spectrometry (GC-MS/MS) was carried out. The anti-inflammatory and α-glucosidase inhibitory activity of some compounds also was assessed.

Speciosins A-K, oxygenated cyclohexanoids from the basidiomycete Hexagonia speciosa.

Eleven new oxygenated cyclohexanoids, speciosins A-K (1-11), and aporpinone A (12) were isolated from broth cultures of the basidiomycete Hexagonia speciosa. Their structures were elucidated on the basis of extensive spectroscopic analysis, while the structure of 8 was additionally confirmed by analysis of single-crystal X-ray diffraction data.

Two new cleistanthane diterpenes and a new isocoumarine from cultures of the basidiomycete Albatrellus confluens.

Two new cleistanthane-type diterpenes, 3alpha,5alpha,8beta-trihydroxycleistanth-13(17),15-dien-18-oic acid (1) and 8beta-hydroxy-18-norcleistanth-4(5),13(17),15-trien-3-one (2), a new isocoumarine, 3R-(2R-hydroxypropyl)-8-hydroxyl-7-methyl-3,4-dihydroisocoumarine (3), along with three known aurovertins, aurovertins B (4), C (5) and E (6), four known polyesters, orbuticin (7), BK223A (8), BK223B (9) and 15G256alpha-2-me (10), and a known isocoumarine, 3R-6-hydroxymellein (11), were isolated from cultures of the basidiomycete Albatrellus confluens. The structures of these compounds were established on the basis of spectroscopic and chemical methods.

Vibralactone Biogenesis-Associated Analogues from Submerged Cultures of the Fungus Boreostereum vibrans.

A scale-up fermentation of the fungus Boreostereum vibrans facilitated the isolation of six new vibralactone biogenesis-associated analogues, namely vibralactamide A (1), vibralactone T (2), 13-O-lactyl vibralactone (3), 10-O-acetyl vibralactone G (4), (11R,12R)- and (11S,12R)-vibradiol (5, 6). Their structures were established via extensive spectroscopic analyses, specific optical rotation comparison, and Snatzke's method. The biosynthetic pathway for vibralactamide A was postulated. The absolute configuration of vibralactone B was revised by single crystal X-ray diffraction analysis. This work puts the divergent vibralactone biosynthesis pathway one step further and expands the structural diversity of vibralactone-associated compounds.

Two new biphenyls from the stems of Garcinia tetralata.

Two new biphenyls (1 and 2) and three known xanthones (3-5) were isolated from the ethanol extract of the stems of Garcinia tetralata. Structural elucidations of 1-2 were elucidated by spectroscopic methods including extensive 1D- and 2D-nuclear magnetic resonance spectroscopy techniques. Compounds 1-2 showed anti-rotavirus activities with SI above 10.

Isoprenylated cyclohexanoids from the basidiomycete Hexagonia speciosa.

Nine oxygenated cyclohexanoids, speciosins L-T (1-9) as well as a 5H-furan-2-one metabolite, 5'-O-acetylaporpinone A (10), together with known analogs, speciosins A, B, D, E, F, I and K (11-17), and aporpinone A (18), were isolated from a scale-up cultures of the basidiomycete Hexagonia speciosa. Their structures were elucidated by analysis of spectroscopic data, including 1D and 2D NMR. Speciosin B (12) showed significant cytotoxicity against several tumor cell lines with IC50 values in the range 0.23-3.30 µM.

Highly functionalized daphnane diterpenoids from Trigonostemon thyrsoideum.

Trigonothyrins A-C (1-3), which are highly functionalized daphnane diterpenoids, were isolated from the stems of Trigonostemon thyrsoideum. Compounds 1-3 represent the first examples of daphnanes with an oxygen-bridged four-membered-ring system, and a linkage mode of 12,13,14-orthoester. Compound 3 was observed to inhibit HIV-1 induced cytopathic effects. The EC(50) value was 2.19 microg/mL, and the therapeutic index (TI) was more than 90.

Derivatives of vibralactone from cultures of the basidiomycete Boreostereum vibrans.

Four new natural products possessing vibralactone skeleton, 1,5-secovibralactone (1), vibralactone B (2), vibralactone C (3) and acetylated vibralactone (4), together with known compound vibralactone (5), had been isolated from cultures of the basidiomycete Boreostereum vibrans. The structures of 1-4 were elucidated on the basis of spectroscopic methods. The absolute configuration of 1 was suggested to be S by computational methods.