Dibenzocyclooctadiene lignans from Kadsura coccinea

In vitro anti-allergic screening of medicinal herbal extracts revealed that the EtOAc extract of the rhizoma of Kadsura coccinea inhibited nitric oxide (NO) production in a lipopolysaccharide and recombinant mouse interferon-γ activated murine macrophage-like cell line, RAW264.7. Further fractionation of the EtOAc extract led to the isolation of two new dibenzocyclooctadiene lignans kadsuralignan G (1) and kadsuralignan L (2), and three known analog compounds. The absolute stereostructures were established by circular dichroism spectra. Both 1 and 2 showed moderate NO production inhibitory activities.     

Anti-inflammatory,free radical scavenging and alpha-glucosidase inhibitory activities of Hamelia patens and its chemical constituents

Context Hamelia patens Jacq. (Rubiaceae) is traditionally used to treat wounds, inflammation and diabetes. However, there is still a lack of scientific evidence to support these applications.

Objective The objective of this study is to evaluate the anti-inflammatory, antioxidant and antidiabetic activities of Hamelia patens, and identify its bioactive compounds.

Materials and methods Four extracts were obtained by maceration and liquid–liquid extraction: HEX, DCM–EtOAc, MeOH–EtOAc and MeOH–Aq. The anti-inflammatory effect was evaluated orally on rat paw carrageenan-induced oedema over 6?h (50, 200 and 500?mg/kg), and topically in mouse ear oedema induced by 12-tetradecanoylphorbol-13-acetate (TPA) after 4?h (0.5 and 1?mg/ear). We also evaluated myeloperoxidase levels in ear tissue, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging ability, and in vitro α-glucosidase inhibition. The chemical compounds were separated by column chromatography and identified by spectroscopic analysis.

Results We found that the oral administration of the HEX extract at 500 and 200?mg/kg significantly decreased the carrageenan-induced inflammation after 1 and 3?h, respectively. The MeOH–EtOAc extract significantly inhibited myeloperoxidase activity (83.5%), followed by the DCM–EtOAc extract (76%), β-sitosterol/stigmasterol (72.7%) and the HEX extract (55%), which significantly decreased oedema induced by TPA at both doses, giving a similar effect to indomethacin. We also found that the MeOH–EtOAc, MeOH–Aq and DCM–EtOAc extracts showed good DPPH scavenging activity (IC₅₀ values of 18.6, 93.9 and 158.2?μg/mL, respectively). The HEX extract showed the lowest α-glucosidase inhibition (an IC₅₀ value of 26.07?μg/mL), followed by the MeOH–EtOAc extract (an IC₅₀ value of 30.18?μg/mL), β-sitosterol/stigmasterol (IC₅₀ 34.6?μg/mL) and compound A ((6E,10E,14E,18E)-2,6,10,14,18,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene, an IC₅₀ value of 114.6?μg/mL), which were isolated for the first time from Hamelia patens.

Discussion and conclusion Hamelia patens possesses anti-inflammatory, antioxidant and α-glucosidase inhibitory activities, which support its traditional use. These effects can be attributed to the identified compounds.     

Three new isopimarane diterpenoids from Excoecaria acerifolia

Three new isopimarane diterpenoids named excoecarins F–H (1–3) were isolated from the EtOAc extract of the Chinese ethnodrug Gua-jing-ban (Excoecaria acerifolia Didr.). Their structures were elucidated by the analysis of spectroscopic data including 1D, 2D NMR and HR-MS. The anti-HIV-1 bioactivity test of 1 and 2 showed weak activity.     

A new chromone and a new aliphatic ester isolated from Daldinia eschscholtzii

Abstract

A new chromone and a new aliphatic ester were isolated from the EtOAc extract of myceliums of Daldinia eschscholtzii. Their structures were elucidated as (R)-5-hydroxy-8-methoxy-2-methylchroman-4-one (1) and (E)-6-(non-3-en-1-yl) -2H-pyran-2-one (2) by interpretation of the spectroscopic evidence.     

Lignans from the bark of Zanthoxylum simulans

Investigation on the EtOAc extract of the bark of Zanthoxylum simulans led to the isolation of four new lignans including zanthoxylumin A (1), zanthoxylumin B (2), ( ? )-magnolin (3), and ( ? )-pinoresinol-di-3,3-dimethylallyl ether (4). Their structures were established by comprehensive analysis of the spectral data, especially 1D and 2D NMR spectra.     

PAF antagonistic activity of 2-hydroxy-3-methoxybenzoic acid glucose ester fromGentiana scabra

In order to find out anti-platelet activating factor (PAF) from natural resources, Korean medicinal plants used for the treatments of peripheral circulation disorders were tested for their possible protective effects on PAF-induced anaphylactic shock. From the above screening, the methanol extract ofGentiana scabra showed a potent antagonistic activity against PAF. Water suspension of the extract was partitioned with CH₂Cl₂ and EtOAc, successively. The EtOAc fraction which showed the highest activity was chromatographed on silica gel to yield 6 fractions. From the fraction which showed higher PAF-antagonistic activity than the other fractions, compound1 was isolated by recrystallization. On the basis of spectral data, compound1 was identified as 2-hydroxy-3-methoxybenzoic acid glucose ester. The compound prevented the mice from the PAF-induced death at a dose of 300 μg/mouse.     

Two new threitol orsellinates from a sea mud-derived fungus,Ascotricha sp. ZJ-M-5

Two new d-threitol orsellinates (1–2) were isolated from the EtOAc extract of a sea mud-derived fungus, Ascotricha sp. ZJ-M-5, cultured in Czapek Dox broth. These two compounds featured in the symmetrical substitution of orsellinic acid or acetic acid, which was established on the basis of 1D and 2D NMR experiments. The characteristic optical rotations enabled the assignment of the absolute configuration.     

In vitro antimalarial activity of prenylated flavonoids from Erythrina fusca

Ethyl acetate (EtOAc) extract from the stem bark of Erythrina fusca showed a antimalarial activity against the multi-drug-resistant strain (K1) of Plasmodium falciparum, and six flavonoids, lupinifolin (1), citflavanone (2), erythrisenegalone (3), lonchocarpol A (4), liquiritigenin (5), and 8-prenyldaidzein (6), were isolated from the extract. Diprenylated flavanone 4 showed a notable antimalarial activity (IC₅₀; 1.6 μg/mL); however 1 and 3 did not show the activity, even though these compounds possessed prenylated substitution.     

A new erythrinan alkaloid from the seed of <Emphasis Type="Italic">Erythrina addisoniae</Emphasis>

Phytochemical study on the EtOAc extract of the seed of Erythrina addisoniae (Leguminosae) resulted in the isolation of a new erythrinan alkaloid, erysovine-N-oxide (1), along with eight known alkaloids, erysosalvinone (2), erysodine (3), 1H-indole-3-propanamide (4), glucoerysodine (5), erysotrine (6), erysovine (7), erythraline (8) and erysopine (9). Their chemical structures were identified on the basis of physicochemical and spectroscopic analyses.     

A new ascorbic acid derivative and two new terpenoids from the leaves and twigs of Rhododendron decorum

The phytochemical study of the ethanol extract of the leaves and twigs of Rhododendron decorum afforded a new ascorbic acid derivative (1), a new ionone analogue (2), a new ursane-type triterpenoid glucoside (3), and four known compounds (4?7). The structures were elucidated by spectroscopic analyses, including HRESIMS, 1D, and 2D NMR. The anti-neuroinflammatory activities of the compounds were evaluated by measuring inhibitory effects of LPS-induced NO production in BV2 cells.     

Anti-inflammatory lupane triterpenoids from Menyanthes trifoliata

A new lupane triterpenoid, 23-O-trans-feruloylcylicodiscic acid (1), as well as four known analogues (2?5), was isolated from the EtOAc fraction of Menyanthes trefoliata. The structure of compound 1 was elucidated on the basis of extensive spectroscopic analysis, including 2D NMR data. The structures of the known compounds were established by comparison of their spectroscopic data with that in the literature. Compounds 1, 2, and 4 exhibited certain anti-NO production activities.     

Two new compounds from an endophytic fungus Aspergillus sp. HS-05

Two new compounds, N-[4′-hydroxy-(E)-cinnamoyl]-l-tyrosine methyl ester (1) and methyl 4-methoxy-3-(3′-hydroxy-2′-methyl)propionyloxy-benzoate (2), were isolated from EtOAc extract of the fermentation broth of the endophytic fungus Aspergillus sp. HS-05. Their structures were elucidated by NMR, IR, UV, MS, and CD methods. Compounds 1 and 2 showed no anticancer activities against HL-60 cell lines (both of IC₅₀>100 μM) in vitro.     

Isolation of megastigmane sesquiterpenes from the silkworm (<Emphasis Type="Italic">Bombyx mori</Emphasis> L.) droppings and their promotion activity on HO-1 and SIRT1

The silkworm (Bombyx mori L.) droppings were extracted with 80% aqueous MeOH, and the concentrated extract was partitioned in succession with EtOAc, n-BuOH, and H₂O. From the EtOAc fraction, five megastigmane sesquiterpenes were isolated through repeated silica gel and ODS column chromatography. According to the results of spectroscopic data, such as NMR, MS, and IR, the chemical structures of the isolated compounds were determined as (3S,5R,8R)-3,5-dihydroxymegastigma-6,7-dien-9-one (1), (S)-dehydrovomifoliol (2), (6R,7E,9R) -9-hydroxy-4,7-megastigmadien-3-one (3), (3S,5R,6S,7E)-3,5,6-trihydroxy-7-megastigmen-9-one (4), (6R,9R)-9-hydroxy-4-megastigmen-3-one (5). Compounds 2 through 5 were isolated for the first time from silkworm droppings. GC/MS analysis indicated silkworm powder contained compound 3, and mulberry leaves contained compound 4. Compounds 1 and 5 increased the expression of heme oxygenase-1 and SIRT1 in HepG2 and HEK239 cells, respectively. Heme oxygenase-1 is considered to be an antioxidant enzyme that catabolizes heme to carbon monoxide, free iron and biliverdin, while SIRT1 is the mammalian homologue of the yeast silent information regulator (Sir)-2, which are involved in the suppression of inflammatory mediators or factors that may be used to improve atopy-related symptoms.     

Two new compounds from the broth of the marine fungus Penicillium griseofulvum Y19-07

Two new compounds, 4-hydroxyphenethyl methyl succinate (1) and 4-hydroxyphenethyl 2-(4-hydroxyphenyl)acetate (2), were isolated from the EtOAc extract of the broth of the marine fungus Penicillium griseofulvum Y19-07. Five known compounds were also obtained in this study. The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopy and mass spectrometry. All of the isolates were evaluated for their scavenging properties toward the 2,2-diphenyl-1-picrylhydrazyl free radical by spectroscopic assays. Also, in the cytotoxicity assay of the two new compounds against HL-60 and PC-3 prostate cancer cell lines, compound 2 showed potential activity with an IC₅₀ value of 64.5 μM against human HL-60 cancer cells.     

Sesquiterpenoids from Ferula fukanensis and their inhibitory effects on nitric oxide production

Six sesquiterpene derivatives, 2,3-dihydro-7-methoxy-2S*, 3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]furo[3,2-c]coumarin (1) and 2,3-dihydro-7-methoxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]furo[3,2-c]coumarin (2), nerolidol (3), 1-(2,4-dihydroxyphenyl)-3,7,11-trimethyl-3-ninyl-6(E),10-dodecadien-1-one (4), 1-(2,4-dihydroxyphenyl)-3,7-dimethyl-3-vinyl-8-(4-methyl-2-furyl)-6(E)-octen-1-one (5) and dshamirone (6) were isolated from an 80% aqueous methanol extract of the roots of Ferula fukanensis. The sesquiterpenoids inhibited nitric oxide (NO) production and inducible NO synthase gene expression by a murine macrophage-like cell line (RAW 264.7) [1], which was activated by lipopolysaccharide and recombinant mouse interferon-.     

Melanogenesis inhibitory compounds from Saussureae Radix

Ten compounds were isolated from the EtOAc soluble part of the MeOH extract of Saussureae Radix, with their effects on melanin production also evaluated in B-16 mouse melanoma cell lines stimulated with 3-isobutyl-1-methylxanthine (IBMX), an elevator of cellular cAMP. The compounds were identified as aplotaxene (1), 1β-hydroxy arbusculin A (2), costunolide (3), dehydrocostuslactone (4), 11β,13-dihydrocostunolide (5), reynosin (6), heptadec-(9Z)-enoic acid (7), β-sitosterol (8), linoleic acid methyl ester (9) and betulinic acid methyl ester (10). Compounds 2, 9 and 10 were identified from Saussureae Radix for the first time. Furthermore, compounds 2, 3 and 6 showed potent inhibitory effects on the IBMX-induced melanogenesis, in dose-dependent manners, with IC₅₀ values of 11, 3 and 2.5 μg/mL, respectively. As a positive control, arbutin exhibited an IC₅₀ value of 29 μg/mL.     

Anti-inflammatory constituents from the root of Litsea cubeba in LPS-induced RAW 264.7 macrophages

Context Litsea cubeba (Lour.) Pers. (Lauraceae) has long been used as a folk remedy in Traditional Chinese Medicine (TCM) for the treatment of rheumatic diseases. Previous studies from our laboratory indicated that L. cubeba extract showed anti-arthritic activity in rats.

Objective To study L. cubeba chemically and biologically and to find the potential constituents responsible for its anti-arthritic effect.

Materials and methods The compounds were isolated from the root of L. cubeba by column chromatography which eluted with PE:EtOAc gradient system, and the structures were elucidated by detailed spectroscopic data analysis; the anti-inflammatory activity of the isolated compounds was evaluated by lipopolysaccharide (LPS)-induced RAW 264.7 cells and the TNF-α and NO level were measured by ELISA (commercial kit); The iNOS and COX-2 mRNA expression were measured by RT-PCR and the phosphorylation of IκBα, IKKβ, P38 and Akt were determined by western blots.

Results A novel 9-fluorenone, 1-ethoxy-3,7-dihydroxy-4,6-dimethoxy-9-fluorenone (1), together with 4 known compounds, namely pinoresinol (2), syringaresinol (3), 9,9′-O-di-(E)-feruloyl-meso-5,5′-dimethoxysecoisolariciresinol (4) and lyoniresinol (5) were isolated from the root of L. cubeba for the first time. The IC₅₀ for NO inhibition on compounds 1 and 4 were 56.1?±?1.2 and 32.8?±?2.3?μM, respectively. The IC₅₀ for TNF-α inhibition were 28.2?±?0.9 and 15.0?±?1.0?μM, respectively. Both 1 and 4 suppress mRNA expression of iNOS, COX-2 and protein phosphorylation of IκBα, IKKβ in LPS-induced RAW 264.7 cells.

Discussion and conclusion Compounds 1 and 4 isolated from L. cubeba exhibited potent anti-inflammatory activity through the NF-κB signal pathway.     

Inhibition of key enzymes linked to type 2 diabetes by compounds isolated from Aframomum melegueta fruit

Context: The use of Aframomum melegueta K. Schum. (Zingiberaceae) fruit for treatment of diabetes has recently been established in Nigeria. However, compounds responsible for the antidiabetic action have not been identified.

Objective: The present study carried out the bioassay-guided isolation of possible bioactive compounds responsible for the antidiabetic action of A. melegueta fruit.

Materials and methods: The A. melegueta fruit was sequentially extracted using ethyl acetate (EtOAc), ethanol and water, and the most active extract (EtOAc) was subjected to column chromatography on a silica gel column using solvent gradient systems of hexane (HEX):EtOAc and EtOAc:MeOH and the isolation of compounds was guided by α-glycosidase and α-amylase inhibitory activities at various concentrations (30–240?μg/mL).

Results: According to the results, 3 arylalkanes, 6-paradol (1), 6-shogaol (2) and 6-gingerol (3) and a pentacyclic triterpene, oleanolic acid (4) were isolated from A. melegueta fruit. All the compounds exhibited inhibitory effects against α-amylase and α-glucosidase. 6-Gingerol (3) and oleanolic acid (4) showed higher inhibitory activity against α-amylase (IC₅₀: 6-gingerol: 81.78?±?7.79?μM; oleanolic acid: 91.72?±?1.63?μM) and α-glucosidase (IC₅₀: 6-gingerol: 21.55?±?0.45?μM; oleanolic acid: 17.35?±?0.88?μM) compared to the standard drug, acarbose and other isolated compounds. The kinetics of the enzyme action of the compounds showed a noncompetitive mode of inhibition.

Conclusion: The data of this study suggest that the 6-gingerol (3) and oleanolic acid (4) showed higher α-amylase and α-glucosidase inhibitory action and therefore could be responsible for the antidiabetic activity of A. melegueta fruit.     

The stem bark extracts of Cenostigma macrophyllum attenuates tactile allodynia in streptozotocin-induced diabetic rats

Abstract

Context. Cenostigma macrophyllum Tul. var. acuminata Teles Freire (Leguminosae- Caesalpinioideae) is popularly known as “caneleiro”. Previous studies showed antioxidant action and analgesic effects of the ethanol extract from the leaves of C. macrophyllum. The phytochemical evaluation of the stem bark revealed the presence of antinociceptive compounds.

Objective: To investigate the antinociceptive actions of the ethanol extract and ethyl acetate fraction from C. macrophyllum stem bark in streptozotocin (STZ)-induced diabetic rats and the involvement of opioid and nitrergic mechanisms.

Materials and methods: STZ-rats received the ethanol extract (E.EtOH 200 and 300?mg/kg, p.o.) during 5 weeks. In acute experiments, untreated diabetic rats were treated with the ethyl acetate fraction (F.EtOAc 250 and 500?mg/kg, p.o.), on the 28th day of diabetes induction when the opioid and nitrergic mechanisms were investigated. The mechanical nociceptive threshold (MNT) was determined by application of von Frey filaments.

Results: Data show that STZ-induced diabetic rats developed a significant tactile allodynia during 5 weeks. Diabetic rats that received E.EtOH (200 and 300?mg/kg) and F.EtOAc (250 and 500?mg/kg) had a pain threshold higher than those in the STZ-vehicle group. F.EtOAc effects were inhibited by pretreatment with naloxone and were not influenced by .-arginine.

Discussion and conclusion: The results suggest that the ethanol extract and ethyl acetate fraction of C. macrophyllum presented antinociceptive activity. Thus, F.EtOAc may be exerting its effect by affecting the opioid system, but nitrergic mechanisms are not detectable. The observed activity may be due to its gallic acid, lupeol and bergenin content.     

(+)-Cyclopenol,a new naturally occurring 7-membered 2,5-dioxopiperazine alkaloid from the fungus Penicillium sclerotiorum endogenous with the Chinese mangrove Bruguiera gymnorrhiza

One new naturally occurring 7-membered 2,5-dioxopiperazine alkaloid named (+)-cyclopenol (1), along with nine known compounds including viridicatol (2), 3-(dimethylaminomethyl)-1-(1,1-dimethyl-2-propenyl)indole (3), anacine (4), aurantiomide C (5), viridicatin (6), 3-O-methylviridicatin (7), verrucosidin (8), ergosterol (9), and ergosterol peroxide (10), was isolated from the EtOAc extract of fungus Penicillium sclerotiorum, an endophytic fungal strain isolated from Chinese mangrove Bruguiera gymnorrhiza. The chemical structure of the new compound 1 was elucidated on the basis of detailed spectroscopic analysis. The absolute configuration of 1 was determined by single-crystal X-ray analysis with Cu Kα radiation (λ = 1.54178 Å). To our knowledge, (+)-cyclopenol (1) represents the first example of 7-membered 2,5-dioxopiperazine isolated from mangrove endophytic fungus.