金疮小草中新的neo-克罗烷的分离

目的：进一步研究金疮小草（又称白毛夏枯草）中的neo-克罗烷二萜.方法：采用硅胶柱层析对二萜化合物进行分离,利用NMR对结构进行鉴定.结果：从氯仿提取部位分离已知化合物金疮小草素A,C,D（Ajugacumbins A,C,D,1,2,3）,ajugamarin A1（4）和新的neo-克罗烷二萜：金疮小草素H（ajugacumbin H,5）.     

Bioactive neo-clerodane diterpenoids from the whole plants of Ajuga ciliata Bunge

Ten new neo-clerodane diterpenes, ajugaciliatins A-J (1-5, 8-12), along with 17 known analogues (6, 7, 13-27) were isolated from the whole plants of Ajuga ciliata Bunge. Their structures were elucidated by spectroscopic data analysis (IR, ESIMS, HRESIMS, 1D and 2D NMR), and the configuration of 1 was confirmed by X-ray crystallography. All of the compounds were assessed for neuroprotective effects against MPP(+)-induced neuronal cell death in dopaminergic neuroblastoma SH-SY5Y cells. Compounds 2, 6, 7, 9, 10, 15-17, 19, and 20 exhibited moderate neuroprotective effects.     

Anti-inflammatory effect of Ajuga bracteosa Wall Ex Benth. mediated through cyclooxygenase (COX) inhibition

Ethnopharmacological relevance

Ajuga bracteosa Wall Ex Benth. (Labiateae) is described in Ayurveda for the treatment of rheumatism, gout, palsy and amenorrhea.

Aim of the study

The aim of present investigation is to study anti-inflammatory activity of Ajuga bracteosa, to understand possible mechanism of action and to identify the constituents responsible for its activity.

Materials and methods

The anti-inflammatory activity of 70% ethanolic extract was evaluated in TPA-induced mouse ear edema assay and in vitro cyclooxygenase (COX)-1 and COX-2 inhibitory activity was determined using EIA kits employing appropriate reference standards. Aajugarin I, lupulin A, withaferin A, reptoside and 6-deoxyharpagide were isolated from the 70% ethanolic extract by silica gel column chromatography.

Results

The 70% ethanol extract of whole plants of Ajuga bracteosa showed a significant (p < 0.05) and dose-dependent anti-inflammatory activity in an acute inflammation model at the dose of 0.5 and 1.0 mg/ear. The extract also exhibited a strong in vitro COX-1 and COX-2 inhibitory activity at 25 and 50 μg/mL concentration. Among the isolated compounds 6-deoxyharpagide exhibited highest COX-2 inhibition while rest of the compounds exhibited weak to moderate COX-1 and COX-2 inhibition at 30 μM concentration.

Conclusions

The results suggest that the 70% ethanol extract of Ajuga bracteosa possesses promising anti-inflammatory activity, which is possibly mediated through inhibition of COX-1 and COX-2 enzymes. The isolated constituents could be responsible in part for its anti-inflammatory and COX inhibitory activity. The study supports traditional use of Ajuga bracteosa for inflammatory diseases.     

Anti-inflammatory properties of Ajuga bracteosa in vivo and in vitro study and their effects on mouse model of liver fibrosis

Ethnopharmacological relevance

The entire plant of Ajuga bracteosa Wall has been used to treat various inflammatory disorders, including hepatitis, in Taiwan.

Aim

This study evaluated the hepatoprotective ability of Ajuga bracteosa extract (ABE).

Materials and methods

We investigated the inhibitory action of a chloroform fraction of ABE (ABCE) on lipopolysaccharide (LPS)-stimulated RAW264.7 cells and Kupffer cells. Hepatic fibrosis was induced in mice through the administration of CCl₄ twice a week for 8 weeks. Mice in three CCl₄ groups were treated daily with water and ABE throughout the duration of the experiment.

Results

In LPS-stimulated RAW264.7 cells and Kupffer cells, ABCE inhibited the production of NO and/or TNF-α and also blocked the LPS-induced expression of NO synthase. ABCE inhibited the activation of NF-κB induced by LPS, associated with the abrogation of IκBα degradation, with a subsequent decrease in nuclear p65 and p50 protein levels. The phosphorylation of MAPKs in LPS-stimulated RAW264.7 cells was also suppressed using ABCE. In the in vivo study, ABE protected the liver from injury by reducing the activity of plasma aminotransferase, and by improving the histological architecture of the liver. RT-PCR analysis showed that ABE inhibited the hepatic mRNA expression of LPS binding protein, CD14, TNF-α, collagen(α1)(I), and α-smooth actin.

Conclusion

These results indicate that ABE alleviated CCl₄-induced liver fibrosis, and that this protection is probably due to the suppression of macrophage activation.     

New stigmastane sterols from Ajuga salicifolia

A new sterol, ajugasalicigenin (1), and three new sterol glycosides, ajugasaliciosides F-H (2-4), were isolated and characterized from the aerial parts of Ajuga salicifolia. Compounds 1-4 are further representatives of the stigmastane type of sterols. Their cytotoxicity against KB (HeLa) and Jurkat T cancer cells was evaluated.     

ent-Labdane diterpenoids from Andrographis paniculata

Six new ent-labdane diterpenoids, 3-O-beta-D-glucopyranosyl-14,19-dideoxyandrographolide (1), 14-deoxy-17-hydroxyandrographolide (2), 19-O-[beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranoyl]-3,14-dideoxyandrographolide (3), 3-O-beta-d-glucopyranosylandrographolide (4), 12S-hydroxyandrographolide (5), and andrographatoside (6), together with 17 known analogues, were isolated from the aerial parts of Andrographis paniculata. The structures of 1-6 were determined by spectroscopic data analysis. All compounds isolated were evaluated for their inhibitory activity against several bacterial and fungal strains.     

Bis-spirolabdane diterpenoids from Leonotis nepetaefolia

Ten new bis-spirolabdane diterpenoids, leonepetaefolins A-E (1, 3, 5, 7, 9) and 15-epi-leonepetaefolins A-E (2, 4, 6, 8, 10), together with eight known labdane diterpenoids (11-18) as well as two known flavonoids, apigenin and cirsiliol, were isolated from the leaves of Leonotis nepetaefolia. The structures of the new compounds were determined on the basis of 1D- and 2D-NMR experiments including (1)H, (13)C, DEPT, (1)H-(1)H COSY, HSQC, HMBC, and NOESY. The absolute configuration of an epimeric mixture of 1 and 2 was determined by X-ray crystallographic analysis. The compounds isolated were evaluated for their binding propensity in several CNS G-protein-coupled receptor assays in vitro.     

ent-kaurane diterpenoids from Annona glabra

Three new kaurane diterpenoids, annoglabasin C (16alpha-acetoxy-ent-kauran-19-oic acid-17-methyl ester) (1), annoglabasin D (16alpha-acetoxy-ent-kauran-19-al-17-methyl ester) (2), and annoglabasin E (16alpha-hydro-19-ol-ent-kauran-17-oic acid) (3), and a new norkaurane diterpenoid, annoglabasin F (16alpha-acetoxy-19-nor-ent-kauran-4alpha-ol-17-methyl ester) (4), along with 13 known kaurane derivatives were isolated from the stems of Annona glabra. 16alpha-Methoxy-ent-kauran-19-oic acid (5) and 16alpha-hydro-ent-kauran-17,19-dimethyl ester (6) were obtained for the first time as natural products. The structures of compounds 1-6 were characterized by spectral analysis.     

Neoclerodane diterpenoids from Croton eluteria

Five new neoclerodane diterpenoids, rel-(3R,4S,5R,7R,8S,9R,10S,12R,20S)-7-acetoxy-15,16,12,20-diepoxy-3,4-dihydroxy-20-methoxyneocleroda-13(16),14-diene (1), rel-(3R,4S,5R,7R,8S,9R,10S,12R,20S)-7-acetoxy-15,16,12,20-diepoxy-3,4,20-trihydroxyneocleroda-13(16),14-diene (2), rel-(3R,4S,5S,6R,7S,8S, 9R,10S,12R,20S)-6,7-diacetoxy-3,4,15,16,12,20-triepoxy-20-hydroxyneocleroda-13(16),14-diene (3), rel-(3R,4S,5R,7R,8S,9R,10S,12R,20S)-7-acetoxy-3,4,15,16,12,20-triepoxy-20-hydroxyneocleroda-13(16),14-diene (4), and rel-(3R,4S,5R,7R,8S,9R,10S,12R,20R)-7,20-diacetoxy-3,4,15,16,12,20-triepoxyneocleroda-13(16),14-diene (5), have been isolated from the bark of Croton eluteria. The structures of the compounds 1-5 (cascarillins E-I) were determined by spectroscopic data interpretation.     

Isopimarane diterpenoids from Lycopus europaeus

A reinvestigation of the diterpene metabolites of Lycopus europaeus allowed the isolation of five new compounds, namely, four isopimarane derivatives (1-4) and 5,9-dihydroxygeranyllinalool (5). The structures of these substances were established by chemical and spectroscopic means.     

Immunosuppressive diterpenoids from Tripterygium wilfordii

A clinically used extract of Tripterygium wilfordii afforded three new diterpenoids-3beta,19-dihydroxyabieta-8,11,13-triene (triptobenzene L) (1); 12,19-dihydroxy-3-oxoabieta-8,11,13-triene (triptobenzene M) (2); and 19-hydroxy-3,7-dioxo-abieta-8,11, 13-triene (triptobenzene N) (3)-along with 14 known diterpenoids. The structures of 1-3 were established on the basis of spectroscopic studies. Of the known compounds, the stereochemistry at C-4 of triptonediol (4) was reassigned. Tripterifordin (8) and 13-epi-manoyl oxide-18-oic acid (9) showed significant inhibitory effects on cytokine production.     

Daphnane-type diterpenoids from Trigonostemon howii

Nine new daphnane-type diterpenoids (1-9), named trigohownins A-I, and four known analogues were isolated from Trigonostemon howii. Their structures were elucidated on the basis of extensive NMR and MS analyses. Trigohownins A (1) and D (4) exhibited moderate cytotoxic activity against the HL-60 tumor cell line, with IC50 values of 17.0 and 9.3 μM, respectively.     

Clerodane diterpenoids from Salvia splendens

Four new clerodane diterpenoids, salvisplendins A-D (1-4), have been isolated from an acetone extract of the flowers of Salvia splendens, together with an artifact (5), arising from salvisplendin D (4) by addition of diazomethane, and the already known clerodane olearin (6). The structures of the new compounds (1-5) were established mainly by 1D and 2D NMR spectroscopic studies and, in the case of salvisplendin A (1), by chemical correlation with splenolide B (7). Complete 1H and 13C NMR assignments for olearin (6), not published hitherto, are also reported.     

Labdane diterpenoids from Leonurus sibiricus

Six new labdane diterpenoids, preleosibirone A (1), 13-epi-preleosibirone A (2), isopreleosibirone A (3), leosibirone A (4), leosibirone B (5), and 15-epi-leosibirone B (6), were isolated from the leaves of Leonurus sibiricus. The absolute configurations of 1, 2, 5, and 6 were established by X-ray crystallographic analyses, and leosibirone A (4) was shown to be an artifact of the isolation process.     

Cytotoxic diterpenoids from Sapium insigne

Chemical investigation into the twigs and leaves of Sapium insigne afforded seven new diterpenoids, sapinsignoids A-G (1-7), together with 10 known diterpenoids. The structures of 1-7 were assigned on the basis of detailed spectroscopic analysis and chemical degradation. Compounds 1-4 exhibited significant cytotoxicity against the A-549 tumor cell line (IC(50) 0.2-1.8 μM), while compounds 1-3 showed moderate cytotoxicity against the HL-60 cell line (IC(50) 2.7-6.5 μM).     

Grindelane diterpenoids from Stevia subpubescens

Four new 9R,13R-epoxylabdane diterpenes (1-4) and a known clerodane derivative, 3,4beta-epoxy-5beta,10beta-cis-17alpha, 20alpha-clerod-13(14)-en-15,16-olide, were isolated from the leaves of Stevia subpubescens. The structures, which correspond to the grindelane class of diterpenoids, were elucidated by NMR data, chemical correlation, and single-crystal X-ray diffraction analysis of monoacetate 5. The absolute configuration of 1-4 is based on the optical activity of ketone 3 as compared with data of closely related substances.     

New diterpenoids from Viburnum awabuki

Eight new vibsane-type diterpenoids, vibsanins P-W (1-8), were isolated from the methanol extracts of the leaves and twigs of Viburnum awabuki. The structures were elucidated by 1D and 2D NMR spectral analysis, and their cytotoxicity against selected cancer cells was measured in vitro.     

Phytoecdysteroids from Ajuga macrosperma var. breviflora roots

Three new phytoecdysteroids, ajugacetalsterones C (1) and D (3) and breviflorasterone (2), were isolated from the roots of Ajuga macrosperma var. breviflora along with five known compounds, namely, 20-hydroxyecdysone, cyasterone, makisterone A, 20-hydroxyecdysone 3-acetate, and 20-hydroxyecdysone 2-acetate. The structures of 1-3 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic studies. The new compounds possess acetal oxygen bridges between C-26 and C-20/C-22, or C-26/C-23, or a lactone bridge between C-26 and C-23.     

Neoclerodane diterpenoids from Teucrium maghrebinum

Eight neoclerodane diterpenoids were identified in the extract of the aerial parts of Teucrium maghrebinum. Three of these, 12-epi-teucjaponin A (1), 12-epi-montanin D (2), and 12-epi-montanin B (3), are new natural products, whereas five, teucjaponin A, montanin D, 19-deacetylteuscorodol, teusalvin C (4), and montanin B, are already known. These eight compounds form four pairs of epimers at carbon C-12.     

Minor diterpenoids from Scutellaria polyodon

Four minor neoclerodane diterpene constituents were isolated from the aerial parts of Scutellaria polyodon. These compounds were characterized as the new scupolins J (1) and K (2) and the previously known scutalpin O (3) and scutalsin.