1-O-galloyl-6-O-(4-hydroxy-3,5-dimethoxy)benzoyl-beta-D-glucose, a new hepatoprotective constituent from Combretum quadrangulare.

A new gallic acid derivative, 1-O-galloyl-6-O-(4-hydroxy-3,5-dimethoxy)benzoyl-beta-D-glucose (1) has been isolated from an H2O-fraction of MeOH extract of Combretum quadrangulare seeds. Compound 1 exhibited potent hepatoprotective activity against D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes with an IC50 of 3.3 microM.

Three new triterpenes from the seeds of Combretum quadrangulare and their hepatoprotective activity.

Three new triterpenes of the lupane type, 2alpha,6beta-dihydroxybetulinic acid (1) and 6beta-hydroxyhovenic acid (2), and an oleanane type, 6beta-hydroxyarjunic acid (3), together with several known compounds, have been isolated from the MeOH extract of the seeds of Combretum quadrangulare. The structures of these compounds were elucidated on the basis of spectroscopic analysis, and their hepatoprotective activities were tested for D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes.

Hepatoprotective constituents of the seeds of Combretum quadrangulare.

Hepatoprotective effect of MeOH, MeOH-H2O (1:1) and H2O extracts of Combretum quadrangulare seeds were examined on D-galactosamine (D-GalN)/tumor necrosis factor-alpha(TNF-alpha)-induced cell death in primary cultured mouse hepatocytes. The MeOH extract showed the strongest inhibitory effect on D-GalN/TNF-alpha-induced cell death (IC50, 56.4 microg/ml). Moreover, the MeOH extract also significantly lowered the serum glutamic pyruvic transaminase (sGPT) level on D-GalN/lipopolysaccharide (LPS)-induced liver injury in mice. Bioguided separation of the MeOH extract led to the isolation of 38 compounds of various classes including triterpene glucosides, lignans and catechin derivatives. Among the isolated triterpene glucosides, lupane-type (1-3; IC50, 63.1, 59.8 and 76.2 microM, respectively) and ursane-type (11, mixture of 12 and 14; IC50, 30.2 and 34.6 microM, respectively) compounds exhibited strong hepatoprotective activity. 1-O-Galloyl-6-O-(4-hydroxy-3,5-dimethoxy)benzoyl-beta-D-glucose (26; IC50, 7.2 microM), methyl gallate (28; IC50, 19.9 microM), and (-)-epicatechin (31; IC50, 71.2 microM) also had a potent hepatoprotective effect on D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes.

Constituents of the Vietnamese medicinal plant Orthosiphon stamineus.

From the MeOH extract of the aerial part of Vietnamese Orthosiphon stamineus, five new isopimarane-type diterpenes [orthosiphols F-J (1-5)] and two new diterpenes [staminols A (6) and B (7)] with a novel carbon-framework, to which we proposed the name "staminane", and three new highly-oxygenated staminane-type diterpenes [staminolactones A (8) and B (9) and norstaminol A (10)1 were isolated. Moreover, staminolactone A (8) is 8,14-secostaminane-type and staminolactone B (9) is 13,14-secostaminane-type, while norstaminol A (10) is 14-norstaminen-type. Together with these new diterpenes, sixteen known compounds were also isolated and identified to be: 7,3',4'-tri-O-methylluteolin (11), eupatorin (12), sinensetin (13), 5-hydroxy-6,7,3',4'-tetramethoxyflavone (14), salvigenin (15), ladanein (16), tetramethylscutellarein (17), 6-hydroxy-5,7,4'-trimethoxyflavone (18), vomifoliol (19), aurantiamide acetate (20), rosmarinic acid (21), caffeic acid (22), oleanolic acid (23), ursolic acid (24), betulinic acid (25), and beta-sitosterol (26). All the isolated compounds were tested for their cytotoxicity towards highly liver metastatic murine colon 26-L5 carcinoma cells, and the new diterpenes, except for 4, and flavonoids (11, 12, 16, 18) showed cytotoxicity with an ED50 value between 10 and 90 microg/ml.

Quadranosides VI-XI, six new triterpene glucosides from the seeds of Combretum quadrangulare.

Six new triterpene glucosides, quadranosides VI-XI (1-6), belonging to three different [ursane- (1-4), oleanane- (5) and lupane-type (6)] triterpene classes, have been isolated from a MeOH extract of the seeds of Combretum quadrangulare KURZ (Combretaceae), together with nine known compounds, rosamutin (7), 28-O-beta-D-glucopyranosyl-6beta,23-dihydroxytormentic acid (8), arjunetin (9), arjunglucoside II (10), combreglucoside (11), chebuloside II (12), vitexin (13), (+)-catechin (14) and (-)-epigallocatechin (15). The structures of these compounds were elucidated by spectroscopic analysis.

Quadranosides I-V, new triterpene glucosides from the seeds of Combretum quadrangulare.

Five new triterpene glucosides, quadranosides I-V (1-5), have been isolated from a MeOH extract of the seeds of Combretum quadrangulare, together with 13 known compounds. The structures of compounds 1-5 were elucidated on the basis of spectroscopic analysis. Among the new triterpene glucosides, three compounds (1, 2, 5) showed significant hepatoprotective effects against D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes.

Hepatoprotective effect of Combretum quadrangulare and its constituents.

The MeOH extract of leaves of Combretum quadrangulare showed significant hepatoprotective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced experimental liver injury in mice and on D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes. Phytochemical investigation led to the isolation of thirty cycloartane-type triterpenes together with betulinic acid, beta-sitosterol, beta-sitosterol glucoside, 4 flavones (34-37), and 3 flavone C-glucosides (38-40). These compounds showed various potencies of hepatoprotective effect on D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes. Quadrangularol B (29), methyl quadrangularate I (33), kamatakenin (34), 5,7,4'-trihydroxy-3,3'-dimethoxyflavone (35), 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (36) and isokaempferide (37) showed strong inhibitory effect on TNF-alpha-induced cell death with IC50 values of 34.3, 33.7, 13.3, 22.4, 13.4 and 22.8 microM, respectively, whereas clinically-used silibinin had an IC50 value of 39.6 microM and glycyrrhizin showed very weak inhibitory effect. Methyl quadrangularates A (30) and N (32), norquadrangularic acid B (31) and vitexin (40) also showed potent inhibition on TNF-alpha-induced cell death with IC50 values of 45.7, 89.3, 67.6 and 40.1 microM, respectively. The flavonoids and some of the cycloartane-type triterpenes appeared to be the hepatoprotective principles of the leaves of C. quadrangulare.

Methyl quadrangularates A-D and related triterpenes from Combretum quadrangulare.

From the MeOH extract of leaves of Combretum quadrangulare, fifteen new cycloartane-type triterpenes, methyl quadrangularates A-D (1-4) and N-P (8, 6, 12), methyl 24-epiquadrangularate C (5), quadrangularic acid E (9), 23-deoxojessic acid (10), 1-O-acetyl-23-deoxojessic acid (11), quadragularols A (7) and B (13) and norquadrangularic acids B (14) and C (15) were isolated together with two known cycloartane-type triterpenes, methyl 23-deoxojessate (16) and 4beta,14alpha-dimethyl-5alpha-ergosta-9beta++ +,19-cyclo-24(31)-en-3beta-hydroxy-4alpha-carboxylic acid (17). Betulinic acid (18), beta-sitosterol (19), kamatakenin (20), isokaempferide (21), 5,7,4'-trihydroxy-3,3'-dimethoxyflavone (22) and 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (23) were also obtained from the same extract. The structures of the new compounds were elucidated on the basis of spectral analysis and chemical conversions. All the isolated compounds were tested for their cytotoxicity towards highly liver metastatic murine colon 26-L5 carcinoma cells, and the cycloartane-type triterpenes showed various degrees of cytotoxicity, whereas all the flavonoids possessed strong cytotoxicity with ED50 values equal to or less than 6 microM.

Thirteen novel cycloartane-type triterpenes from Combretum quadrangulare.

Thirteen novel cycloartane-type triterpenes were isolated from Combretum quadrangulare, a Vietnamese medicinal plant. The structures of the novel triterpenes were determined by spectroscopic methods as well as by chemical transformations. Among those compounds, quadrangularic acids F (1), G (2), and H (4) and 24-epiquadrangularic acid G (3) are the first examples of cycloartane-type triterpenes bearing carboxylic acid groups at both C-4 and C-20. Furthermore, norquadrangularic acid A (13) is the first example of a trinorcycloartane-type triterpene isolated from the genus Combretum.

Staminolactones A and B and norstaminol A: three highly oxygenated staminane-type diterpenes from Orthosiphon stamineus.

[formula: see text] Staminolactones A (1) and B (2) and norstaminol A (3), three highly oxygenated staminane-type diterpenes having mild cytotoxic activities against highly liver-metastatic colon 26-L5 carcinoma cells, were isolated from the aerial part of the Vietnamese medicinal plant Orthosiphon stamineus (Lamiaceae). Their structures were elucidated on the basis of the extensive spectral analyses.

Cytotoxic cycloartane-type triterpenes from Combretum quadrangulare.

Seven novel cycloartane-type triterpenes were isolated from Combretum quadrangulare, and their structures were elucidated on the basis of spectral analysis. All these compounds were tested for their cytotoxicity against murine colon 26-L5 carcinoma cells. Methyl quadrangularate B (2) and methyl quadrangularate D (4) exhibited potent cytotoxicity having ED50 values 9.54 and 5.42 microM, respectively.