Isodon eriocalyx and its bioactive component Eriocalyxin B enhance cytotoxic and apoptotic effects of gemcitabine in pancreatic cancer.

BACKGROUND: Pancreatic cancer, associated with poor prognosis and low survival rate, has been the fourth leading cause of cancer-related death in the US. Although gemcitabine (Gem) is the first-line chemotherapeutic drug in the management of pancreatic cancer, the median survival extension is only 1.5 months, indicating unsatisfactory clinical results. Therefore, exploring agents that can enhance the anti-cancer activity of Gem would be an attractive strategy. PURPOSE: Our previous studies have demonstrated that eriocalyxin b (EriB), an ent­kaurane diterpenoid isolated from Isodon eriocalyx (Dunn.) Hara, possesses anti-pancreatic cancer effects, thus acting as a potential therapeutic agent. In this study, we further investigated whether EriB or the ethanol extract of I. eriocalyx (Isodon) could potentiate the cytotoxic activity of Gem in human pancreatic adenocarcinoma cells. In addition, the mechanism associated with their effects was also studied. METHODS: The anti-proliferation effect was assessed by MTT assay and Ki-67 immunostaining. The combination effect (addition, synergism and antagonism) of various agents was calculated by the Calcusyn software (Biosoft), utilizing the T.C. Chou Method. Apoptosis was detected using Annexin V and PI double staining followed by quantitative flow cytometry. Protein expression regulated by various treatments was analyzed by western blotting. RESULTS: The combination index revealed that Gem and EriB (or Isodon extract) had synergistic anti-proliferative effect. Both cellular apoptotic and anti-proliferative effects of Gem were significantly increased after combination with EriB (or Isodon extract). The underlying mechanisms involved in the combination effects were elucidated, which include: (1) increased activation of the caspase cascade; (2) reduction of PDK1 and AKT phosphorylation; (3) induction of JNK phosphorylation by Isodon and Gem combination. CONCLUSION: Gem and EriB (or Isodon extract) taken together in combination regulated PDK1/AKT1/caspase and JNK signaling and promoted apoptosis synergistically, which may contribute to the much increased anti-proliferative activity compared to either agent alone.

Two new rearranged abietane diterpenoids from tropical Isodon coetsa.

Two new rearranged abietane diterpenoids, sincoetsin A (1) and sincoetsin B (2), were isolated from the aerial part of Isodon coetsa (Buth-Ham ex D.Don) Hara collected in Singapore, and their structures were determined by spectroscopic methods, especially 2D NMR techniques.

Two new triterpenoids from Picria fel-terrae.

Two new triterpenoids, picfeltarraegenin VII (1) and picfeltarraenin X (2), have been isolated from Picria fel-terrae Lour., along with three known ones, picfeltarraegenin VI (3), picfeltarraenins VI (4) and VII (5). Their structures have been elucidated by means of spectroscopic methods.

Leiocyclocin C and D, two cyclopeptides from Goniothalamus leiocarpus.

Two new cyclopeptides, leiocyclocin C (1) and D (2), were isolated from the seeds of Goniothalamus leiocarpus (Annonaceae). Their structures were determined as cyclo-(Gly1-Ser-Pro2-Tyr2-Gly2-Tyr1-Pro1-Pro3) and cyclo-(Gly1-Leu-Pro1-Gly2-Phe-Tyr-Pro2), respectively, by means of spectral and chemical methods.

Constituents from Lethariella cladonioides.

The isolation from the acetone extract of Lethariella cladonioides of the new compound cladonioidesin (1) and 10 other constituents is reported.

Secoiridoid constituents from the fruits of Ligustrum lucidum.

Two secoiridoid glucosides, lucidumosides A and B, as well as six known glucosides, oleoside dimethyl ester, ligustroside, oleuropein, nuezhenide, isonuezhenide, and neonuezhenide, were isolated from the fruits of Ligustrum lucidum. Their structures were elucidated by spectroscopic methods.

Constituents from the roots of Semiaquilegia adoxoides.

The isolation of griffonilide (1), lithospermoside (2) and magnoflorine (3) from the roots of Semiaquilegia adoxoides is reported.

[Studies on chemical constituents of Stellera chamejasma L].

OBJECTIVE: Isolate and identify the bioactive compounds from the root of Stellera chamejasma. METHOD: The compounds were extracted with solvents, isolated by column chromatography and identified by spectroscopic methods. RESULT: Seven compounds were isolated and identified as umbelliferone(1); daphnoretin (2); 2,6-dimethoxyl p-benzoquinone(3); (-)-eudesmin(4); (+)-matairesinol(5); lirioresinol B(6) and daucosterol(7). CONCLUSION: Compounds 3, 4 and 5 were isolated from the plant for the first time.

Gallotannins and related polyphenols from Pistacia weinmannifolia.

Two new gallotannins, pistafolins A (1) and B (2), were isolated from the leaf extract of Pistacia weinmannifolia. Their structures were determined by spectral methods. Four known gallotannins (3-6), seven known flavonoid glycosides (7-13), along with 1-O-beta-D-(6'-O-galloyl)-glucopyranosyl-3-methoxy-5-hydroxybenzen e (14), gallic acid (15), methyl gallate (16), (+)-catechin (17), and (+)-gallocatechin (18), were also isolated. Some of these compounds were tested for their cytotoxicity toward K562 cells, and two small molecular phenolic compounds, 15 and 18, showed significant inhibitory effects with IC50 values less than 5 micrograms/ml.

Constituents of Craspedolobium schochii.

Nine phenolic compounds, including a new one, were isolated from 70% acetone extract of Craspedolobium schochii. The new compound was identified as 3-(3,4-dimethoxy-2-hydroxyphenyl)-7-hydroxy-coumarin (1) on the basis of spectroscopic evidence.

New steroids from Clerodendrum colebrookianum.

Five new steroids, colebrin A-E (1-5) were isolated from the aerial parts of Clerodendrum colebrookianum. The structures of the new compounds were elucidated on the basis of spectral evidence.

Constituents from Lonicera japonica.

Five caffeoylquinic acids and esters (1-5), including a new compound, 3,5-dicaffeoylquinic acid butyl ester (5), were isolated from the flowers and buds of Lonicera japonica and their structures were determined by NMR spectral analysis.

Rearranged taxanes from the bark of Taxus yunnanensis.

Five new 11(15-->1)-abeo-taxane diterpenoids, taxuyunnanines K-O (1-5), were isolated from an ethanol extract of the bark of Taxus yunnanensis, and their structures were determined using MS and NMR techniques. Compounds 1/2 and 4/5 are rearranged taxane diterpenoids possessing an opened oxetane ring moiety at C4(20). Compounds 4/5 are rearranged taxoids lacking an oxygenated functionality at C-4.

Diterpenoids from Isodon lophanthoides.

A new diterpenoid was isolated from the leaves of Isodon lophanthoides, together with two known diterpenoids, lophanic acid and 8(17),12,14-labdatriene-19-oic acid. The structure of the new compound was determined to be 11 beta-hydroxyisopimara-8,15-diene-3-one (1) on the basis of spectroscopic evidence.

A new ent-kaurane diterpenoid from Isodon phyllostachys.

A new ent-kaurane diterpenoid, phyllostachysin C (1), together with five known compounds, sculponeatins B and C, nodosin, ursolic acid and 2 alpha-hydroxyursolic acid, were isolated from the leaves of Isodon phyllostachys. The structure of 1 was elucidated on the basis of its spectral properties.

New 7,20:14,20-diepoxy ent-kauranoids from Isodon xerophilus.

Three new 7,20:14,20-diepoxy-ent-kaurane diterpenoids, xerophilusins A-C (1-3), together with a known one, macrocalin B (4), were isolated from the leaves of Isodon xerophilus. Their structures were elucidated on the basis of their spectral properties and X-ray crystallographic analysis. Compounds 1, 2, and 4 showed significant cytotoxic activity against K562, HL-60, and MKN-28 cells.

Colebroside A, a new diglucoside of fatty acid ester of glycerin from Clerodendrum colebrookianum.

Colebroside A (1), a new diglucoside of fatty acid ester of glycerin, was isolated from the aerial parts of Clerodendrum colebrookianum Walp., along with nine known compounds (2-10). Their structures were elucidated by spectroscopic and chemical methods. Compounds 2, 3, 4, 5, 7, 8, 9 and 10 have been obtained from this plant for the first time.

Hydrolyzable tannins and related polyphenols from Eucalyptus globulus.

Eucaglobulin (1), a new complex of gallotannin and monoterpene, was isolated from the leaves of Eucaloptus globulus. Its structure was elucidated on the basis of spectral data. Four known hydrolyzable tannins [tellimagrandin I (2), eucalbanin C (3), 2-O-digalloyl-1,3,4-tri-O-galloyl-beta-D-glucose (4), 6-O-digalloyl-1,2,3-tri-O-galloyl-beta-D-glucose (5)], as well as gallic acid (6) and (+)-catechin (7), were also isolated. The antibacterial effects of some of these compounds were examined.

ent-kaurane diterpenoids from Isodon lungshengensis.

Six new ent-kaurane diterpenoids, lungshengenins B-G (1-6), together with three known diterpenoids, lungshengenin A (7), inflexin (8), and lushanrubescinsin C (9), were isolated from the leaves and tender branches of Isodon lungshengensis. Their structures were elucidated by means of spectroscopy, mainly 1D and 2D NMR techniques. Lungshengenins A (7), C (2), and G (6) were cytotoxic toward K562 cells, having IC(50) values equal to or less than 10 microg/mL.

Chemical constituents of Isodon melissoides.

Four new diterpenoids, melissoidesin E (1), F (2), G (4) and H (5), together with one known diterpenoid and two lignan glycosides, were isolated from aerial parts of Isodon melissoides. Their structures were established by spectral analysis and comparison with related compounds. The lignan glycosides (compounds 7 and 8) were the first examples to be isolated from the genus Isodon plants.