Sunpollenol and five other rearranged 3,4-seco-tirucallane-type triterpenoids from sunflower pollen and their inhibitory effects on Epstein-Barr virus activation

Six new rearranged 3,4-seco-tirucallane-type triterpenoids (1-6) have been isolated from the diethyl ether extract of the pollen grains of sunflower (Helianthus annuus). These compounds were evaluated with respect to their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells. All of the compounds tested showed potent inhibitory effects on EBV-EA activation (97-100% inhibition at 1 x 10(3) mol ratio/TPA).     

Cucurbitane glycosides from the fruits of Siraitia gros venorii and their inhibitory effects on Epstein-Barr virus activation

Six new cucurbitane glycosides, mogroside II B (2), 11-deoxymogroside III (4), 7-oxomogroside II E (5), 7-oxomogroside V (6), 11-oxomogroside II A1 (7), and 11-oxomogroside IV A (8), and two known but new naturally occurring cucurbitane glycosides, mogroside II A1 (1) and mogroside III A2 (3), were isolated from an ethanol extract of the fruits of Siraitia grosvenorii. Upon evaluation of compounds 1-8 for inhibitory effects against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), all compounds exhibited inhibitory effects with IC50 values of 346-400 mol ratio/32 pmol TPA. In addition, compounds 1-8 showed weak inhibitory effects on activation of (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor.     

Lucidenic acids P and Q, methyl lucidenate P, and other triterpenoids from the fungus Ganoderma lucidum and their inhibitory effects on Epstein-Barr virus activation

A new triterpene acid, lucidenic acid P (1a), and two new triterpene acid methyl esters, methyl lucidenates P (1b) and Q (2b), were isolated and characterized from the fruiting body of the fungus Ganoderma lucidum. Their structures were elucidated on the basis of spectroscopic methods. In addition, eight known triterpene acids, lucidenic acids A (3a), C (4a), D(2) (5a), E(2) (6a), and F (7a) and ganoderic acids E (9a), F (10a), and T-Q (11a), and six known triterpene acid methyl esters, methyl lucidenates A (3b), D(2) (5b), E(2) (6b), F (7b), and L (8b) and methyl ganoderate F (10b), were isolated and identified from the fungus. All of the triterpenoids, with the exception of 7a, were evaluated with respect to their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, which is known to be a primary screening test for antitumor promoters. All of the compounds tested showed potent inhibitory effects on EBV-EA induction (96-100% inhibition at 1 x 10(3) mol ratio/TPA).     

Studies on inhibitors of skin-tumor promotion. Inhibitory effects of triterpenes from Cochlospermum tinctorium on Epstein-Barr virus activation

Arjunolic acid, an oleanene-type triterpene isolated from the rhizome of Cochlospermum tinctorium, its triacetate derivative, and their methyl esters were tested using the short-term in vitro assay on EBV-EA activation in Raji cells induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Their inhibitory effects on skin tumor promotors were found to be greater than those of previously studied natural products.     

Absolute configuration of sesquiterpenes from Crossopetalum tonduzii and their inhibitory effects on Epstein-Barr virus early antigen activation in Raji cells

Two new sesquiterpenoids (1 and 2) with a dihydro-beta-agarofuran skeleton were isolated from Crossopetalum tonduzii. Their structures were elucidated on the basis of spectral analysis, including homonuclear and heteronuclear correlation NMR experiments (COSY, ROESY, HSQC, and HMBC). Their absolute configurations were determined by CD studies on 3, the benzoylated derivative of 1. Chemical correlations have allowed the absolute configurations of 4 and 5, two previously known dihydro-beta-agarofuran analogues, to be reported for the first time. Compounds 1, 2, and 5 showed strong antitumor-promoting effects on Epstein-Barr virus early antigen (EBV-EA) activation.     

Euphane and tirucallane triterpenes from the roots of Euphorbia kansui and their in vitro effects on the cell division of Xenopus

Four new euphane-type triterpenes, kansenone (1), kansenonol (3), 11-oxo-kansenonol (4), kansenol (5), and a new tirucallane-type triterpene, epi-kansenone (2), were isolated from a 60% EtOH extract of Euphorbia kansui, together with alpha-euphol. Their structures were elucidated on the basis of extensive analysis of their 1D and 2D NMR spectral data. This appears to be the first report of the natural occurrence of euphane/tirucallane-type triterpenes with a ketone at C-7. In vitro treatment of cultured individual Xenopus laevis cells at the blastular stage with 1-4 significantly arrested cleavage of the cells (10 microg/mL of each compound resulted in >50% cleavage arrest).     

Interiotherins C and D,two new lignans from Kadsura interior and antitumor-promoting effects of related neolignans on Epstein-Barr virus activation

Two new lignans, interiotherins C (1) and D (2), together with the known compounds interiorin (3), heteroclitin F (4), neokadsuranin (5), heteroclitin D (6), kadsurin (7), gomisin A (8), schisandrin C (9), interiotherin A (10), angeloylgomisin R (11), gomisin G (12), interiotherin B (13), and gomisin C (14), were isolated from the stems of Kadsura interior. The structures and stereochemistries of the new compounds were determined from mass, CD, and NMR spectral data. Fourteen neolignans were screened as potential antitumor promoters by examining their ability to inhibit Epstein-Barr virus early antigen (EBV-EA) activation (induced by 12-O-tetradecanoylphorbol-13-acetate) in Raji cells. Neokadsuranin (5) and schisandrin C (9) were the most potent compounds. These data suggest that some neolignans might be valuable antitumor promoters or chemopreventors.     

Inhibitory effects of antrodins A–E from Antrodia cinnamomea and their metabolites on hepatitis C virus protease

Antrodia cinnamomea is a highly valued folk medicine used for liver cancer, a disease often caused by the long term infection of hepatitis C virus (HCV). In the present study, the maleic and succinic acid constituents (antrodins A–E) of this medicinal fungus, the in vivo metabolites of antrodin C and the analogue of one of the metabolites were tested for their inhibitory activity on HCV protease. Most of the compounds showed potent inhibitory activity, with antrodin A being the most potent (IC₅₀ = 0.9 µg/mL). Antrodin A was isolated as one of the constituents of A. cinnamomea and was also detected as an in vivo metabolite of the major constituent antrodin C. The mode of inhibition for antrodin A on HCV protease was revealed by a Lineweaver‐Burk plot as competitive inhibition. These results strongly support the use of this folk medicine for liver cancer and HCV infection which is a global problem. Copyright © 2008 John Wiley & Sons, Ltd.     

Triterpenoids from the leaves of Diospyros kaki (persimmon) and their inhibitory effects on protein tyrosine phosphatase 1B

Phytochemical study on a methanol-soluble extract of the leaves of persimmon (Diospyros kaki) resulted in the isolation of two new ursane-type triterpenoids, 3alpha,19alpha-dihydroxyurs-12,20(30)-dien-24,28-dioic acid (1) and 3alpha,19alpha-dihydroxyurs-12-en-24,28-dioic acid (2), together with 12 known ursane- and oleanane-type triterpenoids (3-14). Triterpenoids with a 3beta-hydroxy group were found to inhibit protein tyrosine phosphatase 1B (PTP1B) activity, with IC50 values ranging from 3.1+/-0.2 to 18.8+/-1.3 microM, whereas those with a 3alpha-hydroxy moiety were not active.     

Antiproliferative effects of magnosalin derived from ‘Shin'i’ (Flos Magnoliae), a Japanese Sino-medicine,on cultured synovial cells of MRL/1 and C57BL/6J mice

The in vitro inhibitory effect of magnosalin, a compound derived from ‘Shin'i’ (Flos Magnoliae), on the proliferation of synovial cells from rheumatoid MRL/1 mice and normal C57BL/6J mice (control) was evaluated. DNA synthesis in synovial cells was induced with 5% fetal bovine serum (FBS) or interleukin-1α (IL-1α, 1 U/mL), and measured with a [³H]-thymidine incorporation assay. Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) were used in some experiments. FBS (5%)-stimulated proliferation (cell number) was significantly greater in MRL/1 mouse synovial cells than in C57BL/6J synovial cells. Magnosalin (23.9 μM ) inhibited [³H]-thymidine incorporation into both MRL/1 and C57BL/6J mouse synovial cells, whereas magnoshinin (23.4 μM ) inhibited [³H]-thymidine incorporation only into normal C57BL/6J synovial cells. Corticosterone, bucillamine, and tetrandrine, positive controls, also inhibited [³H]-thymidine incorporation into synovial cells. Reticuline (100 μM ) and coclaurine (100 μM ), structural moieties of tetrandrine, had no significant effects except for an inhibitory effect of coclaurine on normal C57BL/6J cells. Butylidenephthalide (100 μM ), a compound derived from Cnidium Rhizome, did not inhibit [³H]-thymidine incorporation into synovial cells of MRL/1 or normal mice. IL-1α, bFGF, and PDGF each stimulated [³H]-thymidine incorporation into synovial cells of normal mice in a concentration-dependent manner in the presence of 1% FBS. Of these cytokines, IL-1α was the most effective at the lowest concentration (0.57 pM ; 1 U/mL); it was as effective as 5% FBS. Both magnosalin (2.39 μM ) and tetrandrine (0.1 μM ) inhibited IL-1α (1 U/mL)-induced [³H]-thymidine incorporation into normal C57BL/6J synovial cells. Magnosalin appears to be an important lead compound for the development of a new class of antirheumatic agents.     

Effects of standardized extracts GK501, from Ginkgo biloba L., G115 from Panax ginseng C. A. Meyer,and their combination,gincosan® (PHL-00701), on the brain levels of biogenic monoamines and on the serum content of prolactin,growth hormone and ACTH

In experiments on old (26 months old) rats, we found that the extracts of Panax ginseng (G115), Ginkgo biloba (GK501) and their combination Gincosan® (PHL-00701) administered orally at two doses for 7 days induced changes in the levels of biogenic monoamines in some brain regions (frontal cerebral cortex, hippocampus, striatum, hypothalamus and pons). The most characteristic change was the increase produced by the two extracts and their combination in the serotonin level in all brain structures except for pons compared with controls. In the hippocampus G115, GK501 and their combination decreased the noradrenaline level. The same doses of G115, GK501 and their combination applied for 7 days to young (3 months old) and old (26 months old) rats caused significant changes in the blood level of prolactin (PRL), growth hormone (GH) and ACTH compared with age-matched controls: both G115 and GK501 decreased the serum level of PRL compared with age-matched controls; the hormone level being high in old controls, in extract-treated rats it became equal to that in young controls; G115 and PHL-00701 greatly increased the serum level of ACTH in both age groups compared with age-matched controls. Under conditions of induced immobilization and cold stress in young rats, the 7-day pretreatment with G115, GK501 and their combination led to significant changes in the blood levels of PRL, GH and ACTH compared with control untreated stressed and unstressed rats.