Dóra Rédei

Jatrophane diterpenes from Euphorbia esula as antiproliferative agents and potent chemosensitizers to overcome multidrug resistance.

Phytochemical study of whole, undried plants of Euphorbia esula led to the isolation of six new (1-6) jatrophane diterpene polyesters, named esulatins H-M, together with the known compounds 2α,3β,5α,7β,15β-pentaacetoxy-9α-nicotinoyloxyjatropha-6(17),11-dien-14-one (7), salicinolide (8), and euphosalicin (9). The structures and relative configuration of 1-6 were established on the basis of extensive spectroscopic analysis, including HRESIMS and one- and two-dimensional NMR techniques. All these compounds, together with diterpenes (10-14) isolated previously from this plant, were evaluated for their antiproliferative activity against HeLa, Ishikawa, and MCF7 cells. The multidrug-resistance-reversing activities were also investigated on L5178 mouse lymphoma cells transfected with the pHa MDR1/A retrovirus DNA. Preliminary structure-activity relationship data are discussed.

Unusual tigliane diterpenes from euphorbia grandicornis

Phytochemical study of the aerial parts of Euphorbia grandicornis led to the isolation of two new tigliane diterpenes, 16-angeloyloxy-13α-isobutanoyloxy-4β,9α,20-trihydroxytiglia-1,5-diene-3,7-dione (1) and 16-angeloyloxy-13α-isobutanoyloxy-4β,9α,7β-trihydroxytiglia-1,5-dien-3-one (2). The structures and relative configuration of the new compounds were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR experiments ((1)H NMR, JMOD, (1)H-(1)H COSY, NOESY, HSQC, and HMBC), mass spectrometry, and comparison with literature data. The biogenesis of 1 and 2 with respect to the unusual 5-en-7-one and 5-en-7-ol moieties is also discussed.

PHENYLPROPANOID GLYCOSIDES AND DITERPENOIDS FROM SALVIA OFFICINALIS

Sage (Salvia officinalis L., Lamiaceae) is a common medicinal and aromatic plant widely used in foods and in herbal medicinal products. Aerial parts of this plant were gathered in July 1999 in the Botanical Garden of the Institute of Ecology and Botany of the Hungarian Academy of Sciences, Vacratot, Hungary (VBI), where a voucher specimen (L 963/A) has been retained in the Herbarium.

Chemoprevention and inhibition of P-glycoprotein in cancer cells by Chinese medicinal herbs.

Many of the herbal extracts used in the Chinese clinical medical routine inhibit the growth of tumor cells. In the present work, extracts of 12 selected herbs were prepared with methanol, chloroform, ethyl acetate and water, and the effects of these on the multidrug resistance (MDR) and P‐glycoprotein of mouse lymphoma cells transfected with the human mdr1 gene and on a human lung alveolar epithelial cell line were investigated. The extracts were tested for antiproliferative effects, and the reversal of MDR in mouse lymphoma cells. The possible chemopreventive effect of the chloroform extracts was studied on the expression of cytomegalovirus (CMV) immediate‐early (IE) antigen in human lung cancer cells (A549). The antimicrobial effects of the extracts were tested on some representative micro‐organisms. Certain of the chloroform extracts of the plant materials were the most effective compounds on the reversal of MDR. Two of the chloroform extracts enhanced the antiproliferative effect of doxorubicin on MDR mouse lymphoma cells. The selected extracts did not show any antibacterial effect with the agar diffusion method. Certain chloroform extracts decreased the intermediate IE antigen expression of CMV in A459 cells. Copyright

Bioactivity-Guided Investigation of the Anti-Inflammatory Activity of Hippophae rhamnoides Fruits

According to modern ethnobotanical records, the fruit of Hippophae rhamnoides is effective in the treatment of different allergic symptoms. In order to obtain pharmacological evidence for this observation, the fruit was investigated for anti-inflammatory activity using in vivo animal models. Aqueous and 70% MeOH extracts were tested in 48/80-induced rat paw edema assay after oral administration, and it was found that the 70% MeOH extract (500 mg/kg) reduced significantly edema volume (0.660 ± 0.082 mL vs. control 0.935 ± 0.041 mL). Extracts of different parts of the fruit (pulp, peel, seed) were investigated in the same assay, and the peel extract was shown to exhibit maximum edema-reducing effect (0.470 ± 0.124 mL vs. control 0.920 ± 0.111 mL). This extract was used to elucidate the mode of action. Different inflammation inducers (serotonin, histamine, dextran, bradykinin, and carrageenan) were applied in the rat paw model, but the extract inhibited only the compound 48/80 elicited inflammation. The active extract was then fractionated by solvent-solvent partitioning and chromatographic methods with the guidance of the 48/80-induced anti-inflammatory assay, and the main compounds responsible for the activity were identified as ursolic acid and oleanolic acid. Our data suggest that the activity is most probably based on a membrane stabilizing effect caused by the inhibition of degranulation of mast cells. Moreover, previously unknown 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignans, nectandrin B, fragransin A2, and saucernetindiol were isolated and identified from H. rhamnoides for the first time.

Diterpene Constituents of Euphorbia exigua L. and Multidrug Resistance Reversing Activity of the Isolated Diterpenes.

Phytochemical investigation of the MeOH extract obtained from the aerial parts of the annual weed Euphorbia exigua L. resulted in the isolation of two novel (1, 2) and one known (3) jatrophane diterpenes. Their structures were established by extensive 1D‐ and 2D‐NMR spectroscopy and HR‐ESI‐MS. The isolated compounds were evaluated for multidrug resistance (MDR) reversing activity on human MDR gene‐transfected L5178 mouse lymphoma cells; and all three compounds were found to modulate the intracellular drug accumulation.

First phytochemical investigation of secondary metabolites of Euphorbia davidii Subils. and antiproliferative activity of its extracts.

The present work is the first phytochemical investigation of Euphorbia davidii Subils. After multistep separation process, three flavonoid glycosides were obtained from the ethyl acetate soluble fraction of the methanol extract of the whole plant. The structures of the isolated compounds were determined as kaempferol 3-O-rhamnoside, myricetin 3-O-rhamnoside, and quercetin 3-O-rhamnoside. Aqueous and organic extracts of the plant were screened in vitro for antiproliferative activity against HeLa (cervix epithelial adenocarcinoma), A431 (skin epidermoid carcinoma), A2780 (ovarian carcinoma) and MCF7 (breast epithelial adenocarcinoma) cells, using the MTT assay. n-Hexane and chloroform extracts demonstrated moderately dose-dependent cell growth inhibitory activity against all four cell lines.

Bioactive Segetane, Ingenane, and Jatrophane Diterpenes from Euphorbia taurinensis

A novel segetane (1: ) and jatrophane diterpene (2: ), together with five known diterpenoids possessing segetane (3: ), jatrophane (4: ), and ingenane skeletons (5 - 7: ), were isolated from the methanol extract of Euphorbia taurinensis All. The structure elucidation of the compounds was performed by means of extensive spectroscopic analysis, including HRESIMS and 1D (1H, J-modulated spin-echo carbon experiment) and 2D (HSQC, HMBC, COSY, NOESY) NMR experiments. The multidrug resistance reversing and cytotoxic effects of five diterpenes (1, 4:  - 7: ) were studied on the L5178 mouse lymphoma cell line using rhodamine 123 accumulation and the MTT cell viability assay. Segetane and jatrophane diterpenes had no cytotoxic activity on the sensitive parent and multidrug resistance cells, while ingenane diterpenes showed a cytotoxic effect on both cell lines. Ingenanes 6: and 7: and segetane 1: demonstrated the remarkable multidrug resistance modulating effect at 20 µM.