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Endophytic fungi, being a prolific source of bioactive secondary metabolites, are of great interest for natural product discovery.Isolation and partial characterization of endophytic fungi inhabiting the leaves and woody parts of Taxus fuana Nan LiR.R. Mill. (Taxaceae) and evaluation of biological activity.Endophytic fungal isolates were identified by molecular analysis of internal transcribed spacer (ITS) regions of 18S rDNA. Extracts of the endophytic fungi cultured on potato dextrose agar and modified medium were evaluated using cancer chemoprevention bioassays [inhibition of TNF-α-induced NFκB, aromatase and inducible nitric oxide synthase (iNOS); induction of quinone reductase 1 (QR1)] and growth inhibition with MCF-7 cells.Nine of 15 fungal isolates were identified as belonging to Epicoccum, Mucor, Penicillium, Chaetomium, Paraconiothriym, Plectania or Trichoderma. Five of the 15 extracts inhibited NFκB activity (ICThe endophytic fungi studied are capable of producing pharmacologically active natural compounds. In particular, isolates derived from the wood of Taxus fuana should be prioritized for the isolation and characterization of bioactive constituents.

Natural products are a very productive source of leads for the development of medicines. Six Pakistani plants were chosen for study based on ethnobotanical data.Exploration of important medicinal plants of Pakistan for cancer treatment.The crude extracts of the six plants and their fractions were tested for inhibition of nuclear factor κB (NFκB), aromatase, and nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells, induction of quinone reductase 1 (QR1), agonism of retinoid X receptor, and growth inhibition with MCF-7, LU-1 and MDA-MB-231 cancer cells.Two samples of Withania coagulans (Stocks) Dunal (Solanaceae) demonstrated inhibition of TNF-α induced activity of NFκB with IC₅₀ values of 2.6 and 4.3 µg/mL, respectively. Two fractions from W. coagulans and Euphorbia wallichii Hook F. (Euphorbiaceae) aerial parts inhibited aromatase with IC₅₀ values of 17.0 and 17.7 µg/mL, respectively. A total of 13 samples (five from E. wallichii, one from Acer oblongifolium Hort. ex Dippel (Aceraceae), one from Aster thomsonii C. B. Clarke (Asteraceae) and six from W. coagulans aerial parts with fruits) inhibited NO production with IC₅₀ values ranging from 1.3 to 15.6 µg/mL. Fourteen samples demonstrated induction of QR1 with CD ranging from 1.0 to 20.6 µg/mL, and a total of eight extracts and fractions inhibited the proliferation of cancer cells in culture with IC₅₀ values ranging from 1.2 to 7.8 µg/mL.Selected plants can be a valuable source of chemopreventive and anticancer products. W. coagulans aerial parts showed the strongest activity.

Whether natural product drug discovery programs should rely on wild plants collected "randomly" from the natural environment, or whether they should also include plants collected on the basis of use in traditional medicine remains an open question.This study analyzes whether plants with ethnomedical uses from Vietnam and Laos have a higher hit rate in bioassay testing than plants collected from a national park in Vietnam with the goal of maximizing taxonomic diversity ("random" collection).All plants were extracted and subjected to bioassay in the same laboratories. Results of assays of plant collections and plant parts (samples) were scored as active or inactive based on whether any extracts had a positive result in a bioassay. Contingency tables were analyzed using χ(2) statistics.Random collections had a higher hit rate than ethnomedical collections, but for samples, ethnomedical plants were more likely to be active. Ethnomedical collections and samples had higher hit rates for tuberculosis, while samples, but not collections, had a higher hit rate for malaria. Little evidence was found to support an advantage for ethnomedical plants in HIV, chemoprevention and cancer bioassays. Plants whose ethnomedical uses directly correlated to a bioassay did not have a significantly higher hit rate than random plants.Plants with ethnomedical uses generally had a higher rate of activity in some drug discovery bioassays, but the assays did not directly confirm specific uses.Ethnomedical uses may contribute to a higher rate of activity in drug discovery screening.

The western Himalayas in the northern areas of Pakistan have significant potential for ethnomedicinal research. In the current study, indigenous informants were interviewed using open-ended questionnaires and a free-listing of knowledge related to native medicinal plants. Information patterns indicated that over 100 local plant species were in frequent medicinal use for a variety of conditions, including inflammation and cancer. Several field surveys were conducted in community forests and meadows, with the aim of exploration, collection, taxonomic identification, and finally, in vitro analysis. Organic extracts of eight species were tested for inhibition of nuclear factor-kappaB (NF-κB), activation of retinoic acid X receptor alpha (RXR), induction of quinone reductase (QR), and inhibition of aromatase, along with assessment of cytotoxicity with four human cancer cell lines. Mellia azedarach, Ajuga bractiosa, Figonia cretica and Swertia chirata inhibited both tetradecanoylphorbol-13-acetate (TPA) and tum...

The paw paw tree, Asimina triloba. (L.) Dunal (Annonaceae), contains more than 50 bioactive components, primarily annonaceous acetogenins. Some therapeutic activities have been associated with this material, but the potential to mediate a cancer chemopreventive effect has not been reported. In this study, a standardized extract from the twigs, in which bullatacin, asimicin, and trilobacin represent the most potent and major bioactive acetogenins, was tested in the N.-methyl-N.-nitrosourea–induced mammary carcinogenesis model. With Sprague-Dawley rats given a diet containing paw paw extract (1250 and 2500 mg/kg diet; based on maximum tolerated dose studies), mammary tumor latency was increased from 55 to 66 days. However, mammary tumor incidence and multiplicity were not affected by extract consumption.

Salvia hypargeia. Fisch. et Mey. (Lamiaceae) root extract, among 16 Salvia. extracts, showed the highest activity against the human ovarian cancer cell line. Bioactivity-guided fractionation of this plant extract has yielded four abietane-type diterpenes [5,6-didehydro-7-hydroxytaxodone (1), 14-deoxycoleon U (= 6-hydroxysalvinolone) (2), demethylcryptojaponol (3), and salvicanaric acid (4)] two triterpenes (lupeol and lupeol-3-acetate), and a fatty acid mixture consisting mainly of palmitic acid (51.6%) and palmitoleic acid (6.4%). Compounds 2 and 3 were found to be active against A2780 human ovarian cancer cell line with IC50 values of 3.9 and 1.2 μ g/mL, respectively, and the fatty acid composition was the most active part of the extract (IC50 = 0.6 μ g/mL).

Given the high probability of developing cancer over the period of a normal life span, cancer chemoprevention provides an attractive therapeutic strategy for the delay or reversal of this process. ...

A new plant species, Barringtonia maunwongyathiae. W. Chuakul (Lecythidaceae), was recently discovered in Khuan Thon Forest, Ao Luek District, Krabi Province, Thailand. Chemical investigation of th...

Work has continued on the investigation of plants, collected mainly from tropical rainforests, as potential sources of new cancer chemotherapeutic agents. About 400 primary samples are obtained each year, with the chloroform-soluble extract of each being screened against a battery of in vitro assays housed at the three consortial sites in our current National Cooperative Drug Discovery Group (NCDDG) research project. An HPLC-MS dereplication procedure designed to screen out “nuisance” compounds has been refined. Several hundred secondary metabolites that are active in one or more of the primary assays utilized have been obtained in the project to date, and are representative of wide chemical diversity. Some of these are also active in various in vivo assays, inclusive of the hollow fiber assay, which was installed recently as part of our collaborative research effort. A number of bioactive compounds of interest to the project are described.

Japanese barberry (Berberis thunbergii DC.) is a species non-native to North America but widely found as a garden ornamental. Due to its invasiveness, it has become a pest in certain parts of Maine. A comparison of alkaloid content and antibacterial activity of Japanese barberry with common barberry (Berberis vulgaris L.) has been carried out to determine whether B. thunbergii might serve as a viable substitute for more commonly used berberine-containing medicinal plants such as goldenseal (HHydrastis canadensis L.)Extracts were prepared by exhaustively extracting B. thunbergii, B. vulgaris, and H. canadensis with 70% ethanol (ratio of roots to solvent was 1 : 5). Additional extracts were prepared with both 65% glycerin, and a mixture of 15% alcohol, 40% glycerin and 45% water (ratio of roots to solvent was 1 : 4).The ethanolic extracts were more potent against five bacteria than either the glycerin extracts or the mixed solvent extracts. Notably, the extracts exhibited strongest activity versus bacteria ...

Anti-inflammatory activity of a methanol extract of the leaves of Vochysia ferruginea Mart. (Vochysiaceae) was determined in the rat paw edema test. At doses of 250 and 500 mg/kg, i.p., the extract reduced edema significantly (p < 0.01) compared with indomethacin (10 mg/kg). It also showed significant dose-dependent analgesic activity (0.3–100 mg/kg) in mice (p < 0.05), compared with acetaminophen (130 mg/kg), and inhibitory activity with cyclooxygenase (COX-1) (72% at 70 mg/ml), compared with indomethacin (2.3 mM). An ulcerogenic effect was observed when the extract was administered to rats.

During a large-scale isolation of the cancer chemopreventive mammalian lignan precursor secoisolariciresinol diglucoside (SDG, 6) from the defatted meal of flaxseed (Linum usitatissimum L.), a new ...

Paulitin and isopaulitin were isolated from Ambrosia artemisiaefolia and evaluated for their cytotoxic and antimalarial activities. The relative configuration of dumosin was also established.

Ten diterpenoids [6a-hydroxysalvinolone (1), 6 alpha-hydroxytaxodone (2), aethiopinone (3), microstegiol (4). ferruginol (5), saprorthoquinone (6, 11,12-dioxoabieta-8,13-diene (7), taxodione (8), hypargenin A (9), hypargenin D (10)] and three triterpenoids [lupeol 3-acetate, delta-oleanol 3-acetate and beta-sitosterol] were isolated from the roots of Salvia hypargeia, a plant Endemic to Turkey. The crude extract and compounds 1-2, 5-10 were tested against a panel of human cancer cell lines [human breast cancer (BC 1), human lung cancer (LU 2), human colon cancer (COL 2), human epidermoidal carcinoma in mouth (KB), vinblastine-resistant ICB-VI, hormone-dependent human prostate cancer (LNCaP)] as well as P388 and ASK cells in culture. The crude extract was active in all of the rest systems, except KB. Isolates 1 and 8 were also found to mediate a generalized cytotoxic response.

The cytotoxic potential and structure activity relationships of several indole metabolites obtained from feeding experiments using Streptomyces staurosporeus, a staurosporine producer, are described. 6-Fluoro-tryptamine and N b -acetyl-tryptamine-5- O -a-L-rhamnopyranoside, a metabolite obtained from the feeding experiment, demonstrated greatest activity with KB cells in culture, by means of an unknown mechanism.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a naturally occurring compound shown to inhibit 7,12‐dimethylbenz[a]anthracene-induced preneoplastic lesions in mouse mammary organ culture and 12O-tetradecanoylphorbol-13-acetate-promoted mouse skin tumors. It has been postulated that resveratrol may inhibit tumorigenesis in mouse skin through interference with reactive oxidant pathways, and possibly by modulating the expression of c-fos and TGF-s1. The chemopreventive potential of resveratrol was further examined by investigating its effect on cyclooxygenase (COX) metabolites monitored by HPLC analysis. Resveratrol was found to inhibit the generation of arachidonic acid metabolites catalyzed by both COX-1 and COX-2. In addition, this compound significantly inhibited malignant transformation induced by chemical carcinogens in the mouse C3H10T1/2 cell culture system. These data serve to corroborate the cancer chemopreventive potential of resveratrol.

Cancer chemopreventive effects of organic extracts from 29 species of lichens collected in Iceland were evaluated using a panel of in vitro bioassays whereby extracts were tested for potential to induce quinone reductase (QR) and differentiation of human promyelocytic leukemia (HL-60) cells, inhibit cyclooxygenase-1 (COX-1), phorbol ester-induced ornithine decarboxylase (ODC), aromatase and sulfatase, as well as for antioxidant, estrogenic/anti-estrogenic and antiproliferative activity. In addition, the extracts were tested for cytotoxicity against 12 cancer cell lines. The most significant results were exhibited by extracts from Xanthoria elegans and Alectoria nigricans , which respectively, induced QR activity (concentration to double activity = 4.8 µg/ml) and inhibited phorbol ester-induced ODC activity with mouse 308 cells in culture (IC 50 = 2.6 µg/ml). Moderate inhibition of [ 3 H]thymidine incorporation with HL-60 cells was exhibited by the Peltigera leucophlebia extract. Several extracts prevented estrogen formation from estrogen precursors by inhibiting the enzymatic activities of aromatase ( Sphaerophorus globosus , Cetrariella delisei , Melanelia hepatizon ) and sulfatase ( Cladonia gracilis , Sphaerophorus fragilis , S. globosus ). None of the extracts demonstrated significant cytotoxic effects with selected cell lines.

(2002). Natural Compounds in Cancer Therapy. John Boik, Oregon Medical Press, Princeton, MN, 2001, $32.00 (ISBN 0-9648280-1-4) Pharmaceutical Biology: Vol. 40, No. 1, pp. 79-79.