Human intestinal microbiota derived metabolism signature from a North American native botanical Oplopanax horridus with UPLC/Q-TOF-MS analysis.

Oplopanax horridus, widely distributed in North America, is an herbal medicine traditionally used by Pacific indigenous peoples for various medical conditions. After oral ingestion, constituents in O. horridus extract (OhE) could be converted to their metabolites by the enteric microbiome before absorption. In this study, in order to mimic gut environment, the OhE was biotransformed using the enteric microbiome of healthy human subjects. For accurate and reliable data collection with optimized approaches in sample preparation and analytical conditions, ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry were used to characterize parent constituents and their metabolites. In the extract, 20 parent compounds were identified including polyynes, sesquiterpenes, monoterpeondids, phenylpropanoids and phenolic acids. After the biotransformation, a total of 78 metabolites were identified, of which 37 belonged to polyynes metabolites. The common biotransformation pathways are hydroxylation, acetylization, methylation and demethylation. Based on the pathway distributions, the metabolism signature of OhE has been explored. The metabolism pathways of OhE compounds are dependent on their structural classifications and hydrophilic/hydrophobic properties. In summary, with comprehensive analysis, we systematically investigated human microbiome-derived OhE metabolites. The enteric microbial metabolism signature provides novel information for future effective use of O. horridus.

A Survey of Marine Natural Compounds and Their Derivatives with Anti-cancer Activity Reported in 2012.

Although considerable effort and progress has been made in the search for new anticancer drugs and treatments in the last several decades, cancer remains a major public health problem and one of the major causes of death worldwide. Many sources, including plants, animals, and minerals, are of interest in cancer research because of the possibility of identifying novel molecular therapeutics. Moreover, structure-activity-relationship (SAR) investigations have become a common way to develop naturally derived or semi-synthetic molecular analogues with improved efficacy and decreased toxicity. In 2012, approximately 138 molecules from marine sources, including isolated compounds and their associated analogues, were shown to be promising anticancer drugs. Among these, 62% are novel compounds. In this report, we review the marine compounds identified in 2012 that may serve as novel anticancer drugs.

A survey of marine natural compounds and their derivatives with anti-cancer activity reported in 2011.

Cancer continues to be a major public health problem despite the efforts that have been made in the search for novel drugs and treatments. The current sources sought for the discovery of new molecules are plants, animals and minerals. During the past decade, the search for anticancer agents of marine origin to fight chemo-resistance has increased greatly. Each year, several novel anticancer molecules are isolated from marine organisms and represent a renewed hope for cancer therapy. The study of structure-function relationships has allowed synthesis of analogues with increased efficacy and less toxicity. In this report, we aim to review 42 compounds of marine origin and their derivatives that were published in 2011 as promising anticancer compounds.

Cytotoxicity and Preliminary Analysis of the Pro-apoptotic and Cell Cycle Arrest Effects of Lantana ukambensis Against Colorectal Cancer Cells.

Lantana ukambensis (Vatke) Verdc. (Verbenaceae) is a seasonal herb widely spread in the West African region. The whole plant is used for the treatment of wounds, infections, and inflammatory pathologies. The purpose of this research is to evaluate the cytotoxicity and to analyze the probable pro-apototic, and cell cycle arrest effects of L. ukambensis methylene chloride extract and its fractions against HCT-116 and HT-29 colorectal cancer cells using preliminary tests in order to highlight the interest of this plant in the search of new anticancer molecules. The dried powder of the whole plant was extracted by methylene chloride maceration for 24 hours and the extract was divided into five fractions. The cytotoxicity of the crude extract and fractions were evaluated by the MTS assay. The most active fractions were subjected to some preliminary assays including crystal violet, Hoechst staining, cell cycle arrest, and annexin V/PI assays on the cancer cells to highlight the probable mechanism of action of these fractions. The methylene chloride, ethyl acetate, and 1-butanol fractions of L. ukambensis crude extract demonstrated significant antiproliferative effects on HCT-116 and HT-29 cell growth with IC50 values ranging between 2 to 15 µg/mL. 1-butanol and ethyl acetate fractions decreased the G1 phase by 20.53% and 28.47% and increased the G2/M by 23.47% and 25.90% respectively on HCT-116. Moreover, 1-butanol fraction increased the cumulative value of apoptotic cells by 49.77% on HCT-116 and ethyl acetate fraction increased this value by 53.37% at 15 µg/mL after 48 hours of exposure. The outcome of this study suggests the potential of 1-butanol and ethyl acetate fractions for the isolation of anticancer molecules against colorectal cancer.

4α-Methylated steroids with cytotoxic activity from the soft coral Litophyton mollis.

Seven new (1-3, 5 and 8-10) and three previously reported (4, 6 and 7) 4α-methylated steroids were isolated from the organic extract of the gorgonian Litophyton mollis. The structures and the relative configurations of the isolated natural products were determined on the basis of extensive analyses of their NMR and MS data. Metabolites 1 and 5-8 exhibited cytotoxic activity against K562 human chronic myelogenous leukemia cells with IC50 values below 10µM, while at the same time displaying low toxicity against healthy PBMCs.

Indigenous knowledge of medicinal plants among Dozo hunters: an ethnobotanical survey in Niamberla village, Burkina Faso.

OBJECTIVES: This investigation aims to provide a database of Dozo traditional knowledge of medicinal plants used for the treatment of common diseases. DESIGN: The study was conducted through individual interviews using a survey form. Data were recorded in a database allowing statistical analysis. Each plant was recorded and documented with a herbarium specimen. Settings/Location & Subjects: The term Dozo refers to great hunters from Burkina Faso, highly renowned for their knowledge of medicinal plants. Niamberla village was founded by Dozo hunters and is currently the residence of many traditional healers. Unfortunately, their indigenous knowledge is not well recorded and may be lost between two generations. RESULTS: A total of 16 traditional healers were interviewed, giving 89 recipes for the treatment of 37 diseases. The most common diseases are malaria (13%), psychological/spiritual issues (12%), gastric disorders (11%), sexually transmitted diseases (10%), and wounds (8%). A total of 56 medicinal plants have been identified, consisting mostly of trees (44%), shrubs (34%), and herbs (16%). CONCLUSIONS: The results of this research provide a basis for pharmacological and toxicological investigations and are necessary to preserve the indigenous knowledge of traditional medicine among Dozo hunters.

Cytotoxic, Antiproliferative and Pro-Apoptotic Effects of 5-Hydroxyl-6,7,3',4',5'-Pentamethoxyflavone Isolated from Lantana ukambensis.

Lantana ukambensis (Vatke) Verdc. is an African food and medicinal plant. Its red fruits are eaten and highly appreciated by the rural population. This plant was extensively used in African folk medicinal traditions to treat chronic wounds but also as anti-leishmanial or cytotoxic remedies, especially in Burkina Faso, Tanzania, Kenya, or Ethiopia. This study investigates the in vitro bioactivity of polymethoxyflavones extracted from a L. ukambensis as anti-proliferative and pro-apoptotic agents. We isolated two known polymethoxyflavones, 5,6,7,3',4',5'-hexamethoxyflavone (1) and 5-hydroxy-6,7,3',4',5'-pentamethoxyflavone (2) from the whole plant of L. ukambensis. Their chemical structures were determined by spectroscopic analysis and comparison with published data. These molecules were tested for the anti-proliferative, cytotoxic and pro-apoptotic effects on human cancer cells. Among them, 5-hydroxy-6,7,3',4',5'-pentamethoxyflavone (2) was selectively cytotoxic against monocytic lymphoma (U937), acute T cell leukemia (Jurkat), and chronic myelogenous leukemia (K562) cell lines, but not against peripheral blood mononuclear cells (PBMCs) from healthy donors, at all tested concentrations. Moreover, this compound exhibited significant anti-proliferative and pro-apoptotic effects against U937 acute myelogenous leukemia cells. This study highlights the anti-proliferative and pro-apoptotic effects of 5-hydroxy-6,7,3',4',5'-pentamethoxyflavone (2) and provides a scientific basis of traditional use of L. ukambensis.

Flavonoid glycosides from Olax mannii: Structure elucidation and effect on the nuclear factor kappa B pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Olax mannii Oliv. (Olacaceae) is among the many medicinal plants used in Nigeria for the ethnomedicinal management of both cancer and inflammation. Such plants represent potential sources of innovative therapeutic agents for the treatment of cancer and other malignant disorders. While the majority of medicinal plants exert their anticancer effects by direct cytotoxicity on tumor cells, it is important that other mechanisms through which these plants can exhibit anticancer effects are investigated. Preliminary studies indicated that Olax mannii leaves are rich sources of novel flavonoid glycosides. The detailed chemistry as well the mechanisms through which these flavonoid constituents may exert their cancer chemo-preventive and therapeutic effects are, however, not yet investigated. AIM OF THE STUDY: The aim of this study is to carry out a detailed chemical investigation of Olax mannii leaves and the effects of the isolated constituents on the nuclear factor kappa B (NF-κB) pathway. MATERIALS AND METHODS: A methanol leaf extract was subjected to various chromatographic separations to achieve isolation of flavonoid glycosides and the structures of the isolated compounds were elucidated by a combination of 1D and 2D NMR and high resolution mass spectrometry. Biological activities were assessed by measurement of cellular viability and proliferation using quantitative IncuCyte videomicroscopy, trypan blue staining and by quantification of the number of metabolically active K562 cells based on quantitation of ATP. The effect of the compounds on the inhibition of the NF-κB pathway as well as toxicity towards peripheral blood mononuclear cells to evaluate differential toxicity was also assayed. RESULTS: Chemical investigation of the methanol leaf extract of the plant material led to the isolation of three new flavonoid triglycosides, kaempferol 3-O-[α-D-apiofuranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O-α-L-rhamnopyranoside (1), kaempferol 3-O-[ß-D-glucopyranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O-α-L-rhamnopyranoside (2), kaempferol 3-O-[ß-D-arabinopyranosyl-(1→4)-α-L-rhamnopyranoside]-7-O-α-L-rhamnopyranoside (3), in addition to fourteen known flavonoid glycosides (4-17). Of all the tested compounds, only compound 9 (kaempferol 3-O-α-L-rhamnopyranoside) exhibited promising and specific antiproliferative activity on human K562 chronic myelogenous leukemia cells and dose-dependently inhibited NF-κB transactivation. CONCLUSION: The presence of this flavonoid glycoside and derivatives may account for the reported efficacy of Olax mannii leaf extract in the ethnomedicinal management of cancer and inflammation.

Traditional West African pharmacopeia, plants and derived compounds for cancer therapy.

Traditional pharmacopeia is strongly involved in the continuous search for the well being of African populations. The World Health Organization (WHO) estimates that 80% of the population of developing countries relies on traditional medicine for their primary care needs. Medicinal plants are the major resource of this folk medicine where several species are used for the treatment of diseases with an inflammatory and/or infectious component as it is the case of old wounds, skin diseases and malfunctions affecting internal organs such as liver, lung, prostate and kidney. Many of these pathologies described by practitioners of traditional medicine have similarities with certain cancers, but the lack of training of many of these healers does not allow them to establish a link with cancer. However, ethnobotanical and ethnopharmacological surveys conducted by several researchers allowed to identify plants of interest for cancer treatment. Most scientific investigations on these plants demonstrated an anti-inflammatory or antioxidant effect, and sometimes, antiproliferative and cytotoxic activities against cancer cells were reported as well. The emergence of resistance to cancer chemotherapy has forced researchers to turn to natural products of plant and marine origin. In the West African sub-region, research on natural anti-cancer molecules is still in its infancy stage because of very limited financial resources and the scarcity of adequate technical facilities. However, several plants were investigated for their anticancer properties through north-south or south-south partnerships. In this review, we will review the role of West African traditional pharmacopeia in cancer treatment as well as medicinal plants with anti-cancer properties.