A Multivariate Approach to Ethnopharmacology: Antidiabetic Plants of Eeyou Istchee.

An ethnopharmacological metanalysis was conducted with a large database available on antidiabetic activities of plant foods and medicines from the northern boreal forest, which are traditionally used by the indigenous Cree of James Bay, Quebec, Canada. The objective was to determine which bioassays are closely associated with the traditional knowledge of the Cree and which pharmacological metrics and phytochemical signals best define these plants and their groups. Data from 17 plant species, ethnobotanically ranked by syndromic importance value for treatment of 15 diabetic symptoms, was used along with 49 bioassay endpoints reported across numerous pharmacological studies and a metabolomics dataset. Standardized activities were separated into primary, secondary and safety categories and summed to produce a Pharmacological Importance Value (PIV) in each of the three categories for each species. To address the question of which pharmacological metrics and phytochemical signals best define the CEI anti-diabetes plants, multivariate analyses were undertaken to determine groupings of plant families and plant parts. The analysis identified Larix larcina as the highest PIV species in primary assays, Salix planifolia in secondary assays, and Kalmia angustifolia in safety assays, as well as a ranking of other less active species by PIV. Multivariate analysis showed that activity in safety PIV monitored mainly with cytochrome P450 inhibition patterns best reflected patterns of traditional medicine importance in Cree traditional knowledge, whereas potent primary bioactivities were seen in individual plants determined to be most important to the Cree for anti-diabetes purposes. In the secondary anti-diabetes assays, pharmacological variability was better described by plant biology, mostly in terms of the plant part used. Key signal in the metabolomics loadings plots for activity were phenolics especially quercetin derivatives. Traditional Indigenous knowledge in this analysis was shown to be able to guide the identification of plant pharmacological qualities in scientific terms.

Biochemometric Analysis of Fatty Acid Amide Hydrolase Inhibition by Echinacea Root Extracts.

Recent research demonstrates that Echinacea possesses cannabimimetic activity with potential applications beyond common contemporary uses for relief of cold and flu symptoms. In this study, we investigated the in vitro inhibitory effect of root extracts of Echinacea purpurea and Echinacea angustifolia on fatty acid amide hydrolase, the main enzyme that degrades the endocannabinoid anandamide. The objective was to relate variation in bioactivity between commercial Echinacea genotypes to their phytochemical profiles and to identify determinants of activity using biochemometric analysis. Forty root extracts of each of species were tested for inhibition of fatty acid amide hydrolase and analyzed by HPLC-DAD/MS to identify and quantitate alkylamides and caffeic acid derivatives. Fatty acid amide hydrolase inhibition ranged from 34 - 80% among E. angustifolia genotypes and from 33 - 87% among E. purpurea genotypes. Simple linear regression revealed the caffeic acid derivatives caftaric acid and cichoric acid, and the alkylamide dodeca-2E,4Z-diene-8,10-diynioc acid 2-methylbutylamide, as the strongest determinants of inhibition in E. purpurea (r* = 0.53, 0.45, and 0.20, respectively) while in E. angustifolia, only CADs were significantly associated with activity, most notably echinacoside (r* = 0.26). Regression analysis using compound groups generated by hierarchical clustering similarly indicated that caffeic acid derivatives contributed more than alkylamides to in vitro activity. Testing pure compounds identified as determinants of activity revealed cichoric acid (IC50 = 45 ± 4 µM) and dodeca-2E,4E,8Z,10E-tetraenoic acid isobutylamide (IC50 = 54 ± 2 µM) as the most active. The results suggest that several phytochemicals may contribute to Echinacea's cannabimimetic activity and that ample variation in genotypes exists for selection of high-activity germplasm in breeding programs.

A combination of (+)-catechin and (-)-epicatechin underlies the in vitro adipogenic action of Labrador tea (Rhododendron groenlandicum), an antidiabetic medicinal plant of the Eastern James Bay Cree pharmacopeia.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhododendron groenlandicum (Oeder) Kron & Judd (Labrador tea) was identified as an antidiabetic plant through an ethnobotanical study carried out with the close collaboration of Cree nations of northern Quebec in Canada. OBJECTIVES: In a previous study the plant showed glitazone-like activity in a 3T3-L1 adipogenesis bioassay. The current study sought to identify the active compounds responsible for this potential antidiabetic activity using bioassay guided fractionation based upon an in vitro assay that measures the increase of triglycerides content in 3T3-L1 adipocyte. MATERIALS AND METHODS: Isolation and identification of the crude extract's active constituents was carried out. The 80% ethanol extract was fractionated using silica gel column chromatography. Preparative HPLC was then used to isolate the constituents. The identity of the isolated compounds was confirmed by UV and mass spectrometry. RESULTS: Nine chemically distinct fractions were obtained and the adipogenic activity was found in fraction 5 (RGE-5). Quercetins, (+)-catechin and (-)-epicatechin were detected and isolated from this fraction. While (+)-catechin and (-)-epicatechin stimulated adipogenesis (238±26% and 187±21% relative to vehicle control respectively) at concentrations equivalent to their concentrations in the active fraction RGE-5, none afforded biological activity similar to RGE-5 or the plant's crude extract when used alone. When cells were incubated with a mixture of the two compounds, the adipogenic activity was close to that of the crude extract (280.7±27.8 vs 311± 30%). CONCLUSION: Results demonstrate that the mixture of (+)-catechin and (-)-epicatechin is responsible for the adipogenic activity of Labrador tea. This brings further evidence for the antidiabetic potential of R. groenlandicum and provides new opportunities to profile active principles in biological fluids or in traditional preparations.

Adipogenic Activity of Wild Populations of Rhododendron groenlandicum, a Medicinal Shrub from the James Bay Cree Traditional Pharmacopeia.

The traditional medicinal plant, Labrador tea (Rhododendron groenlandicum (Oeder) Kron & Judd; Ericaceae), present in the pharmacopoeia of the Cree of Eeyou Istchee, has shown glitazone-like activity in the 3T3-L1 adipogenesis bioassay. This activity has been attributed to phenolic compounds, which have been shown to vary in this plant as a function of insolation parameters. The goal of this study was to determine if these changes in phenolic content were pharmacologically significant. Leaves were harvested in 2006 throughout the James Bay region of Northern Quebec and ethanol extracts were tested in vitro using the 3T3-L1 murine cell line adipogenesis bioassay. This traditional medicinal plant was found active in the assay. However, there was no detectable spatial pattern in the accumulation of intracellular triglycerides, suggesting that such patterns previously observed in the phenolic profile of Labrador tea were not pharmacologically significant. Nonetheless, a reduction in the adipogenic activity was observed and associated with higher concentrations of quercetin for which selected environmental variables did not appropriately explain its variation.

Ethnobotanical study of medicinal plants by population of Valley of Juruena Region, Legal Amazon, Mato Grosso, Brazil.

ETHNOPHARMACOLOGICAL IMPORTANCE: The use of medicinal plants for treatment, cure and prevention of diseases has been described by many people since time immemorial. Because of this use, commercial and scientific interests have emerged, making it necessary to realize ethnobotanical surveys of medicinal plants species, which is important for subsequent chemical and pharmacological bioprospections. AIM OF THE STUDY: This study aimed at surveying, identifying, cataloging and documenting the medicinal plants species used in the Valley of Juruena, Northwestern Mato Grosso, Legal Amazon Brazil for the treatment of various human diseases, as well as assessed the species of interest for bioprospecting potential. MATERIALS AND METHODS: Informants were interviewed using semi-structured form to capture information on socio-demographic and ethnopharmacological data of medicinal plants such as vernacular name, uses, geographic origin, habit, form of preparation and part used. Results were analyzed using descriptive and quantitative means: indices of use-report (Ur) and informant consensus factor (ICF), for the selection of plant species with therapeutic potential. RESULTS: Three hundred and thirty two (332) plants species belonging to 90 families were reported for medicinal purposes and totaling 3973 use-reports were reported by 365 (92.9%) of the people interviewed. Asteraceae (32.2%), Fabaceae (26.7%) and Lamiaceae (24.4%) families were the most represented, with majority being species native (64.45%) to Brazil. Leaves (64.5%) were the part of the plant most used and infusion (45.7%) was the most utilized form. Gastrointestinal disorders followed by respiratory complaints topped the list of use-reports. The native or naturalized plants with the highest use reports in the order of decreasing absolute frequency per each emic-category are Cymbopogon citratus (DC.) Stapfc (104), Mentha pulegium L. (94), Arrabidaea chica (Humb. & Bonpl.) B. Verl. (97), Alternanthera brasiliana (L.) Kuntze (71), Baccharis crispa Spreng (57), Phyllanthus niruri L. (48), Gossypium barbadense L. (44), Solidago microglossa DC. (40) and Bauhinia forficata L. (20). And the most cited exotics are: Chenopodium ambrosioides L. (151), Aloe vera (L.) Burm. f., (89) and Rosmarinus officinalis L. (72). In some cases, high ICF values were found, which reflects high degree of homogeneity of consensus among informants in this region on medicinal plants. CONCLUSION: The population of Valle of Juruena makes use of a wide array of medicinal plants distributed in all use categories with predominance of those use in the treatments of gastrointestinal and respiratory ailments. The therapeutic potential of some of the species of medicinal importance extensively utilized by the population of the region have been scientifically validated, and are therefore promising prototype of new drugs. However, there are some of these species whose ethnomedicinal uses are yet to be scientifically verified and thus constitute an unexplored terrain for future biological/pharmacological studies.