Chemical Analysis and Antidiabetic Potential of a Decoction from Stevia serrata Roots.

A decoction of the roots (31.6-316 mg/kg) from Stevia serrata Cav. (Asteraceae) as well as the main component (5-150 mg/kg) showed hypoglycemic and antihyperglycemic effects in mice. The fractionation of the active extract led to the isolation of dammaradiene acetate (1), stevisalioside A (2), and three new chemical entities characterized by spectroscopic methods and named stevisaliosides B-D (3-5). Glycoside 2 (5 and 50 mg/kg) decreased blood glucose levels and the postprandial peak during oral glucose and insulin tolerance tests in STZ-hyperglycemic mice. Compounds 1-5 were tested also against PTP1B1-400 and showed IC50 values of 1180.9 ± 0.33, 526.8 ± 0.02, 532.1 ± 0.03, 928.2 ± 0.39, and 31.8 ± 1.09 µM, respectively. Compound 5 showed an IC50 value comparable to that of ursolic acid (IC50 = 30.7 ± 0.00 µM). Docking studies revealed that 2-5 and their aglycones bind to PTP1B1-400 in a pocket formed by the C-terminal region. The volatilome of S. serrata was characterized by a high content of (E)-longipinene, spathulenol, guaiadiene, seychellene, and aromandendrene. Finally, a UHPLC-UV method was developed and validated to quantify the content of 2 in the decoction of the plant.

Traditional knowledge of medicinal mushrooms and lichens of Yuman peoples in Northern Mexico.

BACKGROUND: Mushrooms and lichens are natural therapeutic resources whose millenary importance persists in indigenous and mestizo communities of Mexico. However, in this regard, in the northern part of the country there are few ethnobiological explorations. This study investigates the local knowledge of medicinal mushrooms and lichens used by Yuman peoples, whose native speakers are in imminent danger of extinction along with their biocultural heritage due to changes in their traditional primary activities and the usurpation of their ancestral lands. METHODS: Ethnographic techniques in the field and standard lichenological and mycological methods in the laboratory were used. RESULTS: Information was obtained on the medicinal use of 20 species, of which six are lichens of the genus Xanthoparmelia and 14 are non-lichenized fungi, mainly gasteroids. The latter are primarily used to treat skin lesions, while lichens are used in heart, urinary, and gastrointestinal diseases. The transmission of this local knowledge to future generations is discussed, as well as the intercultural cognitive convergence about the uses of medicinal mushrooms and lichens. CONCLUSIONS: The Yuman peoples preserve knowledge, practices and beliefs around mushrooms and lichens. Although increasingly less used, they still form part of their culinary and traditional medicine; even some are also used as ludic and ornamental purposes, and as trail markers. Beyond the pragmatic importance of these organisms, traditional knowledge about them is an essential part of the cultural identity that the Yuman peoples strive to preserve.

Antidiabetic Sterols from Peniocereus greggii Roots.

The roots of the cactus Peniocereus greggii, which grows in Northern Mexico and in the south of Arizona, are highly valued by the Pima to treat diabetes and other illnesses, such as breast pain and common cold. As part of our chemical and pharmacological investigation on medicinal plants used for treating diabetes, herein we report the hypoglycemic and antihyperglycemic action of a decoction prepared from the roots of the plant. The active compounds were a series of cholestane steroids, namely, peniocerol (2), desoxyviperidone (3), viperidone (4), and viperidinone (5). Also, a new chemical entity was obtained from an alkalinized chloroform extract (CE1), which was characterized as 3,6-dihydroxycholesta-5,8(9),14-trien-7-one (6) by spectroscopic means. Desoxyviperidone (3) showed an antihyperglycemic action during an oral glucose tolerance test. Compound 3 was also able to decrease blood glucose levels during an intraperitoneal insulin tolerance test in hyperglycemic mice only in combination with insulin, thus behaving as an insulin sensitizer agent. Nevertheless, mitochondrial bioenergetic experiments revealed that compounds 3 and 6 increased basal respiration and proton leak, without affecting the respiration associated with ATP production in C2C12 myotubes. Finally, an ultraefficiency liquid chromatographic method for quantifying desoxyviperidone (3) and viperidone (4) in the crude drug was developed and validated. Altogether, our results demonstrate that Peniocereus greggii decoction possesses a hypoglycemic and antihyperglycemic action in vivo, that sterols 2 and 6 promotes insulin secretion in vitro, and that desoxyviperidone (3) physiologically behaves as an insulin sensitizer agent by a mechanism that may involve mitochondrial proton leak.

Anti-Helicobacter pylori Activity of Artemisia ludoviciana subsp. mexicana and Two of Its Bioactive Components, Estafiatin and Eupatilin.

Artemisia ludoviciana subsp. mexicana has been traditionally used for the treatment of digestive ailments such as gastritis, whose main etiological agent is Helicobacter pylori. In a previous screening study, the aqueous extract exhibited a good in vitro anti-H. pylori activity. With the aim of determining the efficacy of this species as a treatment for H. pylori related diseases and finding bioactive compounds, its aqueous extract was subjected to solvent partitioning and the fractions obtained were tested for their in vitro anti-H. pylori effect, as well as for their in vivo gastroprotective and anti-inflammatory activities. The aqueous extract showed a MIC = 250 µg/mL. No acute toxicity was induced in mice. A gastroprotection of 69.8 ± 3.8%, as well as anti-inflammatory effects of 47.6 ± 12.4% and 38.8 ± 10.2% (by oral and topical administration, respectively), were attained. Estafiatin and eupatilin were isolated and exhibited anti-H. pylori activity with MBCs of 15.6 and 31.2 µg/mL, respectively. The finding that A. ludoviciana aqueous extract has significant anti-H. pylori, gastroprotective and anti-inflammatory activities is a relevant contribution to the ethnopharmacological knowledge of this species. This work is the first report about the in vivo gastroprotective activity of A. ludoviciana and the anti-H. pylori activity of eupatilin and estafiatin.

Production of Encecalin in Cell Cultures and Hairy Roots of Helianthella quinquenervis (Hook.) A. Gray.

Plant cell and organ cultures of Helianthella quinquenervis, a medicinal plant whose roots are used by the Tarahumara Indians of Chihuahua, Mexico, to relieve several ailments, were established to identify and quantify some chromenes with biological activity, such as encecalin, and to evaluate their potential for biotechnological production. Gas chromatography-mass spectrometry (GC-MS) analysis corroborated the presence of quantifiable amounts of encecalin in H. quinquenervis cell cultures (callus and cell suspensions). In addition, hairy roots were obtained through three transformation protocols (prick, 45-s sonication and co-culture), using wild type Agrobacterium rhizogenes A4. After three months, cocultivation achieved the highest percentage of transformation (66%), and a comparable production (FW) of encecalin (110 µg/g) than the sonication assay (120 µg/g), both giving far higher yields than the prick assay (19 µg/g). Stable integration of rolC and aux1 genes in the transformed roots was confirmed by polymerase chain reaction (PCR). Hairy roots from cocultivation (six months-old) accumulated as much as 1086 µg/g (FW) of encecalin, over three times higher than the cell suspension cultures. The production of encecalin varied with growth kinetics, being higher at the stationary phase. This is the first report of encecalin production in hairy roots of H. quinquenervis, demonstrating the potential for a future biotechnological production of chromenes.

Domestication of aromatic medicinal plants in Mexico: Agastache (Lamiaceae)-an ethnobotanical, morpho-physiological, and phytochemical analysis.

BACKGROUND: Most reports of domesticated plants that involve a domestication gradient or inter-specific hybridization in Mexico have focused on those used as food. This study provides knowledge about these processes in two aromatic medicinal plants, Agastache mexicana (Lamiaceae) and A. m. subsp. xolocotziana, widely used in Mexican traditional medicine for the treatment of gastrointestinal ailments and for their sedative effect. Different populations of A. mexicana along a gradient of domestication are found in the foothills of the Popocatepetl volcano of central Mexico, while in this same area the subsp. xolocotziana grows only in the cultivation, possibly a product of hybridization between A. mexicana and Agastache palmeri. This study links ethnobotanical, morpho-physiological, and phytochemical evidence to document the domestication of both taxa as well as elucidates the possible hybrid origin of the subsp. xolocotziana. METHOD: We analyze three groups of data derived from (1) 80 semi-structured interviews aimed at documenting the selection criteria related to the use and management of A. mexicana; (2) a cultivation experiment under homogeneous conditions, evaluating 21 floral, vegetative, and seed characters (that were important according to ethnobotanical information) in 97 plants corresponding to 13 populations of the taxa under study; and (3) the chemical profiles of the essential oils of these plants by means of a thin-layer chromatography. RESULTS: By linking the three types of evidence, two evolutionary processes are distinguished: (1) A. mexicana occurs in the encouraged-cultivated phases of the domestication gradient and (2) A. m. subsp. xolocotziana may have originated through inbreeding depression or hybridization. These two cultivated plants show a domestication syndrome based upon organoleptic differentiation due to their dissimilar phytochemical composition and gigantism in flowers, seeds, and rhizomes (the last enhancing their asexual reproductive capacity). In addition to this, A. mexicana exhibits more intense floral pigmentation and foliar gigantism while subsp. xolocotziana presents floral albinism and partial seed sterility. CONCLUSION: Two divergent evolutionary processes are reported for the domestication of A. mexicana as a result of the intensification of its use and management. The selection processes of these plants have resulted in alternation of the organoleptic properties based upon the divergence of the phytochemical composition. Also, gigantism has been selected in culturally preferred plant parts and in correlated structures. The preceding characteristics reinforce the joint use of these plants in infusion in Mexican traditionalmedicine for the treatment of gastrointestinal diseases and for their sedative effects.

Antinociceptive Potential of Zinnia grandiflora.

An aqueous extract prepared from the aerial parts of Zinnia grandiflora was found not to induce acute toxicity (LD50> 5g/kg, p.o.) in mice when tested by the Lorke method. This extract showed notable antinociceptive and anti-inflammatory actions when evaluated by the formalin- (ED50 = 224.62 ± 38.17 mg/kg, p.o.) and the carrageenan-induced paw edema models in mice, respectively. The organic-soluble fractions obtained by partitioning the infusion with CH2Cl2 and EtOAc were also active in the formalin test. The most important antinociceptive effect was observed with the CH2Cl2 fraction; extensive fractionation of the latter yielded three new elemanolides, namely, zinagranolides D-F (1-3), which were characterized structurally by spectroscopic means. The structure of compound 2 was established unequivocally by an X-ray crystallographic analysis. This compound exerted a significant antinociceptive effect in the formalin assay, better than that of diclofenac used as a positive control.

Molecular Markers Associated With Chemical Analysis: A Powerful Tool for Quality Control Assessment of Copalchi Medicinal Plant Complex.

The copalchi complex, Hintonia latiflora, H. standleyana, and Exostema caribaeum, is widely used in Mexico for treating diabetes and gastrointestinal disorders. The first therapeutic use for H. latiflora bark was registered in the "Florentine Codex" in the sixteenth century. The latest pharmacological and phytochemical studies revealed that the infusion of the leaves have hypoglycemic, antihyperglycemic and gastroprotective activities. For these reasons the monograph of the main copalchi species, H. latiflora, was recently added to the Mexican Herbal Pharmacopoeia. Nevertheless, quality control parameters are focused to the bark but not to the leaves. Moreover, information about other Rubiaceae species is needed. The main goal of this study was to generate molecular and chemical markers for quality control of the copalchi complex raw material. In addition, the resolution of the taxonomical ambiguity between H. latiflora and H. standleyana, as well as the testing of the molecular and chemical markers in different geographical batches, were aims of this study. The molecular markers and chemical profiles of the leaf infusions were generated considering three different populations for H. latiflora and separate individuals of the three species (HL, n = 10; HS, n = 3; EC, n = 4). The molecular markers matK, rbcL, trnH-psbA, rpl32-trnL, and ITS2 were tested for their discriminating capabilities. Chemical profiles of the leaf infusions were obtained by means of HPLC analyses using chlorogenic acid and 4-phenylcoumarins as chemical markers. The concatenated sequence of the molecular markers trnH-psbA, rpl32-trnL, and ITS2 clearly distinguished the three taxa, clarifying the taxonomical ambiguity of the Hintonia genus. Additionally, the chemical profiles allowed the unequivocal identification of each species supporting the molecular results; the geographical origin of the samples did not modify neither the chemical profiles nor the concatenated sequence of H. latiflora, suggesting that it is a robust identity test. The complementary use of molecular and chemical markers will assure the quality of plant material used in traditional medicine for therapeutic purposes, and should be valuable new information for the National Health authorities as a part of the Mexican Herbal Pharmacopoeia.

α-Glucosidase Inhibitors from Salvia circinata.

A dried infusion prepared from the aerial parts of Salvia circinata did not provoke acute toxicity in mice (LD50 > 5 g/kg). This infusion showed poor hypoglycemic and antihyperglycemic effects (100-570 mg/kg) when tested in normal and hyperglycemic mice using acute and oral glucose tolerance tests, respectively. However, this infusion possessed antihyperglycemic action in vivo during an oral sucrose tolerance test (31.6-316 mg/kg), suggesting the presence of α-glucosidase inhibitors in S. circinata. Fractionation of a nonpolar extract of the aerial parts of the plant yielded a new biflavone (1) and four new neoclerodane diterpenoid glucosides (2-5) along with the known compounds amarisolide (6), pedalitin (7), apigenin-7-O-ß-d-glucoside (8), and the flavone 2-(3,4-dimethoxyphenyl)-5,6-dihydroxy-7-methoxy-4H-chromen-4-one (9). Compounds 1 and 6-9 were active against mammalian α-glucosidases; 6 and 7 were also active against a recombinant α-glucosidase from Ruminococcus obeum and reduced significantly the postprandial peak during an oral sucrose tolerance test in healthy mice, consistent with their α-glucosidase inhibitory activity. Molecular docking and dynamic studies revealed that compounds 6 and 7 might bind to α-glucosidases at the catalytic center of the enzyme.

Anti-Hyperglycemic Activity of Major Compounds from Calea ternifolia.

Demethylisoencecalin (1) and caleins A (4) and C (5) (3.16-31.6 mg/kg, p.o.), the major components from an infusion of Calea ternifolia controlled postprandial glucose levels during an oral sucrose tolerance test (OSTT, 3 g/kg) in normal and nicotinamide/streptozotocin (NA/STZ, 40/100 mg/kg) hyperglicemic mice. The effects were comparable to those of acarbose (5 mg/kg). During the isolation of 1, 4, and 5, four additional metabolites not previously reported for the plant, were obtained, namely 6-acetyl-5-hydroxy-2-methyl-2-hydroxymethyl-2H-chromene (3), herniarin (6), scoparone (7), and 4',7-dimethylapigenin (8). In addition, the structure of calein C (5) was confirmed by X-ray analysis. Pharmacological evaluation of the essential oil of the species (31.6-316.2 mg/kg, p.o.) provoked also an important decrement of blood glucose levels during an OSTT. Gas chromatography coupled with mass spectrometry (GC-MS) analysis of the headspace solid phase microextraction (HS-SPME)-adsorbed compounds and active essential oil obtained by hydrodistillation revealed that chromene 1 was the major component (19.92%); sesquiterpenes represented the highest percentage of the essential oil content (55.67%) and included curcumene (7.10%), spathulenol (12.95%) and caryophyllene oxide (13.0%). A suitable High Performance Liquid Chromatography (HPLC) method for quantifying chromenes 1 and 6-hydroxyacetyl-5-hydroxy-2,2-dimethyl-2H-chromene (2) was developed and validated according to standard protocols.

Spasmolytic Action of Preparations and Compounds from Hofmeisteria schaffneri.

Hofmeisteria schaffneri is used in Mexican folk medicine for treating painful gastric complaints. Therefore, in this paper the smooth muscle relaxant effect of the essential oil, and an infusion of the whole plant were evaluated using the gastrointestinal transit test in mice. The results revealed that both preparations at 316 mg/kg inhibited gastrointestinal transit by 47.5 and 52.1%, respectively. The common component of the infusion and essential oil was 8.9 -epoxy-10-acetoxythymol angelate (2), which inhibited the gastrointestinal transit by 53.4% at a dose of 31.6 mg/kg. An HPLC-UV method was developed and validated to quantify 2. The chromatographic conditions were: A LiChrospher® 100 RP-18 column (250 x 4 mm i.d., 5µm) with a mobile phase composed of CH3CN-H2O, in a gradient run at a flow rate of 0.6 mL/min, using a wavelength of 215 nm. The method was linear, precise, accurate, and showed excellent recovery. According to the results, compound 2 can be used as a marker for the quality control procedures of the crude drug of H. schaffneri.

Mexican Arnica (Heterotheca inuloides Cass. Asteraceae: Astereae): Ethnomedical uses, chemical constituents and biological properties.

ETHNOPHARMACOLOGICAL RELEVANCE: Heterotheca inuloides Cass. (Asteraceae) has been traditionally used to treat a wide range of diseases in Mexico in the treatment of rheumatism, topical skin inflammation, muscular pain colic, and other painful conditions associated with inflammatory processes, additionally has been used to treat dental diseases, and gastrointestinal disorders. This species has also been used for the treatment of cancer and diabetes. This review provides up-to-date information on the botanical characterization, traditional uses, chemical constituents, as well as the biolological activities of H. inuloides. MATERIAL AND METHODS: A literature search was conducted by analyzing the published scientific material. Information related to H. inuloides was collected from various primary information sources, including books, published articles in peer-reviewed journals, monographs, theses and government survey reports. The electronic search of bibliographic information was gathered from accepted scientific databases such as Scienfinder, ISI Web of Science, Scielo, LILACS, Redalyc, Pubmed, SCOPUS and Google Scholar. RESULTS: To date, more than 140 compounds have been identified from H. inuloides, including cadinane sesquiterpenes, flavonoids, phytosterols, triterpenes, benzoic acid derivatives, and other types of compounds. Many biological properties associated with H. inuloides. Many studies have shown that the extracts and some compounds isolated from this plant exhibit a broad spectrum of biological activities such as antioxidant, antitumor, anti-inflammatory, cytotoxic, and chelating activities, as well as insecticidal and phytotoxic activity. To date, reports on the toxicity of H. inuloides are limited. CONCLUSIONS: A comprehensive analysis of the literature obtained through the above-mentioned sources confirmed that ethnomedical uses of H. inuloides have been recorded in Mexico to treat rheumatism, pain, and conditions associated with inflammatory processes. Pharmacological studies have demonstrated the activity of certain compounds associated with the traditional use of the plant such as the anti-inflammatory and cytotoxic activities of the species. The available literature showed that cadinene sesquiterpenes are the major bioactive components of H. inuloides with potential pharmacological activities. Further investigations are needed to fully understand the mode of action of the major active constituents.

Antidiabetic and Antihyperalgesic Effects of a Decoction and Compounds from Acourtia thurberi.

The purpose of this research was to examine the preclinical efficacy of a decoction from the roots of Acourtia thurberi as a hypoglycemic, antihyperglycemic, and antihyperalgesic agent using well-known experimental models in mice. Acute oral administration of A. thurberi decoction did not produce toxic effects in mice, according to the Lorke procedure. A. thurberi decoction (31.6-316.2 mg/kg, p. o.) decreased blood glucose levels during acute hypoglycemic and the oral glucose tolerance and oral sucrose tolerance tests, both in normoglycemic and hyperglycemic animals. Phytochemical analysis of A. thurberi roots led to the isolation of perezone (1), a mixture of α-pipitzol (2) and ß-pipitzol (3), and 8-ß-D-glucopyranosyloxy-4-methoxy-5-methyl-coumarin (4). A pharmacological evaluation of compounds 1-4 (3.2-31.6 mg/kg) using the same assays revealed their hypoglycemic and antihyperglycemic actions. Finally, local administration of A. thurberi decoction (31.6-316.2 µg/paw) and compounds 1-4 (3.2-31.6 µg/paw) produced significant inhibition on the licking time during the formalin test in healthy and hyperglycemic mice, demonstrating their antinociceptive and antihyperalgesic potential, respectively. Altogether, these results could be related to the use of A. thurberi for treating diabetes and painful complaints in contemporary Mexican folk medicine. A suitable UPLC-ESI/MS method was developed and successfully applied to quantify simultaneously compounds 1 and 4 in A. thurberi decoction.

Antinociceptive activity of the essential oil from Artemisia ludoviciana.

ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Artemisia ludoviciana are widely used in Mexico for treating gastrointestinal disorders, painful complaints and diabetes. AIM OF THE STUDY: To establish the preclinical efficacy as antinociceptive agent of the essential oil (EO) from the aerial parts of A. ludoviciana using well-known animal models. MATERIALS AND METHODS: Acute antinociceptive effect of EO (1, 10, 31.6, 100, and 316mg/kg, i.p.) was evaluated using the hot plate and paw formalin models in mice. The motor effects were assessed with the rota-rod and open field assays. The volatile components obtained by headspace solid phase microextraction (HS-SPME) and hydrodistillation were determined using gas chromatography coupled with mass spectrometry (GC-MS) analysis. RESULTS: EO decreased first and second phases of formalin test; in the first stage, the better effect was obtained with the treatment of 316mg/kg but in the second phase, time licking was attenuated at the doses of 31.6, 100 and 316mg/kg. The effectiveness of EO (ED50=25.9mg/kg) for attenuating neurogenic pain was corroborated using the hot plate test. The antinociceptive action of EO was blocked by naloxone suggesting that its mode of action involved an opioid mechanism. Furthermore, EO (316mg/kg) did not affect animal motor and coordination functions when tested by the rota-rod and open field tests. The latter results indicated that the pharmacological effects exerted by EO during the hot plate and formalin test are truly antinociceptive. GC-MS analysis of EO revealed that (±)-camphor, γ-terpineol, 1,8-cineole and borneol were the major volatile compounds of the plant. CONCLUSION: EO from A. ludoviciana showed significant antinociceptive effect, which appeared to be partially mediated by the opioid system. These findings could support the long-term use of A. ludoviciana for treating painful complaints in Mexican folk medicine.

Cadinane-Type Sesquiterpenoids from Heterotheca inuloides: Absolute Configuration and Anti-inflammatory Activity.

Eight cadinane-type sesquiterpenoids (1-8) together with some triterpenoids, flavonoids, and sterols were isolated from the aerial parts of Heterotheca inuloides. The structures of the new compounds (1-4) were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis. The structures of the new (1-3) and the known (5-7) sesquiterpenoids were confirmed by X-ray crystallography. The absolute configurations of metabolites 2-5 were determined by comparing their experimental and calculated electronic circular dichroism spectra and confirmed via refinement of the Flack parameter using anomalous X-ray scattering from the oxygen atoms and chemical correlation methods. The sesquiterpenoids were evaluated for their anti-inflammatory potential by applying the TPA-induced mouse ear edema model. The results revealed that some of these metabolites exhibit moderate anti-inflammatory activity. At a dose of 228 µg/ear compound 1 showed 43.14 ± 8.09% inhibition on ear edema, indicating an IC50 > 228 µg/ear.

Gastroprotective effect of diligustilide isolated from roots of Ligusticum porteri coulter & rose (Apiaceae) on ethanol-induced lesions in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Ligusticum porteri Coulter& Rose (LP) has been traditionally used by the ethnic group Raramuri in the North of México for treatment of diabetes, tuberculosis, stomachaches, diarrhea and ritual healing ceremonies. It is use as antiulcer remedy has been extended to all Mexico. AIM OF THE STUDY: To evaluate the gastroprotective activity of LP organic extracts and the major natural product diligustilide (DLG),using as experimental model the inhibition of the ethanol-induced lesions in rats. MATERIALS AND METHODS: Gastric ulcers were induced by intragastric instillation of absolute ethanol (1 mL). We tested the gastroprotective activity of the organic extracts of LP and the pure compound DLG. The ulcer index (UI) was determined to measure the activity. In order to elucidate the action mechanism of DLG the animals were treated with L-NAME, N-ethylmalemide, Forskolin, 2',5'-dideoxyadenosine, Indomethacin, Glibenclameide, Diazoxide, NaHS and DL-Propargylglycine. The pylorus-ligated rat model was used to measure gastric secretion. RESULTS: The oral administration of organic extracts of Ligusticum porteri showed gastroprotective effect at 30 mg/Kg on ethanol induced gastric lesions; hexane and dichloromethane extracts were the most active. DLG was the major compound in the hexane extract. This compound at 10 mg/kg prevented significantly the gastric injuries induced by ethanol. The alkylation of endogenous non-protein-SH groups with N-ethylmaleimide abolished the gastroprotective effect of DLG and blocking the formation of endogenous prostaglandins by the pretreatment with indomethacin attenuated the gastroprotective effect of DLG. CONCLUSION: The gastroprotective activity demonstrated in this study tends to support the ethnomedical use of Ligusticum porteri roots. DLG, isolated as major compound of this medicinal plant has a clear gastroprotective effect on the ethanol-induced gastric lesions. The results suggest that the antiulcer activity of DLG depends on the participation of the endogenous non-protein -SH groups and prostaglandins.

α-Glucosidase Inhibitors from Vauquelinia corymbosa.

The α-glucosidase inhibitory activity of an aqueous extract and compounds from the aerial parts of V. corymbosa was demonstrated with yeast and rat small intestinal α-glucosidases. The aqueous extract inhibited yeast α-glucosidase with a half maximal inhibitory concentration (IC50) of 28.6 µg/mL. Bioassay-guided fractionation of the extract led to the isolation of several compounds, including one cyanogenic glycoside [prunasin (1)], five flavonoids [(-)-epi-catechin (2), hyperoside (3), isoquercetin (4), quercitrin (5) and quercetin-3-O-(6''-benzoyl)-ß-galactoside (6)] and two simple aromatic compounds [picein (7) and methylarbutin (8)]. The most active compound was 6 with IC50 values of 30 µM in the case of yeast α-glucosidase, and 437 µM in the case of the mammalian enzyme. According to the kinetic analyses performed with rat and yeast enzymes, this compound behaved as mixed-type inhibitor; the calculated inhibition constants (Ki) were 212 and 50 µM, respectively. Molecular docking analyses with yeast and mammalian α-glucosidases revealed that compound 6 bind differently to these enzymes. Altogether, the results of this work suggest that preparations of V. corymbosa might delay glucose absorption in vivo.

Evaluation of the diuretic activity in two Mexican medicinal species: Selaginella nothohybrida and Selaginella lepidophylla and its effects with ciclooxigenases inhibitors.

ETHNOPHARMACOLOGICAL RELEVANCE: Doradilla is a plant that has a long history in the Mexican traditional system of medicine for gall and renal stones, diuresis, stomach and liver inflammation among other diseases. Major components isolated from these plants include biflavonoids as amentoflavone (1), robustaflavone (2) and (S)-2,3-dihydrorobustaflavone (3) and the carbohydrate trehalose (4). The aim of this study was to evaluate the diuretic effect of the decoction of Selaginella nothohybrida Valdespino and Selaginella lepidophylla (Hook & Grev) Spring (Selaginellaceae), and compounds 1-4. We also explored the probable mode of action comparing the effects when using nonspecific and specific COX׳s inhibitors. MATERIALS AND METHODS: Three biflavonoids (1-3) were isolated from the ethyl acetate extraction of the aqueous decoction and the carbohydrate trehalose (4) from the aqueous phase. The structures of all compounds were elucidated by spectroscopic methods and comparisons were made against published data. The diuretic activity was assessed in mice by oral administration of the decoctions in doses of 1000 and 2000mg/kg and biflavonoids 1-3 and trehalose (4) in a dose range of 10mg/kg using furosemide as a standard drug. Inhibitors of COX׳s such as acetyl salicylic acid, sodium naproxen, indomethacin and Celebrex were also assayed to analyze the involvement of renal prostaglandins in diuresis. Water excretion rate, pH, density, conductivity, and contents of Na(+) and K(+) were measured in the urine of mice. RESULTS: Decoction of Selaginella lepidophylla showed lower effect in the urine output at doses of 1000 and 2000mg/kg, while decoction of Selaginella nothohybrida produced an increase at 2000mg/kg (P<0.05). Urinary electrolytes excretion was also affected by this last extract and pure compounds: decoction diminished urinary excretion of sodium and potassium ions, so as compounds 1 and 4; compounds 2 and 3 observed just a natriuretic effect. Pretreated mice with COX׳s inhibitors and then with test compounds 1, 2, 4 and decoction showed inhibition of diuresis in all cases exception for treatment with trehalose (4); natriuretic effect was observed in all cases except for biflavonoid robustaflavone (2) which behaved as the reference compound furosemide. Selaginella nothohybrida decoction behaved similarly to COX-2 inhibitor Celebrex (8), inhibiting diuresis. CONCLUSIONS: Selaginella nothohybrida presents a moderate diuretic effect, which appears to be in partly mediated by the presence of biflavonoids and trehalose. Renal prostaglandins may be involved in the mechanism of diuresis. The present results provide a quantitative basis explaining the traditional folk medicine use of Selaginella nothohybrida as a diuretic agent by Mexican population.

Hypoglycemic, antihyperglycemic, and antioxidant effects of the edible plant Anoda cristata.

ETHNOPHARMACOLOGICAL RELEVANCE: Some studies refer that the entire plant of Anoda cristata is consumed as food and medicine; in particular for treating diabetes, inflammation, fever, cough, and wounds. The aim of this study was to establish the preclinical efficacy of Anoda cristata as hypoglycemic and/or antihyperglycemic agent using well-known animal models. MATERIALS AND METHODS: The acute toxicity was analyzed by the Lorke method. Acute hypoglycemic as well as oral glucose and sucrose tolerance tests were used to determine the hypoglycemic and antihyperglycemic action of Anoda cristata. Several preparations of the plant, including a mucilage (M), an aqueous (T-AE), a free mucilage aqueous (FM-AE), and an organic (OE) extracts, were tested in healthy and NA-STZ-hyperglycemic mice. Glibenclamide (15mg/kg), acarbose (5mg/kg ) and metformin (200mg/kg) were used as positive controls. The major compounds acacetin (1) and diosmetin (2), isolated from an infusion of the plant applying chromatographic methods, were evaluated as hypoglycemic agents using the same assays. The FM-AE was tested also in rats with metabolic syndrome induced by a high-fructose fed. Finally some assays were performed to determine the antioxidant capacity of the FM-AE in vitro. RESULTS: The results demonstrated that the extracts and compounds from Anoda cristata were effective for reducing blood glucose levels in healthy and NA-STZ-hyperglycemic mice when compared with vehicle groups (p<0.05). The FM-AE exerted also positive effect over different biochemical parameters altered in rats with metabolic syndrome induced by a fructose diet. FM-AE has also antioxidant action effectively trapping ONOO(-) and ROO(•) radicals. The major flavonoids isolated from the plant, namely acacetin (1) and diosmetin (2), caused significant hypoglycemic effect and possessed antioxidant activity. CONCLUSION: Anoda cristata is effective to diminish glucose levels in vivo and to ameliorate different disorders related with the metabolic syndrome in rats. According to the results, the efficacy of Anoda cristata preparations could be due to the presence of active principles with different mode of actions at the molecular level, including α-glycosidases inhibitors, insulin secretagogues, glucose entrapment and radical trapping agents.