Phenological and geographical influence in the concentration of selected bioactive 4-phenylcoumarins and chlorogenic acid in Hintonia latiflora leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Hintonia latiflora is a Mexican medicinal plant with well-documented ethnomedical record comprising more than 400 years; in modern Mexico is used for treating several maladies such as diabetes and gastric ulcers. Although the pharmacological actions of the stem-bark and leaves have been demonstrated, the phenological and geographical effect on the concentration of active principles remains unexplored. AIM OF THE STUDY: The main goals of this study were to analyze the amount of selected 4-phenylcoumarins and chlorogenic acid in the leaves in order to assess the best harvesting period, and consequently their pharmacological efficacy. In addition, the preclinical antidiabetic efficacy of the infusion of the leaves was corroborated using standard pharmacological tests. MATERIALS AND METHODS: The aqueous extracts from the leaves of Hintonia latiflora were prepared by infusion. For phenological and geographical comparison, leaves of Hintonia latiflora were collected in two different regions in Chihuahua and Michoacán. The material was analyzed by UPLC applying an analytical method that developed and validated for this purpose following the ICH guidelines. Investigation of the antidiabetic action was accomplished using an acute hypoglycemic test and oral glucose and sucrose tolerance tests. RESULTS: The validated analytical method was successfully applied for quantifying chlorogenic acid (1) and 4-phenylcoumarins (2-5) in the leaves of 12 different batches (1-12) during one-year period, and seven different batches for each geographical region; the concentration of the metabolites at the phenological cycle was significantly different, their concentration increased during the pre-senescence phase whereas in the leaf renovation stage the highest concentration of 2-5 was reached. The overall analysis of the active compounds concentration between the two populations investigated seems to be less important than the phenological variations. The aqueous extract of the leaves of Hintonia latiflora exerted its antidiabetic effect by different mechanisms showing comparable effect to the organic extract. CONCLUSIONS: The findings of the present investigation reveal that the best harvest season for the leaves of Hintonia latiflora is between the leaves renovation and senescence stages avoiding the flowering period. In addition, no significant differences were found among the two different geographical populations analyzed. The infusions of the leaves, rich in 4-phenylcoumarins and chlorogenic acid, showed comparable antidiabetic action than the organic extract.

Gastroprotective effect of Hintonia latiflora and Hintonia standleyana aqueous extracts and compounds.

ETHNOPHARMACOLOGICAL RELEVANCE: The stem-barks of Hintonia latiflora and Hintonia standleyana, locally known as "copalchi", are used for treating several maladies such as diabetes and gastrointestinal complaints, including gastric ulcers. Although the antidiabetic properties have been demonstrated, the gastroprotective action remains unexplored. AIM OF THE STUDY: The main goals of this study were to establish the potential acute toxicity and the gastroprotective activity of aqueous extracts and compounds from Hintonia latiflora and Hintonia standleyana in order to demonstrate their preclinical efficacy for the treatment of gastric ulcers in Mexican folk medicine. MATERIALS AND METHODS: The aqueous extracts from the stem-barks (HLSB and HSSB) and leaves (HLL and HSL) from Hintonia latiflora and Hintonia standleyana were prepared by infusion. Investigation of the acute toxicity was accomplished by the Lorke method. The gastroprotective effect was assessed by means of a conventional ethanol-induced gastric injury model in rats using carbenoxolone as positive control. 5-O-[ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranosyl]-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin (1) and chlorogenic acid (2) were also assayed. Preliminary mechanism of action of the tested compounds was analyzed using the same pharmacological models but pretreating the animals with N(G)-nitro-L-arginine methyl ester (L-NAME), N-ethylmaleimide (NEM) and indomethacin. RESULTS: Investigation of the acute toxicity revealed that infusions of the leaves and stem-barks of both Hintonia species were not toxic to mice (LD(50)>5000 mg/kg in all cases). HLSB, HSSB, HLL and HSL provoked a significant gastroprotective effect [80.5±3.35% (ED(50)=184.7 mg/kg), 80.26±3.96%, 75.1±7.26% (ED(50)=109.1 mg/kg), 76.85±3.17% (ED(50)=149.7 mg/kg) of gastroprotection respectively]. Compounds 1 and 2, present in all the extracts, were also active [68.85±8.4% (ED(50)=15 mg/kg), 74.04±4.4% (ED(50)=26 mg/kg) of gastroprotection respectively] and their mode of action involved non-protein sulfhydryl endogenous (NP-SH) compounds, since only pretreatment with NEM inhibited their gastroprotective action. CONCLUSIONS: The present investigation tends to support the ethnomedical use of HLSB, HSSB for treating gastric ulceration. Since HLL and HSL were also active, the leaves could be use alternatively, which in terms of natural resources conservation is an outstanding finding, considering that the plant populations of both Hintonia are scarce and in danger of extinction. Mainly two compounds (1 and 2) are important active principles of the plants.

Geranins C and D, additional new antiprotozoal A-type proanthocyanidins from Geranium niveum.

Two new additional A-type proanthocyanidins have been isolated from Geranium niveum. Their structures were determined by spectroscopic, chemical and chiroptical methods as epi-afzelechin-(4beta-->8,2beta-->O-->7)-gallocatechin (1) and epi-afzelechin-(4beta-->8,2beta-->O-->7)-afzelechin-(4beta-->8,2beta-->O-->7)-afzelechin (2). Proanthocyanidins 1 and 2 were given the trivial names of geranins C and D, respectively. Compound 2 showed moderate antiprotozoal activity against Entamoeba histolytica and Giardia lamblia, whereas 1 exhibited weak activity toward E. histolytica.

Biological and mechanistic activities of xanthorrizol and 4-(1',5'-dimethylhex-4'-enyl)-2-methylphenol isolated from Iostephane heterophylla.

Xanthorrizol (1) and 4-(1',5'-dimethylhex-4'-enyl)-2-methylphenol (2) were identified as the principal antimicrobial components of a CH(2)Cl(2)-MeOH (1:1) extract derived from Iostephane heterophylla. Compound 2 is a new natural product, but has been synthesized. Both compounds exhibited low level activity (MICs of 16-32 microg/mL) against methicillin-resistant staphylococci and vancomycin-resistant enterococci. They were either inactive or poorly active against Gram-negative bacteria and yeast. Mechanistic studies performed in Escherichia coli imp suggested nonspecific inhibition of DNA, RNA, and protein synthesis by both of these compounds. Compound 1 was tested in an in vivo model; it did not provide protection to mice infected with Staphylococcus aureus.

Antiinflammatory constituents from Heterotheca inuloides.

Three new compounds, cadalen-15-oic acid (1), 3,7-dihydroxy-3(4H)-isocadalen-4-one (2), and dicadalenol (3), were isolated from the aerial parts of Heterotheca inuloides (Mexican arnica), together with the known compounds 7-hydroxycadalene (4), 7-hydroxy-4alphaH-3,4-dihydrocadalene (5), 1alpha-hydroxy-1(4H)-isocadalen-4-one (6), 1alpha-hydroxy-4alphaH-1,2,3,4-tetrahydrocadalen-15-oic acid (7), 7-(3,3-dimethylallyloxy)coumarin, caryolan-1,9beta-diol, and quercetin. The structures of the new compounds were elucidated by spectroscopic methods. The antiinflammatory activities of the extracts and the isolated compounds were evaluated by determining the inhibition of TPA-induced mouse ear edema. The natural products 3, caryolan-1,9beta-diol, and quercetin were the most active substances tested and displayed dose-dependent activities.

New modified eremophilanes from the roots of Psacalium radulifolium.

The investigation of the chemical constituents from the roots of Psacalium radulifolium, a member of the matarique complex of medicinal plants, which includes several members of the Asteraceae, resulted in the isolation of four new modified eremophilanes: radulifolin A (4), epi-radulifolin A (5), radulifolin B (6), and radulifolin C (7), together with the known natural substances cacalol, cacalone, epi-cacalone, O-methyl-1,2-dehydrocacalol, adenostin A, decompostin, and neoadenostylone. Antimicrobial evaluation of the extracts and the isolated compounds indicated that cacalol was the major active compound.

Bioactive oleanolic acid saponins and other constituents from the roots of Viguiera decurrens.

The bisdesmoside oleanolic acid saponin, 3-0-(methyl-beta-D-glucuronopyranosiduronoate)-28-0-beta-D-glucopyranosyl-oleanolate along with nine known compounds (two diterpenic acids, one chromene, three triterpenes, one steroidal glycoside, and two monodesmoside oleanolic acid saponins), were obtained from Viguiera decurrens roots. The chemical structure of the bisdesmoside oleanolic saponin was determined by chemical and NMR spectral evidence. A mixture of monodesmoside saponins displayed cytotoxic activity against P388 and COLON cell lines (ED50= 2.3 and 3.6 microg/ml, respectively). Two of the known compounds showed insecticidal activity against the Mexican bean beetle larvae (Epilachna varivestis).

Day surgery for older people (70+): selection versus outcome effects.

As length of Australian hospital stays decreased, concerns were raised about benefits of shorter stays for older people. We investigated personal characteristics, perceived health outcomes (SF-36) and service use of day-only and other patients aged 70+, at one and 12 weeks after hospital discharge. Day-only patients were younger, had better self-reported health, were selected for orthopaedic, gastrointestinal and ophthalmic procedures and used similar levels of formal and informal services after discharge as people with longer stays. There was no evidence of ill effects of day surgery for older people, but improved selection and information giving procedures can improve outcomes.

New phenylethanoids from Buddleja cordata subsp. cordata.

Bioassay-guided fractionation of a crude extract of the stem bark of Buddleja cordata subsp. cordata with significant antimycobacterial activity led to the isolation of a mixture composed by ten new long-chain esters of 2[4'-hydroxyphenyl]-ethanol (1-10), along with the lichen metabolites methyl beta-orcinolcarboxylate (11) and beta-orcinolcarboxylate (12). Extensive HPLC allowed the separation of the major components of the mixture, which were characterized by spectral means as 2[4'-hydroxyphenyl]-ethyl stearate (3), 2[4'-hydroxyphenyl]-ethyl behenate (6), and 2[4'-hydroxyphenyl]-ethyl lignocerate (8). The minor esters were identified as 2[4'-hydroxyphenyl]-ethyl palmitate (1), 2[4'-hydroxyphenyl]-ethyl heptadecanoate (2), 2[4'-hydroxyphenyl]-ethyl nonadecanoate (4), 2[4'-hydroxyphenyl]-ethyl arachidate (5), 2[4'-hydroxyphenyl]-ethyl tricosanoate (7), 2[4'-hydroxyphenyl]-ethyl pentacosanoate (9), and 2[4'-hydroxyphenyl]-ethyl hexacosanoate (10) by GC-MS analysis of the methyl esters derivatives of the fatty acids obtained by alkaline hydrolysis of the mixture. Compound 8 exhibited moderate antibacterial activity against Mycobacterium tuberculosis (MIC = 64 micrograms/ml).

Phytotoxic compounds from Xanthocephalum gymnospermoides var. eradiatum.

Investigation of the aerial parts of Xanthocephalum gymnospermoides var eradiatum led to the isolation of two new labdane-type of diterpenes, namely, 8 alpha,13S-epoxylabdane-14S,15-diol (1) and methyl grindelate (2). In addition, grindelic acid (3), 7 alpha, 8 alpha-epoxygrindelic acid (4), 7 alpha-hydroxy-8(17)dehydrogrindelic acid (5), 17-hydroxygrindelic acid (6) and 4,5-epoxy-beta-caryophyllene (7) were obtained. The isolated compounds were characterized by spectral means. The absolute configuration of compound 1 was established by chemical correlation with 8 alpha,13S-epoxy-15-nor-labdan-14-oic acid methyl ester of known absolute stereochemistry and by using the advanced Mosher's ester methodology. The results of the present investigation indicated that the known compound barbatol (8) could be an enantiomer of compound 1. Compounds 1-3 and 7 caused significant inhibition of the radicle growth of seedlings of Amaranthus hypochondriacus.

Orizabins V-VIII, tetrasaccharide glycolipids from the Mexican scammony root (Ipomoea orizabensis).

An extensive investigation of the so-called jalapin resinoid obtained from roots of the Mexican scammony, Ipomoea orizabensis, using high field NMR spectroscopy led to the characterization of six glycosides, including the known scammonins I (1) and II (2) and four new tetrasaccharides of jalapinolic acid, orizabins V-VIII (3-6). All the isolates (1-6) were found to be weakly cytotoxic toward human oral epidermoid carcinoma (KB).

Postacute care for older aboriginal people: an exploratory-descriptive study.

Many Aboriginal people reside in rural and remote Australia. Aboriginal health workers were the informants in this exploratory-descriptive study, which explored issues pertaining to postacute care for older Aboriginal people. Qualitative analysis of interview data revealed several issues were viewed as being of crucial importance in the provision of effective postacute services to older Aboriginal people. These were: (i) identification of Aboriginality; (ii) perceived racism and stereotypical attitudes among hospital staff and healthcare workers; and (iii) effective discharge planning. Other issues which were believed to impact upon service use were identified as: (i) availability of services; (ii) knowledge of services and level of use; and (iii) the notion of mainstream versus Aboriginal-specific services. Findings are discussed in relation to available literature. Implications for further research are drawn from the findings of this exploratory study.

Geranins A and B, new antiprotozoal A-type proanthocyanidins from Geranium niveum.

Bioassay-guided fractionation of the antiprotozoal extract of Geranium niveum led to the isolation of two new A-type proanthocyanidins, epi-afzelechin-(4beta-->8, 2beta-->O-->7)-afzelechin (1) and epi-catechin-(4beta-->8, 2beta-->O-->7)-afzelechin (2). Compounds 1 and 2 were given the trivial names of geranins A and B, respectively. In addition, five known compounds, mahuannin B (3), reynoutrin (4), hyperin (5), methyl gallate (6), and 3-beta-caffeoyl-12-oleanen-28-oic acid (7), were obtained. The structures of the new proanthocyanidins were elucidated by spectroscopic and chemical methods as well as CD measurements. Compounds 1, 2, and 4-7 were tested against axenically grown trophozoites of Giardia lamblia and Entamoeba histolytica.

A new lanostane-type triterpenoid from Chamaesyce prostrata.

A new triterpenoid, namely, lanost-25-en-3-beta-ol, and two known flavonoids (kaempferol-3,6-dimethyl ether and kaempferol 7- O-glucoside) were isolated from the aerial parts of Chamaesyce prostrate (Euphorbiaceae). The structure of the new compound was established based on spectral evidences.

Perception of service needs by parents with intellectual disability, their significant others and their service workers.

It is well recognized in the literature that parents with intellectual disability require support and social services. There is growing interest in these services being responsive to parent-identified concerns, particularly as it has been suggested that parents' concerns may differ from those reported by service workers, family members, or friends. In the Australian study reported here, the views of parents with intellectual disability, their significant others and service workers were sought on parents' service needs on 20 items incorporating child care, social and community living, and domestic skills. There were significant differences in the perceptions of the parents, workers, and significant others on the help parents needed. Several gaps in services were also identified. From the parents' perspective, their greatest unmet needs were in the community participation area, specifically with help to explore work options, to know what community services are available and how to access these, and to meet people and make friends.

A comparative study of the analgesic and anti-inflammatory activities of pectolinarin isolated from Cirsium subcoriaceum and linarin isolated from Buddleia cordata.

The dried aqueous extract of aerial parts of Cirsium subcoriaceum (Asteraceae) and its major flavonoid glycoside, pectolinarin, have been evaluated for analgesic and anti-inflammatory effects in mice and rats, respectively. Both the extract and pectolinarin exerted significant and dose-dependent analgesic and anti-inflammatory activities. Also, the anti-inflammatory activities of an aqueous extract of Buddleia cordata and its principal glycoside linarin were evaluated. The results of pharmacological testing proved that linarin is a better anti-inflammatory agent than pectolinarin and indomethacin. On the other hand, pectolinarin exerted a better analgesic effect than linarin.

Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: a pilot study.

Glutamine (Gln) is an important nutrient substrate for lymphocytes and macrophages in vitro. This pilot study evaluated effects of Gln supplementation on circulating lymphocytes and lymphocyte subsets after allogeneic bone marrow transplantation (BMT). Adult patients received either parenteral nutrition supplemented by L-Gln (Gln-PN) or standard Gln-free PN after BMT. Leukocyte and total lymphocyte counts were determined during hospitalization, and flow cytometry studies of peripheral mononuclear cells were performed 1 to 2 weeks after hospital discharge. The Gln-PN group demonstrated a higher percentage of blood lymphocytes during hospitalization. At flow cytometry, patients who received Gln-PN had an increased total lymphocyte count (332 +/- 50 versus 590 +/- 71 cells/microL, P = 0.010); greater numbers of total T lymphocytes (54 +/- 19 versus 229 +/- 70 cells/microL, P = 0.030); and higher CD4+ and CD8+ T-lymphocyte counts in peripheral blood compared with controls. Gln-PN may support lymphocyte recovery after BMT.

Smooth muscle relaxing flavonoids and terpenoids from Conyza filaginoides.

Activity-guided fractionation of the smooth muscle relaxing, chloroform-methanol (1:1) extract of Conyza filaginoides (D.C.) Hieron (Asteraceae) led to the isolation of three flavonoids (quercetin 3-glucoside, rutin, and pinostrobin), one sterol (alpha-spinasterol), a sesquiterpenoid (beta-caryophyllene 4,5-alpha-oxide), and two triterpenoids (erythrodiol and 3-beta-tridecanoyloxy-28-hydroxyolean-12-ene). 3-beta-Tridecanoyloxy-28-hydroxy-olean-12-ene is a new naturally occurring terpenoid. All the isolated compounds induced a concentration-dependent inhibition of the spontaneous contractions of rat ileum. The spasmolytic activity exhibited by the extract and active principles tends to support the traditional use of C filaginoides as an antispasmodic agent.

Analgesic and antipyretic activities of an aqueous extract and of the flavone linarin of Buddleia cordata.

The dried aqueous extract of leaves of Buddleia cordata (loganiaceae) and its main flavonoid glycoside, linarin, have been evaluated for analgesic and antipyretic effects in mice and rats, respectively. Both the extract and linarin exerted significant and dose-dependent analgesic and antipyretic activities, the first being obtained against a chemical stimulus (writhing a test in mice) and the second being obtained by a pyretogenic stimulus (yeast-induced hyperthermia test). Furthermore, the response of the animals in the hot plate test was modified by linarin and an aqueous extract. These activities were similar to that showed by morphine sulfate (MS) and they were inhibited by naxolone pretreatment, a specific morphinic antagonist compound. These findings lead to the conclusion that the aqueous extract and linarin exert central analgesic properties. On the other hand, linarin was shown to be responsible for the antipyretic activity of this species.

Phytogrowth-inhibitory and antifungal constituents of Helianthella quinquenervis.

Investigation on the roots of Helianthella quinquenervis (Hook.) A. Gray (Asteraceae), led to the isolation of one new benzofuran (6-methoxy-tremetone (1)) and a new prenylacetophenone (4-beta-D-(glucopyranosyloxy)-3-[3-methoxy-trans-isopenten-1 -yl] acetophenone (3)). In addition, 6-hydroxy-3-methoxytremetone (2), encecalin (6), euparin (5), demethylencecalin (4), and angelic acid were obtained. Structural assignments of the isolated compounds were based on spectroscopic and spectrometric analysis. Natural products 1-4 showed marginal cytotoxicity against three human tumor cell lines [MCF-7, A-549, and HT-29]. Compounds 4 and 6 inhibited the radicle growth of Amaranthus hypochondriacus and Echinochloa crusgalli. Furthermore, substances 4-6 exhibited antifungal activity against Trichophyton mentagrophytes.