PubMed Health⌕ Search

Biomedical subjects

Michael Heinrich

Publications and source records attributed to Michael Heinrich.

At least 37 records · Page 2Linked to original sources

Historical and modern medicinal plant uses--the example of the Ch'orti' Maya and Ladinos in Eastern Guatemala.

Local empirical knowledge about medicinal properties of plants is the basis for their use as home remedies. Particularly in developing countries such remedies still are an indispensable resource for everyday health care. They form the basis for numerous studies on drugs from natural sources. Like other indigenous groups across the world, the Ch'orti' Maya in Eastern Guatemala are currently experiencing a phase of dramatic cultural change, with their traditional knowledge about plants being in great danger of disappearing. During 17 months of fieldwork, medicinal plant uses were documented using a semi-quantitative approach and analysed using ethnopharmacological methods. The most important groups of illnesses treated with plants were gastrointestinal complaints and illnesses associated with pain and fever. Field data were compared with mostly unpublished historical data collected in the 1930s by the anthropologist Charles Wisdom. This comparison showed that medicinal plant uses that are more consistent over time are also shared by a larger number of people. A literature search on the most frequently mentioned medicinal plants showed that, even for widely used medicinal species, phytochemical and pharmacological data are insufficient for fully understanding their therapeutic profile. Whereas a few examples of potentially dangerous practices were encountered, the limited amount of information available mostly supports local medicinal plant usage.

Ethnobotany↗

Calcium ionophoretic and apoptotic effects of ferutinin in the human Jurkat T-cell line.

We have investigated the ionophoretic and apoptotic properties of the daucane sesquiterpene ferutinin and three related compounds, ferutidin, 2-alpha-hydroxyferutidin and teferin, all isolated from various species of plants from the genus Ferula. Ferutinin induced a biphasic elevation of intracellular Ca2+ in the leukemia T-cell line, Jurkat. First, a rapid calcium peak was observed and inhibited by BAPTA-AM. This initial calcium mobilization was followed by a sustained elevation, mediated by the entry of extracellular calcium through L-type calcium channels and sensitive to inhibition by EGTA. Moreover, ferutinin-induced apoptosis in Jurkat cells, and this event was preceded, in a cyclosporine-A sensitive manner, by a loss of mitochondrial transmembrane potential (DeltaPsim) and by an increase in intracellular reactive oxygen species. Ferutinin-induced DNA fragmentation was mediated by a caspase-3-dependent pathway, and was initiated independently of any specific phase of the cell cycle. The evaluation of ferutinin analogs in calcium mobilization and apoptosis assays showed strict structure-activity relationships, with p-hydroxylation of the benzoyl moiety being requested for activity.

Apoptosis↗

Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation.

We previously demonstrated that the aspartate protease cathepsin D is activated by ceramide derived from acid sphingomyelinase. Increased expression of cathepsin D in the skin has been reported in wound healing, psoriasis and skin tumors. We explored specific functions of cathepsin D during epidermal differentiation. Protein expression and enzymatic activity of cathepsin D increased in differentiated keratinocytes in both stratified organotypic cultures and in mouse skin during epidermal barrier repair. Treatment of cultured keratinocytes with exogenous cathepsin D increased the activity of transglutaminase 1, known to cross-link the cornified envelope proteins involucrin and loricrin during epidermal differentiation. Inhibition of cathepsin D by pepstatin A suppressed the activity of transglutaminase 1. Cathepsin D-deficient mice revealed reduced transglutaminase 1 activity and reduced protein levels of the cornified envelope proteins involucrin and loricrin. Also, amount and distribution of cornified envelope proteins involucrin, loricrin, filaggrin, and of the keratins K1 and K5 were significantly altered in cathepsin D-deficient mice. Stratum corneum morphology in cathepsin D-deficient mice was impaired, with increased numbers of corneocyte layers and faint staining of the cornified envelope only, which is similar to the human skin disease lamellar ichthyosis. Our findings suggest a functional link between cathepsin D activation, transglutaminase 1 activity and protein expression of cornified envelope proteins during epidermal differentiation.

Animals↗

Antifungal constituents of Melicope borbonica.

Fractionation of extracts of the leaves of Melicope borbonica (syn. Euodia borbonica var. borbonica), a medicinal plant from the Réunion Island that is traditionally used for wound healing and other ailments, afforded an acetophenone (xanthoxylin) and two coumarins, scoparone and limettin, as the major constituents. All three compounds exhibited moderate antifungal activity against Candida albicans and Penicillium expansum, in accordance with the traditional use of the plant. Moreover, 2,4,6-trimethoxyacetophenone (methylxanthoxylin), three other coumarins [7-(3-methyl-2-butenyloxy)-6-methoxycoumarin, cedrelopsin and psoralen], two sesquiterpenes (alpha-curcumene and 3,6-epidioxy-1,10-bisaboladiene), eugenol, methyleugenol and a lignan (sesamin) were isolated. None of the isolated constituents exhibited antiin fl ammatory activity in vitro. No alkaloids were detected.

Antifungal Agents↗

Compartmentalization of TNF receptor 1 signaling: internalized TNF receptosomes as death signaling vesicles.

The molecular regulation of the recruitment of initial signaling complexes at the TNF-R1 is poorly defined. We demonstrate here that within minutes internalized TNF-R1 (TNF receptosomes) recruits TRADD, FADD, and caspase-8 to establish the "death-inducing signaling complex" (DISC). In addition, we identified the TNF-R1 internalization domain (TRID) required for receptor endocytosis and provide evidence that TNF-R1 internalization, DISC formation, and apoptosis are inseparable events. Analyzing cell lines expressing an internalization-deficient receptor (TNF-R1 DeltaTRID) revealed that recruitment of RIP-1 and TRAF-2 to TNF-R1 occurred at the level of the plasma membrane. In contrast, aggregation of TRADD, FADD, and caspase-8 to establish the TNF-R1-associated DISC is critically dependent on receptor endocytosis. Furthermore, fusion of TNF receptosomes with trans-Golgi vesicles results in activation of acid sphingomyelinase and cathepsin D. Thus, TNF receptosomes establish the different TNF signaling pathways by compartmentalization of plasma membrane-derived endocytic vesicles harboring the TNF-R1-associated DISC.

Adaptor Proteins, Signal Transducing↗

Galanthamine from snowdrop--the development of a modern drug against Alzheimer's disease from local Caucasian knowledge.

In recent years, galanthamine isolated from several members of the Amaryllidaceae (Leucojum spp., Narcissus species, Galanthus spp.) has become an important therapeutic options used to slow down the process of neurological degeneration in Alzheimer's disease. This review traces aspects of the history of its development from little known observational studies in the Caucasus Mountains (Southern Russia), to the use of this drug in Eastern European countries (esp. Bulgaria) in the treatment of poliomyelitis and ultimately to the recent introduction onto Western markets in the treatment of Alzheimer's disease. Of note, little is known about the early history of the drug's development and the review also points to other gaps in our knowledge about the ethnopharmacology, pharmacology and clinical use of galanthamine.

Alzheimer Disease↗

Coumarins from Opopanax chironium. New dihydrofuranocoumarins and differential induction of apoptosis by imperatorin and heraclenin.

Opopanax chironium is a rich source of furano- and dihydrofuranocoumarins, whose accumulation in all plant parts and especially the roots is presumably responsible for the poisonous properties of the species. The presence of two distinct chemotypes was evidenced, with the one from Sicily affording the new dihydrofuranocoumarins 5d and 5e, while extracts from the Sardinian chemotype showed powerful apoptotic activity, which was traced to the prenylated furanocoumarins heraclenin (2a) and imperatorin (2b). Despite a close structural similarity, compounds 2a and 2b induced apoptosis in Jurkat leukemia cells in mechanistically different ways.

Antineoplastic Agents↗

Imperatorin inhibits T-cell proliferation by targeting the transcription factor NFAT.

In our ongoing research into anti-inflammatory compounds from medicinal plants in the Mediterranean area, we have isolated several furanocoumarins from the roots of Oppopanax chironium (L.), and have evaluated them for activity related to T-cell functionality. Heraclenin (1) and imperatorin (2) significantly inhibited T cell receptor-mediated proliferation in human primary T cells in a concentration-dependent manner. In transient transfection experiments with a plasmid containing the IL-2 promoter we found that imperatorin is a potent inhibitor of IL-2 gene transcription. To further characterize the inhibitory mechanisms of imperatorin at the transcriptional level, we examined the DNA-binding and transcriptional activities of NF-kappaB, NFAT, and AP-1 transcription factors in Jurkat T cells. We found that imperatorin inhibited both the NFAT binding to DNA and transcriptional activities, without affecting significantly the activation of the NF-kappaB and AP-1 transcription factors. These findings provide new insights into the molecular mechanisms involved in the immunomodulatory and anti-inflammatory activities of natural furanocoumarins.

Anti-Inflammatory Agents, Non-Steroidal↗

Cytotoxic versus anti-inflammatory effects in HeLa, Jurkat T and human peripheral blood cells caused by guaianolide-type sesquiterpene lactones.

Four guaianolide type sesquiterpene lactones (SL), namely the new 1,2-dihydro-3-oxo-costic acid guaianyl ester 3beta-O-(1,2-didehydro-3-oxo-costoyloxy)-4beta,10beta-dihydroxy-guaia-1(2)-en-6beta,12-olide (1) and 3beta-O-(1,2-didehydro-3-oxo-costoyloxy)-4beta,10beta-dihydroxy-guaia-1(2)-en-6alpha,12-olide (2), as well as the known moroccolide A [5alphaH-2beta,4-epoxy-3beta-hydroxy-guaia-1(10),11(13)-dien-6beta,12-olide, 3] and 3beta-O-(2-methylbutyryl)-moroccolide A [5alphaH-2beta,4-epoxy-3beta-(2-methylbutyryloxy)-guaia-1(10),11(13)-dien-6beta,12-olide, 4] were examined for their cytotoxic and anti-inflammatory effects in HeLa, Jurkat T and human peripheral blood mononuclear cells. Compounds 1, 2 and 4 were found to exert a strong cytotoxicity similar in potency in all investigated cell types, whereas 3 was significantly less active. Along with the cytotoxic effect compounds 1 and 4 showed a potent and comparable down-regulation of the mRNAs of the house-keeping genes beta-actin and GAP-DH in PBMCs after 20 h. In contrast, the down-regulation of the PMA-induced mRNA levels of the NF-kappaB-driven pro-inflammatory genes IL-2, IL-6, GM-CSF, TNF-alpha, and IL-1beta in PBMCs is significantly stronger with compound 4. Compound 3 did not significantly modulate cytokine mRNAs levels at biochemically relevant concentrations. The electromobility shift assay (EMSA), revealed a stronger inhibition of NF-kappaB for 1 (IC(50) 2.5 microM) than for 4 (IC(50) 5 microM). Both compounds were also subjected to an IL-6 luciferase reporter gene assay and showed IC(50) values of 1.0 (1) and 1.2 microM (4). Thus, the NF-kappaB inhibition measured by EMSA, as well as the IL-6 luciferase assay did not reflect the differential modulation of pro-inflammatory genes measured with RT-rt-PCR.

Animals↗

Activity of Zanthoxylum clava-herculis extracts against multi-drug resistant methicillin-resistant Staphylococcus aureus (mdr-MRSA).

In a continuing search for compounds with antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA) possessing multidrug ef flux systems, we have demonstrated activity associated with extracts from Southern prickly ash bark, Zanthoxylum clava-herculis. Bioassay-guided isolation of an alkaloid extract led to the characterization of the benzo[c]phenanthridine alkaloid chelerythrine as the major active principle. This compound exhibited potent activity against strains of MRSA, which were highly resistant to clinically useful antibiotics via multidrug ef flux mechanisms.

Anti-Bacterial Agents↗

Antiquity of medicinal plant usage in two Macro-Mayan ethnic groups (México).

In the biological sciences the use of medicinal plants in indigenous cultures is commonly seen as being based on a long tradition ('traditional medicine'). However, under normal circumstances, ethnobotanical studies cannot provide evidence on the antiquity of specific uses for medicinal plants since oral traditions have a limited historical depth and archaeological evidence does not provide evidence for the specific medicinal use of a certain plant. Here, we provide evidence for the antiquity of medicinal plant use in the Olmec region in Mexico by comparing the pharmacopoeias of the linguistically related Lowland Mixe and Zoque-Popoluca. These cultures, separated for about 2000 years, have cognates for vernacular medicinal plant names in common. For fifteen species such cognate names were detected. Also, a statistically significant segment of the medicinal flora is used for similar purposes. Overall, 123 species are shared between the two groups and of these 62 have a similar usage. In nine cases they also have a similar name. These findings make a transmission of such knowledge since the time of the Olmecs highly likely.

History, 20th Century↗

Biflavonoids with cytotoxic and antibacterial activity from Ochna macrocalyx.

Six biflavonoid and related compounds were isolated from the ethanolic extract of Ochna macrocalyx bark. One is a new compound, the isoflavanone dimer dehydroxyhexaspermone C ( 1). Previously isolated compounds obtained from the bark are biisoflavonoid hexaspermone C ( 2). tetrahydrofuran derivative ochnone ( 3). furobenzopyran derivative cordigol ( 4). and biflavonoids calodenin B ( 5). and dihydrocalodenin B ( 6). Although 3 has already been isolated, its spectral data are presented here for the first time. Isolated compounds were tested for cytotoxic activity on MCF-7 breast cancer cells using the MTT reduction assay method. Compound 5 showed cytotoxic activity (7 +/- 0.5 microM) and 6 showed moderate cytotoxicity (35 +/- 7 microM). In antibacterial assays performed using three strains of multi-drug resistant (mdr) Staphylococcus aureus (RN4220, XU212 and SA-1199-B) compounds 5 and in particular 6 showed strong antibacterial activity (MICs 5 : 64, 8, 16 microg/mL 6 : 8, 8, 8 microg/mL, respectively). The ethanolic extract of the bark also showed NF-kappaB inhibitory activity.

Anti-Bacterial Agents↗

Ethnobotany and natural products: the search for new molecules, new treatments of old diseases or a better understanding of indigenous cultures?

Results of various projects on Mexican Indian ethnobotany and some of the subsequent pharmacological and phytochemical studies are summarised focusing both on chemical-pharmacological as well as anthropological (ethnopharmacological) aspects of our research. We have identified taste and smell properties of medicinal (vs. non-medicinal) plants as important indigenous selection criteria. There exist well-defined criteria specific for each culture, which lead to the selection of a plant as a medicine. This field research has also formed a basis for studies on bioactive natural products from selected species. The bark of Guazuma ulmifolia showed antisecretory activity (cholera toxin-induced chloride secretion in rabbit distal colon in an USSING chamber). Active constituents are procyanidins with a polymerisation degree of eight or higher. Byrsonima crassifolia yielded proanthocyanidins with (+) epicatechin units and Baccharis conferta showed a dose-dependent antispasmodic effect with the effect being particularly strong in flavonoid-rich fractions. Our ethnopharmacological research led to the identification of sesquiterpene lactones (SLs) like parthenolide as potent and relatively specific inhibitors of the transcription factor NF-kappaB, an important mediator of the inflammatory process. The inhibitory effect of SLs is very strongly enhanced by the presence of such groups as the isoprenoid ring system, a lactone ring containing a conjugated exomethylene group (alpha-methylene-gamma-lactone) and an alpha,beta-unsaturated cyclopentenone or a conjugated ester moieties. Our work also elucidated the NF-kappaB inhibiting activity of the photosensitiser phaeophorbide A from Solanum diflorum (Solanaceae) in PMA induced HeLa cells. Hyptis verticillata yielded a series of lignans as well as sideritoflavone, rosmarinic acid and (R)-5-hydroxypyrrolidin-2-one and is rich in essential oil (rich in alpha-pinene, beta-pinene and thymol). Other species investigated include Begonia heracleifolia, Crossopetalum gaumerii, Epaltes mexicana, Pluchea symphytifolia and Xanthosoma robustum.

Biological Products↗

Inhibition of LPS-induced p42/44 MAP kinase activation and iNOS/NO synthesis by parthenolide in rat primary microglial cells.

Nitric oxide (NO) has been implicated in the etiopathology of central nervous system (CNS) diseases such as multiple sclerosis (MS). Inhibition of NO synthesis has been proposed to be a possible mechanism of action of relevance in the treatment of multiple sclerosis and migraine. Here, we investigated the effect of parthenolide on inducible NO synthase (iNOS) synthesis and NO release using primary rat microglia. We found parthenolide to be an inhibitor of iNOS/NO synthesis. Investigating the molecular mechanisms by which parthenolide prevents iNOS/NO synthesis, we found that parthenolide inhibits the activation of p42/44 mitogen-activated protein kinase (MAPK), but not IkBalpha (IkappaBalpha) degradation or nuclear factor-kappaB (NF-kappaB) p65 activation. The data suggest that parthenolide might have a potential in the treatment of CNS diseases where NO is part of the pathophysiology.

Animals↗

Ethnopharmacy of the ethnic Albanians (Arbëreshë) of northern Basilicata, Italy.

Intercultural studies about the methods of use and perceptions of traditional remedies in Europe are strategically important in understanding how pharmaceutical means in our multicultural modern societies are differently accepted by diverse ethnic groups. In this survey, we analysed the biological means traditionally used in the ethnomedicine of three Arbëreshë (ethnic Albanians) communities in the Vulture area (northern Lucania, southern Italy). The majority of remedies are represented by plants belonging to 54 botanical taxa. A few of the recorded species have a traditional therapeutic use that has never previously been reported in southern Italy. Other means-especially used in the past-are comprised of mineral, animal and industrial derived materials. In specific cases, some of these materials and even plants are neither applied externally or internally, but are instead utilised as symbolic ritual objects in spiritual healing ceremonies. Ethnopharmacological and anthropological considerations about these usages are discussed.

Albania↗

Yucatec Mayan medicinal plants: evaluation based on indigenous uses.

As part of an ethnopharmacological field study 48 medicinal plants were evaluated using several biological assays with the goal to obtain information on the pharmacological effects of these plants, which may be of direct relevance to the indigenous uses. Three species used to treat gastrointestinal disorders showed remarkable activity against Helicobacter pylori. One of them showed activity against Giardia duodenalis. Cytotoxic effects against KB cells were found for six species. In the group of plants used for dermatological conditions several species were active against gram-positive bacteria and Candida albicans. Two plant species of this group were found to be active in an Nuclear Factor-kappaB (NF-kappaB) assay measuring inhibition of this pro-inflammatory transcription factor. A species of the Solanaceae, applied in cases of pain and fever, showed a weak activity against Plasmodium falciparum. One species traditionally used for diabetes exhibited antihyperglycemic activity. None of the six species from the group of 'women's medicine' showed relevant affinity to the D(2) dopamine receptor. Based on this evaluation, plants with strong activities should be further investigated phytochemically and pharmacologically to identify active fractions and compounds.

Animals↗

Ethnopharmacology of liakra: traditional weedy vegetables of the Arbëreshë of the Vulture area in southern Italy.

An ethnobiological field study on food plants and medicinal foods traditionally consumed in three Arbëresh (ethnic Albanian) communities in northern Lucania (southern Italy) document approximately 120 botanical taxa used for these purposes. Non-domesticated food vegetables (liakra), mostly gathered during the spring season, play a central role as traditional functional food. Quantitative ethnobotanical, ethnotaxonomical, ethnoecological, ethnogastronomical, and ethnopharmacological aspects related to gathering, processing, cooking and consumption of liakra are discussed. Unusual food species, such as Lycium europeaum, Centaurea calcitrapa, and a few spontaneous weedy Asteraceae and Brassicaceae species are locally used in the kitchen. Most of these are very poorly known phytochemically and phytopharmacologically. Moreover, an analysis of taste perception of the most commonly used botanical foods was conducted in the village of Ginestra. Arbëresh taste classification and indigenous criteria related to the perception of bitter taste in considering non-cultivated plants as food or medicine are discussed as well.

Cooking↗

Medicinal plants of the Popoluca, México: organoleptic properties as indigenous selection criteria.

The taste and smell of the environment are important to humans in everyday life and are of particular relevance for the selection of medicinal versus non-medicinal plant species. In a 16-months study with the Popoluca of southern Veracruz (Mexico), we focused on the indigenous selection criteria for medicinal plants. We provide evidence for a highly significant association between organoleptic properties of plants and the use of these species as medicine. Additionally, the doctrine of signature is an essential mnemonic aid, which facilitates remembering the use assigned to the plant. From the Popoluca point of view, it is essential to find substitutes or alternative treatments when a certain species is not at hand. We show that organoleptic properties and the doctrine of signature are excellent guides for selecting or memorising such medicinals.

Color↗