Medicinal plants: Concentrators and superconcentrators of copper and its role in metabolism of these species

With the combination of the atomic absorption method and spectrophotometry, we conducted the testing of medicinal plants of Russian flora (approximately 200 species) on the content of copper (Cu). We revealed 36 species—concentrators and superconcentrators of this element. The capability of these species to accumulate Cu is compared with the synthesis of physiologically active compounds (PAC), among which alkaloids and phenolic compounds prevail. The stimulating influence of Cu on the formation and accumulation of alkaloids of main structural types—derivatives of chinolysidine, isochinoline, tropane, and indole—is established. The data about the role of Cu-containing enzymes in the metabolism of alkaloids, as well as of phenolic compounds, are reviewed on the example of flavonoids. The role of concentrated copper in the medicinal effect of medicinal plants and, thus, the appearing perspective to widen their application spectrum, especially in the cases when the orientation of the action of PAC and Cu are different, is discussed.     

Chemical Features of Medicinal Plants (Review)

Data on chemical composition related to the synthesis of physiologically active substances (alkaloids, terpenoids, glycosides, phenolic compounds, etc.) and to the accumulation of individual elements or groups of five to ten elements (e.g., Cr, Co, Mn, and Zn) in medicinal plants were reviewed. Chemical features of medicinal plants serve as an integral determinant of their species specificity and pharmacological properties and enable their wide use in medical practice. The relationship between the synthesis of physiologically active substances and accumulation of elements is mediated by several levels of molecular regulation.     

Chemistry of medicinal plants (review)]

Data on the chemical composition related to synthesis of physiologically active substances (alkaloids, terpenoids, glycosides, phenolic compounds, etc.), and accumulation of individual elements or groups of five to ten elements (e.g., Cr, Co, Mn, and Zn) in medicinal plants were reviewed. Chemical features of medicinal plants serve as an integral determinant of their species specificity and pharmacological properties and enabling their wide use in medical practice. The relationship between the synthesis of physiologically active substances and accumulation of elements is mediated by several levels of molecular regulation.     

Physiological activities and the active constituents of potentially medicinal plants used by wild chimpanzees of the Mahale mountains,Tanzania

Potential medicinal plants for wild chimpanzees have been studied in order to discover their physiologically active compounds. Tests of the physiological activity of 3 plant species—Vernonia amygdalina, Aspilia mossambicensis, andFicus exasperata—indicate that they contain a variety of active compounds. From one species,V. amygdalina, an antitumor agent and 2 possible antitumor promoters are identified. Furthermore, steroid glucosides were isolated as the bitter substances. These structurally new compounds are expected to exhibit a number of significant physiological activities. The chemical investigation of possible medicinal plants used by chimpanzees should be helpful in recovering naturally occurring compounds of medicinal significance for human use.     

Plant hormones and plant growth regulators in plant tissue culture

Summary This is a short review of the classical and new, natural and synthetic plant hormones and growth regulators (phytohormones) and highlights some of their uses in plant tissue culture. Plant hormones rarely act alone, and for most processes— at least those that are observed at the organ level—many of these regulators have interacted in order to produce the final effect. The following substances are discussed: (a) Classical plant hormones (auxins, cytokinins, gibberellins, abscisic acid, ethylene and growth regulatory substances with similar biological effects. New, naturally occurring substances in these categories are still being discovered. At the same time, novel structurally related compounds are constantly being synthesized. There are also many new but chemically unrelated compounds with similar hormone-like activity being produced. A better knowledge of the uptake, transport, metabolism, and mode of action of phytohormones and the appearance of chemicals that inhibit synthesis, transport, and action of the native plant hormones has increased our knowledge of the role of these hormones in growth and development. (b) More recently discovered natural growth substances that have phytohormonal-like regulatory roles (polyamines, oligosaccharins, salicylates, jasmonates, sterols, brassinosteroids, dehydrodiconiferyl alcohol glucosides, turgorins, systemin, unrelated natural stimulators and inhibitors), as well as myoinositol. Many of these growth active substances have not yet been examined in relation to growth and organized developmentin vitro.     

Acidithiobacillus thiooxidans secretome containing a newly described lipoprotein Licanantase enhances chalcopyrite bioleaching rate

The nature of the mineral–bacteria interphase where electron and mass transfer processes occur is a key element of the bioleaching processes of sulfide minerals. This interphase is composed of proteins, metabolites, and other compounds embedded in extracellular polymeric substances mainly consisting of sugars and lipids (Gehrke et al., Appl Environ Microbiol 64(7):2743–2747, 1998). On this respect, despite Acidithiobacilli—a ubiquitous bacterial genera in bioleaching processes (Rawlings, Microb Cell Fact 4(1):13, 2005)—has long been recognized as secreting bacteria (Jones and Starkey, J Bacteriol 82:788–789, 1961; Schaeffer and Umbreit, J Bacteriol 85:492–493, 1963), few studies have been carried out in order to clarify the nature and the role of the secreted protein component: the secretome. This work characterizes for the first time the sulfur (meta)secretome of Acidithiobacillus thiooxidans strain DSM 17318 in pure and mixed cultures with Acidithiobacillus ferrooxidans DSM 16786, identifying the major component of these secreted fractions as a single lipoprotein named here as Licanantase. Bioleaching assays with the addition of Licanantase-enriched concentrated secretome fractions show that this newly found lipoprotein as an active protein additive exerts an increasing effect on chalcopyrite bioleaching rate.     

Inhibition of mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase 2 (Cdk2) by platinum(II) phenanthroline complexes

Inhibition of protein kinases in the fight against disease remains a constant challenge for medicinal chemists, who have screened multitudes of predominantly planar organic scaffolds, natural and synthetic, to identify potent—albeit not always selective—kinase inhibitors. Herein, in an effort to investigate the potential biological utility of metal-based compounds as inhibitors against the cancer-relevant targets mitogen-activated protein kinase and cyclin-dependent kinase 2, we explore various parameters in planar platinum(II) complexes with substituted phenanthroline ligands and aliphatic diamine chelate co-ligands, to identify combinations that yield promising inhibitory activity. The individual ligands’ steric requirements as well as their pattern of hydrogen bond donors/acceptors appear to alter inhibitory potency when modulated.     

Influence of intramolecular interactions on conformational and dynamic properties of analogs of heptapeptide AFP<Subscript>14–20</Subscript>

Conformational and dynamic properties of proteins and peptides play an important role in their functioning. However, mechanisms that underlie this influence have not been fully elucidated. In the present work we computationally constructed analogs of heptapeptide AFP_14–20 (LDSYQCT) — one of the biologically active sites of human α-fetoprotein (AFP) — to study their conformational and dynamic properties using molecular dynamics simulation. Analogs were obtained by point substitutions of amino acid residues taking into account differences in their physicochemical properties and also on the basis of analysis of amino acid substitutions in the AFP_14–20-like motifs revealed in different physiologically active proteins. It is shown that changes in conformational mobility of amino acid residues of analogs are due to disruption or arising of intramolecular interactions that, in turn, determine existence of steric restrictions during rotation around covalent bonds of the peptide backbone. Substitution of an amino acid by another one with significant difference in physicochemical properties may not lead to remarkable changes in conformational and dynamic properties of the peptide if intramolecular interactions remain unchanged.     

Cannabinoids and Gliomas

Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endogenous substances—the endocannabinoids—that activate specific cell surface receptors. Cannabinoids exert various palliative effects in cancer patients. In addition, cannabinoids inhibit the growth of different types of tumor cells, including glioma cells, in laboratory animals. They do so by modulating key cell signaling pathways, mostly the endoplasmic reticulum stress response, thereby inducing antitumoral actions such as the apoptotic death of tumor cells and the inhibition of tumor angiogenesis. Of interest, cannabinoids seem to be selective antitumoral compounds, as they kill glioma cells, but not their non-transformed astroglial counterparts. On the basis of these preclinical findings, a pilot clinical study of Δ⁹-tetrahydrocannabinol (THC) in patients with recurrent glioblastoma multiforme has been recently run. The good safety profile of THC, together with its possible growth-inhibiting action on tumor cells, justifies the setting up of future trials aimed at evaluating the potential antitumoral activity of cannabinoids.     

Investigation of antioxidant activity of quinoline thioderivatives

Antioxidant activity of new synthetic physiologically active substances (thioderivatives of quinoline) are investigated using the complex of primary estimation techniques in vitro and in vivo. It is shown that the compounds investigated display both antiradical and anti-oxidative activity, most strongly delineated for the compounds with methoxygroup in the 6th position of quinoline cycle. The suppositions concerning the mechanism of their antioxidant activity are made.     

Antioxidant polyphenols from the mycelial culture of the medicinal fungi Inonotus xeranticus and Phellinus linteus

Aims:  The medicinal fungi Inonotus xeranticus and Phellinus linteus in the family Hymenochaetaceae have been used as traditional medicines for the treatment of various diseases. However, the compound responsible for the antioxidant activity is still unknown. Therefore, this study was conducted to characterize the antioxidant substances present in cultured broths made from these fungi.
Methods and Results:  Antioxidant fractions of the cultured broths obtained from I. xeranticus and P. linteus were analysed using reversed-phase HPLC, which revealed several peaks that exhibited a potent free radical scavenging activity. To identify these antioxidant peaks, an I. xeranticus strain was mass-cultured, and the cultured broth was separated using antioxidant activity-guided fractionation. Four major active substances were purified and identified as hispidin and its dimers, 3,14'-bihispidinyl, hypholomine B, and 1,1-distyrylpyrylethan based on spectroscopic analyses. All compounds exhibited a significant scavenging activity against these radical species in a concentration-dependent manner.
Conclusions:  Antioxidant substances found in the cultured broths of the medicinal fungi I. xeranticus and P. linteus were identified as hispidin and its dimers, 3,14'-bihispidinyl, hypholomine B, and 1,1-distyrylpyrylethan.
Significance and Impact of the Study:  Polyphenol antioxidants were isolated from the cultured broth of the medicinal fungi I. xeranticus and P. linteus and identified based on extensive spectroscopic analyses. These compounds exhibited a strong antioxidant activity.     

Simultaneous determination and quantification of three pentacyclic triterpenoids—betulinic acid,oleanolic acid,and ursolic acid—in cell cultures of <Emphasis Type="BoldItalic">Lantana camara</Emphasis> L.

A simple procedure has been described for simultaneous determination and improved yield of three pentacyclic triterpenoids—betulinic, oleanolic, and ursolic acids—from callus cultures of Lantana camara. Cell biomass was obtained from leaf disk explants cultured on Murashige and Skoog (Physiol Plant 15:473–497, 1962) medium supplemented with 5 μM 6-benzylaminopurine, 1 μM 2,4-dichlorophenoxyacetic acid, and 1 μM α-naphthaleneacetic acid. Optimum separation of the three compounds was achieved by reverse-phase high-pressure liquid chromatography on a C₁₈ column with 80:20 (v/v) acetonitrile/water as mobile phase. With this route, a yield of 3.1% betulinic acid, 1.88% oleanolic acid, and 4.12% ursolic acid per gram dry weight was obtained from cultures. Leaves from the parent plant, used as control, showed total absence of betulinic acid, and the quantities of oleanolic and ursolic acids present in them were only marginally higher than that found in in vitro-raised cultures. Presence of the three compounds was further confirmed by electrospray ionization mass spectrometry.     

Tibetan medicine plurality

Tibetan medicine historically has had multiple medical lineages, despite ancient, shared literary medical canons. However, since the second half of the 20th century in Tibet, increasing state control and commoditization has lead to centralization and standardization of Tibetan medicine. Here we investigate how much variation in the use of medicinal plants remains in contemporary Tibetan medicine. Medicinal plants used and/or sold by fifteen Tibetan medical institutions, markets, and doctors, as well as two additional non-Tibetan markets, are inventoried and vouchered (where allowed). The data are ordered by Non-metric Multidimensional Scaling. Four distinct groups are defined: (1) government recognized Tibetan medical institutions and their disciples both in Lhasa and elsewhere, (2) local herbal doctors near Mt. Khawa Karpo, eastern Himalayas, (3) Tibetan medicinal markets in Lhasa and near Mt. Khawa Karpo, and (4) non-Tibetan medicinal markets near Dali and Kunming, Yunnan. This clearly documents the plurality of Tibetan medical traditions—official, local, and market—while differentiating these from non-Tibetan markets.     

Phosphoramidate derivatives of acyclovir,inhibitors of herpes virus replication

A series of new acyclovir phosphoramidates—potential antiviral agents against resistant strains of herpes virus—was synthesized. Of several approaches used for their synthesis, the treatment of the intermediate phosphorochloridate with various amines proved to be optimal. Two of the synthesized compounds were moderately active against HSV-1.     

LC-NMR: a new tool to expedite the dereplication and identification of natural products

The rapid identification of known or undesirable compounds from natural products extracts — “dereplication” — is an important step in an efficiently run natural products discovery program. Dereplication strategies use analytical techniques and database searching to determine the identity of an active compound at the earliest possible stage in the discovery process. In the past few years, advances in technology have allowed the development of tandem analytical techniques such as liquid chromatography mass spectrometry (LC-MS), LC-MS-MS, liquid chromatography nuclear magnetic resonance (LC-NMR), and LC-NMR-MS. LC-NMR, despite its lower sensitivity as compared to LC-MS, provides a powerful tool for rapid identification of known compounds and identification of structure classes of novel compounds. LC-NMR is especially useful in instances where the data from LC-MS are incomplete or do not allow confident identification of the active component of a sample. LC-NMR has been used to identify the marine alkaloid aaptamine as the active component in an extract of the sponge Aaptos sp. This extract had been identified as an enzyme inhibitor by a high throughput screening (HTS) effort. Isolated aaptamine exhibited an IC₅₀=120 μM against this enzyme. Strategies for the identification of aaptamine and for the use of LC-NMR in a natural products HTS program are discussed. Journal of Industrial Microbiology & Biotechnology (2000) 25, 342–345. Received 30 March 2000/ Accepted in revised form 03 July 2000     

Two-step concerted mechanism for alkane hydroxylation on the ferryl active site of methane monooxygenase

 A two-step concerted mechanism for the conversion of methane to methanol catalyzed by soluble methane monooxygenase (sMMO) is discussed. We propose that the enzymatic reaction mechanism is essentially the same as that of the gas-phase methane-methanol conversion by the bare FeO⁺ complex. In the initial stage of our mechanism, the ferryl (Fe—O) "iron" active site of intermediate Q and substrate methane come into contact to form the initial Q (CH₄) complex with an OFe—CH₄ bond. The C—H bonds of methane are significantly weakened by the formation of a five-coordinate carbon species, through orbital interactions between a C _3v - or D _2d -distorted methane and the Fe—O active site. The important transition state for an H atom abstraction exhibits a four-centered structure. The generated intermediate involves an HO—Fe—CH₃ moiety, and it is then converted into the final product complex including methanol as a ligand through a methyl migration that occurs via a three-centered transition state. The two-step concerted mechanism is consistent with recent experiments on regioselectivity of enzyme-catalyzed alkane hydroxylations. Received: 15 September 1997 / Accepted: 20 December 1997     

The Inclusion and Selection of Medicinal Plants in Traditional Pharmacopoeias—Evidence in Support of the Diversification Hypothesis

The Inclusion and Selection of Medicinal Plants in Traditional Pharmacopoeias—Evidence in Support of the Diversification Hypothesis. An ethnobotanical study with phytochemical analyses was undertaken to examine the medicinal plants used by residents of a small rural community in northeastern Brazil. The present work tested two ideas that attempt to explain the inclusion and selection of medicinal plants in a given culture: the diversification hypothesis and the concept of versatility. The study involved 101 people and used semistructured interviews. A total of 61 plants were selected, including 25 exotic and 36 native species. Plants were classified according to their habit and analyzed for their phytochemical components. In addition, the relative importance (RI) of these plants was calculated, and a chemical diversity index (CDI) was created and applied to each of the species. Exotic and native plants were found to have significantly different occurrences of certain classes of compounds; this result supports the diversification hypothesis. It was therefore concluded that exotic plants are included in traditional pharmacopoeias to fill therapeutic vacancies that native plants cannot satisfy.     

Noscapinoids with anti-cancer activity against human acute lymphoblastic leukemia cells (CEM): a three dimensional chemical space pharmacophore modeling and electronic feature analysis

We have identified a new class of microtubule-binding compounds—noscapinoids—that alter microtubule dynamics at stoichiometric concentrations without affecting tubulin polymer mass. Noscapinoids show great promise as chemotherapeutic agents for the treatment of human cancers. To investigate the structural determinants of noscapinoids responsible for anti-cancer activity, we tested 36 structurally diverse noscapinoids in human acute lymphoblastic leukemia cells (CEM). The IC₅₀ values of these noscapinoids vary from 1.2 to 56.0 μM. Pharmacophore models of anti-cancer activity were generated that identify two hydrogen bond acceptors, two aromatic rings, two hydrophobic groups, and one positively charged group as essential structural features. Additionally, an atom-based quantitative structure–activity relationship (QSAR) model was developed that gave a statistically satisfying result (R ² = 0.912, Q ² = 0.908, Pearson R = 0.951) and effectively predicts the anti-cancer activity of training and test set compounds. The pharmacophore model presented here is well supported by electronic property analysis using density functional theory at B3LYP/3-21*G level. Molecular electrostatic potential, particularly localization of negative potential near oxygen atoms of the dimethoxy isobenzofuranone ring of active compounds, matched the hydrogen bond acceptor feature of the generated pharmacophore. Our results further reveal that all active compounds have smaller lowest unoccupied molecular orbital (LUMO) energies concentrated over the dimethoxy isobenzofuranone ring, azido group, and nitro group, which is indicative of the electron acceptor capacity of the compounds. Results obtained from this study will be useful in the efficient design and development of more active noscapinoids.     

Adaptive radiation of photosynthetic physiology in the Hawaiian lobeliads: dynamic photosynthetic responses

Hawaiian lobeliads have radiated into habitats from open alpine bogs to densely shaded rainforest interiors, and show corresponding adaptations in steady-state photosynthetic light responses and associated leaf traits. Shaded environments are not uniformly dark, however, but punctuated by sunflecks that carry most of the photosynthetically active light that strikes plants. We asked whether lobeliads have diversified in their dynamic photosynthetic light responses and how dynamic responses influence daily leaf carbon gain. We quantified gas exchange and dynamic light regimes under field conditions for ten species representing each major Hawaiian sublineage. Species in shadier habitats experienced shorter and less numerous sunflecks: average sunfleck length varied from 1.4 ± 1.7 min for Cyanea floribunda in shaded forest understories to 31.2 ± 2.1 min for Trematolobelia kauaiensis on open ridges. As expected, the rate of photosynthetic induction increased significantly toward shadier sites, with assimilation after 60 s rising from ca. 30% of fully induced rates in species from open environments to 60% in those from densely shaded habitats. Uninduced light use efficiency—actual photosynthesis versus that expected under steady-state conditions—increased from 10 to 70% across the same gradient. In silico transplants—modeling daily carbon gain using one species’ photosynthetic light response in its own and other species’ dynamic light regimes—demonstrated the potential adaptive nature of species differences: understory Cyanea pilosa in its light regimes outperformed gap-dwelling Clermontia parviflora, while Clermontia in its light regimes outperformed Cyanea. The apparent crossover in daily photosynthesis occurred at about the same photon flux density where dominance shifts from Cyanea to Clermontia in the field. Our results further support our hypothesis that the lobeliads have diversified physiologically across light environments in Hawaiian ecosystems and that those shifts appear to maximize the carbon gain of each species in its own environment. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.