Search

Metabolic syndrome describes the human condition characterized by the presence of coexisting traditional risk factors for cardiovascular disease, such as hypertension, dyslipidemia, glucose intolerance, and obesity, in addition to nontraditional cardiovascular disease risk factors, such as inflammatory processes and abnormalities of the blood coagulation system. Although the specific etiology for metabolic syndrome is not known, insulin resistance--a clinical state in which a normal or elevated insulin concentration reflects an impaired biological response--is present and is considered a key pathophysiologic abnormality. As such, metabolic syndrome can be considered to be a prediabetic state and contributes greatly to increased morbidity and mortality in humans. Given the public health significance of metabolic syndrome, successful strategies are direly needed to intervene in its development. As such, nutritional supplementation with botanicals that effectively address pathogenic mechanisms, combined with the acceptance and widespread use of botanical supplements by the general public, represents an attractive, novel, and potentially effective approach to the problem. Thus, the overall goal of our botanical research center is to comprehensively evaluate botanicals in addressing the pathophysiologic mechanisms that lead to the development of insulin resistance and metabolic syndrome. Currently, each of the 3 research projects evaluates a specific botanical [Russian tarragon (Artemisia dracunculus L), shilianhua (Sinocrassula indica), and grape (Virus vinifera) anthocyanins] and assesses the effect on pathogenic mechanisms leading to the development of insulin resistance. With the completion of our research, we anticipate a better understanding of the cellular mechanisms by which insulin resistance develops and the role of botanicals in modulating the progression to metabolic syndrome. KEY WORDS Artemisia dracunculus L, shilianhua, anthocyanins, insulin, insulin resistance, botanicals

Many similarities exist between research on combinatorial chemistry and natural products and research on dietary supplements and botanicals at the National Institutes of Health (NIH) Botanical Research Centers. The technologies used at the centers are similar to those used by other NIH-sponsored investigators. All centers rigorously examine the authenticity of botanical dietary supplements and determine the composition and concentrations of the phytochemicals therein, most often by liquid chromatography-mass spectrometry. Several of the centers specialize in fractionation and high-throughput evaluation to identify the individual bioactive agent or a combination of agents. Some centers are using DNA microarray analyses to determine the effects of botanicals on gene transcription with the goal of uncovering the important biochemical pathways they regulate. Other centers focus on bioavailability and uptake, distribution, metabolism, and excretion of the phytochemicals as for all xenobiotics. Because phytochemicals are often complex molecules, synthesis of isotopically labeled forms is carried out by plant cells in culture, followed by careful fractionation. These labeled phytochemicals allow the use of accelerator mass spectrometry to trace the tissue distribution of [sup.14]C-labeled proanthocyanidins in animal models of disease. State-of-the-art proteomics and mass spectrometry are also used to identify proteins in selected tissues whose expression and posttranslational modification are influenced by botanicals and dietary supplements. In summary, the skills needed to carry out botanical centers' research are extensive and may exceed those practiced by most NIH investigators. KEY WORDS Activity-guided fractionation, bioavailability, isotopic labeling of phytochemicals in plant cell culture, DNA microarray analysis, 2D-gel electrophoresis, peptide mass fingerprinting, tandem mass spectrometry

Botanical preparations have been used medicinally for thousands of years. Many commercially available botanical products are being marketed in the United States with little or no publicly available scientific validation of efficacy or consistency. For botanicals to be reliable for research purposes and consumer products, they must be standardized with sufficient quality controls to ensure consistent composition, safety, and potency. This includes uniform cultivation of source plants with controls to monitor for contamination from other species, pesticides, and environmental toxins. The active components of botanicals must be identified by activity-guided fractionation with the use of in vitro assays that require little test material followed by validation in vivo. Concentrations of active compounds within the botanicals can then be accurately measured to ensure the delivery of a dependable dose in the final product. The use of bioenhancing agents may be considered for compounds with poor bioavailability. Standardization of botanical therapeutics can only be achieved when the active compounds are identified and biological activity is confirmed, thus ensuring a consistent product. KEY WORDS Botanicals, standardization, bioactivity, bioassay-guided fractionation, LC-MS analysis, bioenhancers

Two new diprenylated coumaric acid isomers (1aand 1b) and two known congeners, capillartemisin A (2) and B (3), were isolated from Artemisia scopariaas bioactive markers using bioactivity-guided HPLC fractionation. Their structures were determined by spectroscopic means, including 1D and 2D NMR methods and LC-MS, with their purity assessed by 1D 1H pure shift qNMR spectroscopic analysis. The bioactivity of compounds was evaluated by enhanced accumulation of lipids, as measured using Oil Red O staining, and by increased expression of several adipocyte marker genes, including adiponectin in 3T3-L1 adipocytes relative to untreated negative controls. Compared to the plant’s 80% EtOH extract, these purified compounds showed significant but still weaker inhibition of TNFα-induced lipolysis in 3T3-L1 adipocytes. This suggests that additional bioactive substances are responsible for the multiple metabolically favorable effects on adipocytes observed with Artemisia scopariaextract.

Herbal tea kinkéliba prepared from the leaves of Combretum micranthumhas been widely consumed in West African countries for its flavor, nutritional and medicinal properties. Under bio-guided screening, the kinkéliba leaves were chemically investigated using various chromatographic and spectrometric methods that led to the identification of thirteen different flavonoid compounds. Further biological tests illustrated that the identified compounds may have synergistic effects to decrease the expression of phosphoenolpyruvate carboxykinase (PEPCK) mRNA and glucose production in an H4IIE hepatoma cell line, indicating its potential use for insulin-resistant diabetes treatment. Further in vivostudy on C57BL/6J mice indicates that kinkéliba can lower plasma glucose levels in a dose-dependent manner without significant weight loss and toxicity. The ethyl acetate extract in rich of flavonoids could also increase the glucose tolerance (GT) after seven weeks' administrations. Both in vitroand in vivoexperiments support a potential new application of kinkéliba leaves as an anti-diabetes agent.

Complementing classical drug discovery, phytochemicals act on multiple pharmacological targets, especially in botanical extracts, where they form complex bioactive mixtures. The reductionist approach used in bioactivity-guided fractionation to identify single bioactive phytochemicals is inadequate for capturing the full therapeutic potential of the (bio)chemical interactions present in such complex mixtures. This study used a DESIGNER (Deplete and Enrich Select Ingredients to Generate Normalized Extract Resources) approach to selectively remove the known bioactives, 4′-O-methyldavidigenin (1; 4,2′-dihydroxy-4′-methoxydihydrochalcone, syn. DMC-1) and its isomer 4-O-methyldavidigenin (2; syn. DMC-2), from the mixture of phytochemicals in an ethanol extract from Artemisia dracunculusto determine to what degree the more abundant 2accounts for the established antidiabetic effect of the A. dracunculusextract. Using an otherwise chemically intact “knock-out extract” depleted in 2and its regioisomer, 1, in vitro and in vivo outcomes confirmed that 2(and likely 1) acts as major bioactive(s) that enhance(s) insulin signaling in skeletal muscle, but also revealed that 2does not account for the breadth of detectable biological activity of the extract. This is the first report of generating, at a sufficiently large preparative scale, a “knock-out extract” used as a pharmacological tool for in vitro and in vivo studies to dissect the biological impact of a designated bioactive in a complex phytochemical mixture.

This paper describes the development of a stable moringa plant concentrate comprising the extraction and identiication of stable actives, via plant metabolites, and the correlation of activity through a variety of in vitro models. The resulting concentrate demonstrated direct and indirect antioxidant beneits and inhibitory action against inlammation and UV-induced MMP-1. [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicines (TCM) are rapidly gaining attention in the West as sources of new drugs, dietary supplements and functional foods. However, lack of consistent manufacturing practices and quality standards, fear of adulteration, and perceived deficiencies in scientific validation of efficacy and safety impede worldwide acceptance of TCM. In addition, Western pharmaceutical industries and regulatory agencies are partial toward single ingredient drugs based on synthetic molecules, and skeptical of natural product mixtures. This review concentrates on three examples of TCM-derived pharmaceuticals and functional foods that have, despite these usual obstacles, risen to wide acceptance in the West based on their remarkable performance in recent scientific investigations. They are: Sweet wormwood (Artemisia annua), the source of artemisinin, which is the currently preferred single compound anti-malarial drug widely used in combination therapies and recently approved by US FDA; Thunder god vine (Tripterygium wilfordii) which is being developed as a botanical drug for rheumatoid arthritis; and green tea (Camellia sinensis) which is used as a functional beverage and a component of dietary supplements.

Amplification promoting sequence (aps), from tobacco rDNA, was found to induce amplification and enhances the expression of heterologous genes, consequently increasing the expression of transgenic proteins in tobacco. In this report we demonstrate that apselement also affects integration, transcription, and translation of a soybean protease inhibitor, Bowman–Birk inhibitor (BBI), in transgenic tomato plants and quantifies its effects in different expression vectors. A synthetic bbigene was constructed, based on the wild-type gene containing two independent inhibition sites; trypsin and chymotrypsin. Transformation vectors were designed using two different promoters; the tomato fruit specific E8 promoter and the constitutively active 35S CaMV promoter. These vectors were transformed into ‘Moneymaker’ tomato plants. In tomato fruits and leaves, apscaused a 3-fold increase in bbimRNA levels when compared to the lines without aps. Similar increases were obtained in plants expressing bbicontrolled by E8 or 35S CaMV promoters. Also, the level of BBI protein expression in aps-transformed plants was 3 fold-higher than in plants without aps. This is the first report of apseffect on the enhanced gene expression and transgenic protein production in plant other than tobacco.Amplification promoting sequence (aps), from tobacco rDNA, was found to induce amplification and enhances the expression of heterologous genes, consequently increasing the expression of transgenic proteins in tobacco. In this report we demonstrate that apselement also affects integration, transcription, and translation of a soybean protease inhibitor, Bowman–Birk inhibitor (BBI), in transgenic tomato plants and quantifies its effects in different expression vectors. A synthetic bbigene was constructed, based on the wild-type gene containing two independent inhibition sites; trypsin and chymotrypsin. Transformation vectors were designed using two different promoters; the tomato fruit specific E8 promoter and the constitutively active 35S CaMV promoter. These vectors were transformed into ‘Moneymaker’ tomato plants. In tomato fruits and leaves, apscaused a 3-fold increase in bbimRNA levels when compared to the lines without aps. Similar increases were obtained in plants expressing bbicontrolled by E8 or 35S CaMV promoters. Also, the level of BBI protein expression in aps-transformed plants was 3 fold-higher than in plants without aps. This is the first report of apseffect on the enhanced gene expression and transgenic protein production in plant other than tobacco.

Winter cress (Barbarea verna) seed preparations rich in phenethylisothiocyanate (PEITC) had strong in vivo and in vitro anti-inflammatory activity, significantly reducing the size of carrageenan-induced rat paw edema. This in vivo effect was comparable with that of the nonsteroidal anti-inflammatory drug aspirin. The seed preparation, in a concentration-dependent manner, reduced the mRNA levels of inflammation-related genes such as the inducible forms of cyclooxygenase and nitric-oxide synthase and the proinflammatory cytokine interleukin in lipopolysaccharide-stimulated mouse macrophage cell line RAW 264.7. Activity of the seed preparation was similar to that of the synthetic PEITC. PEITC was the most active of five different forms of isothiocyanate tested for their effects on in vitro proinflammatory gene expression. In vitro activity of the seed preparation was also compared with that of two known anti-inflammatory drugs. We conclude that Barbarea verna seed preparation may function as a potent anti-inflammatory agent, interfering with the transcription of proinflammatory genes.

The modern pharmaceutical industry based on synthetic chemistry severed the historical connection between plants, food and medicines. The growing costs of discovering new chemical entity-based drugs through high throughput screening methods may yet again reconnect plants and human health at a new level of technological sophistication. Multicomponent botanical therapeutics that comprise functional foods, dietary supplements and botanical drugs hold several advantages over conventional drugs that may earn them a more prominent place in the medicine of the future. They can deliver mixtures of multi-functional molecules with potentiating and synergistic effects and pleiotropic targeting at a reasonable cost and with fewer regulatory constraints. They are well suited for long-term disease prevention in an era of genetic testing and increased life expectancy. They also provide additional vehicles for delivering health and wellness. Technologies that address the needs of discovery, development and manufacturing of multi-component botanical therapeutics are emerging. They include computational and bioinformatics approaches, cell based gene expression and high-content screening systems, and phytochemical elicitation and unique plant cultivation / extraction methods designed to optimize the production of bioactives, standardize overall extract composition and assure batch-to-batch product consistency. Nevertheless, multi-component botanical therapeutics carry risks associated with potential interactions with conventional drugs and adverse reactions, which are difficult to detect and diagnose. They face problems of acceptance by the medical community and pharmaceutical industry, safety and efficacy validation, poor standardization and quality control, and difficulties in identifying active ingredients and determining their complex mode(s) of action. Solving these problems will accelerate the merger of grocery stores with pharmacies and agriculture with chemical manufacturing and provide physicians and patients with broader and more individualized choices for disease prevention and treatment.

The effects of soil pH, different levels of nitrogen (N), phosphoras (P), and potassium (K), alone and in combination on cadmium (Cd) uptake by Indian mustard [Brassica juncea (L.) Czen., cv '426308'] were studied under greenhouse conditions. Results showed that Cd concentration in aboveground biomass at soil pH 5.5 was three times more than at pH 6.5 and 7.5. Treatments without N application at pH 5.5 had the highest Cd concentrations in the aboveground biomass. Dry weight of aboveground biomass was significantly lower atpH 5.5 compared to pH 6.5 and 7.5. Total Cd uptake at pH 6.5 increased by 2 to 2.5 times compared to uptake at soil pH 5.5. Those conditions for maximum Cd accumulation by the aboveground biomass of Indian mustard from Cd-contaminated soil occurs at soil pH 6.5 and when the application rates of N, P, and K are at 200, 100, and 66 kg ha-1, respectively.

By accumulating Cd from solution, roots of hydroponically grown Indian mustard (Brassica juncea L.), a high biomass crop plant, were able to cause substantial reductions in the concentration of Cd in solution. The removal of Cd from solution was linearly correlated with Cd accumulation by roots. Screening of 300 different rhizobacterial isolates identified several that, when inoculated onto roots of Indian mustard, significantly enhanced the total amount of Cd removed from solution. Further investigations revealed that this enhancement was because of an overall increase in root biomass in the rhizobacterial-treated plants. Rhizobacteria were found to accumulate Cd from solution, and ultrastructural observations suggested that rhizobacteria promote the precipitation of Cd on the root surface. By precipitating Cd at the root surface, rhizobacteria reduce the amount of Cd taken up into roots, thereby protecting the plants, and in particular the roots, from the toxic effects of Cd. This reduced Cd toxicity allows for the increased proliferation of roots observed when plants are inoculated with certain rhizobacteria.

In tobacco (Nicotiana tabacum L. cv. Xanthinc), salicylic acid (SA) levels increase in leaves inoculated by necrotizing pathogens and in healthy leaves located above the inoculated site. Systemic SA increase may trigger disease resistance and synthesis of pathogenesis-related proteins (PR proteins). Here we report that ultraviolet (UV)-C light or ozone induced biochemical responses similar to those induced by necrotizing pathogens. Exposure of leaves to UV-C light or ozone resulted in a transient ninefold increase in SA compared to controls. In addition, in UV-light-irradiated plants, SA increased nearly fourfold to 0.77 µg·g-1 fresh weight in leaves that were shielded from UV light. Increased SA levels were accompanied by accumulation of an SA conjugate and by an increase in the activity of benzoic acid 2-hydroxylase which catalyzes SA biosynthesis. In irradiated and in unirradiated leaves of plants treated with UV light, as well as in plants fumigated with ozone, PR proteins 1a and 1b accumulated. This was paralleled by the appearance of induced resistance to a subsequent challenge with tobacco mosaic virus. The results suggest that UV light, ozone fumigation and tobacco mosaic virus can activate a common signal-transduction pathway that leads to SA and PR-protein accumulation and increased disease resistance.

Toxic metal pollution of waters and soils is a major environmental problem, and most conventional remediation approaches do not provide acceptable solutions. The use of specially selected and engineered metal-accumulating plants for environmental clean-up is an emerging technology called phytoremediation. Three subsets of this technology are applicable to toxic metal remediation: (1) Phytoextraction—the use of metal-accumulating plants to remove toxic metals from soil; (2) Rhizoflltration—the use of plant roots to remove toxic metals from polluted waters; and (3) Phytostabilization—the use of plants to eliminate the bioavailability of toxic metals hi soils. Biological mechanisms of toxic metal uptake, translocation and resistance as well as strategies for improving phytoremediation are also discussed.

Submergence in water greatly stimulates internodal elongation in excised stem sections of deep-water rice (Oryza sativa L. cv. “Habiganj Aman II”) and inhibits growth of leaf blades and leaf sheaths. The highest rates of internodal growth have been observed in continuous light. Very little growth occurs in submerged sections kept in darkness or incubated under N2 in the light. The effect of submergence on the growth of deep-water rice is, at least in part, mediated by C2H4, which accumulates in the air spaces of submerged sections. This accumulation results from increased C2H4 synthesis in the internodes of submerged sections and reduced diffusion of C2H4 from the tissue into the water. Increased C2H4 levels accelerate internodal elongation and inhibit the growth of leaves. Compounds capable of changing the rate of C2H4 synthesis, namely aminoethoxyvinylglycine, an inhibitor of C2H4 synthesis, and 1-aminocyclopropane-1-carboxylic acid, the immediate, precursor of C2H4, have opposite effects on growth of internodes and leaves. The enhancement of internodal elongation by C2H4 is particularly pronounced in an atmosphere of high CO2 and low O2. The increase in C2H4 synthesis in internodes of submerged sections is primarily triggered by reduced atmospheric concentrations of O2. The rate of C2H4 evolution by internodes isolated from stem sections and incubated in an atmosphere of low O2 is up to four times greater than that of isolated internodes incubated in air. In contrast, C2H4 evolution from the leaves is reduced under hypoxic conditions. The effect of submergence on growth of stem sections of deep-water rice can be mimicked by exposing non-submerged sections to a gas mixture which is similar to the gaseous atmosphere in the internodal lacunae of submerged sections, namely 3% O2, 6% CO2, 91% N2 (by vol.) and 1 µl l-1 C2H4. Our results indicate that growth responses obtained with isolated rice stem sections are similar to those of intact deep-water rice plants.

Floral thermogenicity, which is found in several representatives of half a dozen angiosperm families, is most pronounced in the Araceae. It is based on the operation of an “alternative”, cyanide-resistant electron transport chain which, in contrast to the “classic” cytochrome oxidase system, produces little ATP; most of the energy originally locked up in the respiratory substrate usually starch — is therefore liberated in the form of heat. The biological function of this (biochemically wasteful) system is to release the heat to serve as a “volatilizer” for the floral odors (often containing aliphatic amines, indole and skatole) that attract the insect pollinators. This makes the survival value of thermogenesis (for the plant species) immediately clear. Thermogenicity is under tight biological control, as demonstrated by the fact that the same ceiling temperature is always reached, regardless of ambient temperature. In Eastern skunk cabbage (Symplocarpus foetidus), which flowers very early in spring, that ceiling is about 20° C, in tropical forms such as Xanthosoma robustum and Philodendron selloum, it lies in the 42°–44° C range. In several instances, e.g., in Arum and in Sauromatum, the voodoo lily, thermogenicity manifests itself as a flare-up of only a few hours' duration, a “respiratory explosion” that can lead to rates of metabolism that compare favorably with those of a hovering hummingbird. The metabolic peak is always reached at a particular time of day, which is different for the different arum lily species, and thus reduces competition for pollinators. The odors that accompany the heat are also very characteristic, appealing to different pollinator classes and further reducing such competition. In the voodoo lily and in Arum, the primary site for the production of both heat and odor is the naked appendix of the inflorescence, which acts as a specialized “osmophore” or odor carrier. The first explosion may be followed by another one several hours later, which manifests itself in the floral chamber of the inflorescence and is under strict photoperiodic control. In Sauromatum, the first metabolic explosion is triggered by a plant hormone, originally referred to as “calorigen,” which originates in the primordia of the staminate flowers and moves from there into the appendix where it exerts its action after a lag-time of about a day — an indication that synthesis of new enzymatic protein (through unblocking of certain genes?) may well be involved. In 1987, calorigen was shown to be identical with salicylic acid. This compound was already known to induce flowering in certain duck-weeds, Lemnaceae, which until recently were regarded as belonging to the same family as arum lilies. In certain water lilies (Nymphaeaceae), thermogenicity is combined with a pollination syndrome very similar to that of Arum and Sauromatum but involving temporary trap flowers.

We have recently purified calorigen, the natural trigger for heat production in the inflorescences of Sauromatum guttatumSchott (voodoo lily), a thermogenic plant, and identified it as salicylic acid. Since then an analytical assay was developed that allows the quantitation of salicylic acid in plant tissues. This assay was used to demonstrate that on the day preceding the day of blooming the levels of salicylic acid in the thermogenic organs (appendix and lower spadix) of the voodoo lily increased almost 100-fold, reaching a level of 1 μg/g of fresh weight. The level of salicylic acid in the appendix started to rise in the afternoon and reached its maximum in the late evening, whereas the maximum accumulation of salicylic acid in the lower spadix occurred late at night. The increase in salicylic acid level in the appendix was followed the next morning by a spectacular metabolic burst that lasted for about 7 hr and at its peak increased the appendix temperature by over 12°C. The second, 14-hr-long, thermogenic episode in the lower spadix started late at night and ended on the following morning, after maximum temperature increases of more than 10°C. The concentration of salicylic acid in both thermogenic tissues promptly returned to basal, preblooming levels at the end of the thermogenic periods. The thermogenic response was under strong photoperiodic and developmental control, with salicylic acid eliciting much stronger thermogenic responses in light than in darkness. Similar surges in salicylic acid occurred in nonthermogenic male and female flowers, while the concentration of salicylic acid in the spathe remained consistently below 20 ng/g of fresh weight. Of 33 analogs of salicylic acid tested, only 2,6-dihydroxybenzoic acid and acetylsalicylic acid (aspirin) were thermogenic. The activity of 2,6-dihydroxybenzoic acid exceeded that of salicylic acid.

Etiolated rice seedlings (Oryza sativaL.) exhibited marked morphological differences when grown in sealed containers or in containers through which air was passed continuously. Enhancement of coleoptile and mesocotyl growth and inhibition of leaf and root growth in the sealed containers (“enclosure syndrome”) were accompanied by accumulation of CO2and C2H4in and depletion of O2from the atmosphere. Ethylene (1 μl 1−1), high levels of CO2, and reduced levels of O2contributed equally to the increase in coleoptile and mesocotyl growth. The effect of enclosure could be mimicked by passing a gas mixture of 3% O2, 82% N2, 15% CO2(all v/v), and 1 μl l−1) C2H4through the vials containing the etiolated seedlings. The effects of high CO2and low O2concentrations were not mediated through increased C2H4production. The enclosure syndrome was also observed in rice seedlings grown under water either in darkness or in light. The length of the rice coleoptile was positively correlated with the depth of planting in water-saturated vermiculite. The length of coleoptiles of wheat, barley, and oats was not affected by the depth of planting. In rice, the length of coleoptile was determined by the levels of O2, CO2, and ethylene, rather than by light. This regulatory mechanism allows rice seedlings to grow out of shallow water in which the concentration of O2is limiting.

The article offers insights on potential solutions for natural products using plant proteins which are found mostly in foods. It asserts that formulators were made to create more eco-friendly and natural products for the personal care industry. It explores the concept of searching for an alternative to extraction methods and discusses the use of the protein approach to solvent-free extraction.

In our ongoing investigation of new compounds with activity against malaria parasites, we tested the in vitroantiplasmodial activity of fractions and purified compounds from Cassia fistulaL., a plant traditionally used by native populations of Tanzania, Zimbabwe, Mozambique and Brazil to treat malaria or symptoms associated with this disease. Crude extracts from leaves, bark and fruits were tested for their antiplasmodial activity against the chloroquine-sensitive strain of Plasmodium falciparum(D10), where leaf extracts showed the highest activity. The chloroform extract of the leaves was further bioassay-guided fractionated using a combination of centrifugal partition chromatography and flash column chromatography. Three main antiplasmodial principles, phytol (1) (IC5018.9 ± 0.60 μM), lutein (2) (IC5012.5 ± 0.35 μM), and di-lineolylgalactopyranosyl-glycerol (DLGG) (IC505.8 ± 0.27 μM) (3), were isolated and identified using spectroscopic methods. When the three active principles were tested for their cytotoxicity using a Chinese Hamster Ovarian (CHO) cell line, compound 3showed very weak toxicity (IC5075.9 ± 0.28 μM), while the other two compounds were nontoxic, even at the highest concentration tested. The study provides evidence to support the use of Cassia fistulaas an antimalarial remedy and describes the antiplasmodial constituents from the leaves.

The hexane extract from the leaves of Canella winteranaexhibited strong activity against the chloroquine sensitive (CQS) strain of Plasmodium falciparum(D10) in vitro(IC502.53 μg/mL). Bioassay guided fractionation of this extract has led to the isolation of 5 drimane-type sesquiterpenoids: 9-epideoxymuzigadial, 9-deoxymuzigadial, muzigadial, 3-β-acetoxypolygodial and the newly isolated hemiacetal, named muzigodiol, with IC50-values of 1.01, 2.19, 0.31, 2.77 and 7.43 μg/mL, respectively. The first four compounds were tested for their cytotoxicity using Chinese Hamster Ovarian (CHO) cells, where they showed IC50-values of 1.82, 33.69, 1.18, and 58.31 μg/mL, respectively. A structure-activity relationship is discussed.

The phytochemical constituents of a biologically active, standardized, 80% ethanol extract of Rhodiola heterodontawere characterized. The extract was fractionated over a Sephadex LH-20 column to afford two main fractions representing two classes of secondary metabolites: phenylethanoids and proanthocyanidins. This fractionation facilitated the identification and quantification of individual compounds in the fractions and sub-fractions using HPLC, and LC-MS. The major compounds in the phenylethanoid fraction were heterodontoside, tyrosol methyl ether, salidroside, viridoside, mongrhoside, tyrosol, and the cyanogenic glucoside rhodiocyanoside A. These seven compounds comprised 17.4% of the EtOH extract. Proanthocyanidins ranged from oligomers to polymers based on epigallocatechin and gallate units. The main identified oligomeric compounds in the proanthocyanidin fraction were epigallocatechin gallate, epigallocatechin-epigallocatechin-3-O-gallate and 3-O-galloyl-epigallocatechin-epigallocatechin-3-O-gallate, which constituted 1.75% of the ethanol extract. Tyrosol methyl ether, mongrhoside, and the two proanthocyanidin dimers were reported for the first time from this species in this study. Intra-peritoneal injection of the 80% ethanol extract increased survival time of mice under hypoxia by 192%, as an indication of adaptogenic activity.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

A chicory root extract rich in sesquiterpene lactones significantly reduced inflammation in two animal models. In a rat paw edema model, chicory extract at 50 and 100 mg/kg significantly reduced inflammation by 58 and 76%, respectively, 24 h after carrageenan injection. In a mouse collagen induced arthritis model, chicory extract (200 mg/kg) reduced paw edema by 71% while the extract was being administered, and 31% 48 h after extract administration was discontinued. Two possible modes of action were investigated, pro-inflammatory gene expression and nitric oxide production by LPS-elicited macrophages. Chicory root extract down-regulated COX-2, TNF-α, IL1β, and iNOS expression and reduced nitric oxide production in a dose dependant manner. Several compounds were isolated from the chicory extract and tested in vitroto confirm activity. Dihydrolactucopicrin and 8-deoxylactucin showed particularly high nitric oxide inhibitory activity (IC50= 13 μM for both). Dihydrolactucopicrin also was shown to down-regulate pro-inflammatory gene expression. These data demonstrate that chicory extracts rich in sesquiterpene lactones have potent anti-inflammatory activity with potential therapeutic use.

For Abstract see ChemInform Abstract in Full Text.