Showing papers in "Planta Medica in 2016"

Rosmarinic Acid--Pharmaceutical and Clinical Aspects.

Abstract: The biosynthesis and biotechnological production of Rosmarinic acid, a phenolic ester that is widespread in the plant kingdom, has been widely investigated. This compound has shown many remarkable biological and pharmacological activities, which have led to its pharmaceutical and analytical development, as well as clinical studies, which are summarized and analyzed here for the first time. This review compiles data from the Pubmed, Scopus, Scifinder, Web Of Science, and Science Direct databases published between 1990 and 2015, restricting the search to works with the keywords “Rosmarinic acid” in the title. The initial search identified more than 800 articles; after an initial screening and removal of duplicate works, the search was further refined, resulting in approximately 300 articles that were scrutinized and comprise this review. The articles were organized to describe extraction and isolation, analytical methods, pharmaceutical development, and biological and pharmacological activities [divided into nonclinical (in vitro, in vivo) and clinical studies], pharmacokinetic studies, and stability studies.

DNA Barcoding for the Identification of Botanicals in Herbal Medicine and Dietary Supplements: Strengths and Limitations.

Abstract: In the past decades, the use of traditional medicine has increased globally, leading to a booming herbal medicine and dietary supplement industry. The increased popularity of herbal products has led to a rise in demand for botanical raw materials. Accurate identification of medicinal herbs is a legal requirement in most countries and prerequisite for delivering a quality product that meets consumer expectations. Traditional identification methods include botanical taxonomy, macroscopic and microscopic examination, and chemical methods. Advances in the identification of biological species using DNA-based techniques have led to the development of a DNA marker-based platform for authentication of plant materials. DNA barcoding, in particular, has been proposed as a means to identify herbal ingredients and to detect adulteration. However, general barcoding techniques using universal primers have been shown to provide mixed results with regard to data accuracy. Further technological advances such as mini-barcodes, digital polymerase chain reaction, and next generation sequencing provide additional tools for the authentication of herbs, and may be successful in identifying processed ingredients used in finished herbal products. This review gives an overview on the strengths and limitations of DNA barcoding techniques for botanical ingredient identification. Based on the available information, we do not recommend the use of universal primers for DNA barcoding of processed plant material as a sole means of species identification, but suggest an approach combining DNA-based methods using genus- or species-specific primers, chemical analysis, and microscopic and macroscopic methods for the successful authentication of botanical ingredients used in the herbal dietary supplement industry.

Drugs and Drug Candidates from Marine Sources: An Assessment of the Current "State of Play"

Abstract: The potential of the marine environment to produce candidate compounds (structures) as leads to, or even direct drugs from, has been actively discussed for the last 50 or so years. Over this time frame, several compounds have led to drugs, usually in the area of cancer (due to funding sources). This review is designed to show where there have been successes, but also to show that in a number of disease areas, there are structures originally isolated from marine invertebrates and free-living microbes that have potential, but will need to be "adopted" by pharmaceutical houses in order to maximize their potential.

Combined LC/UV/MS and NMR Strategies for the Dereplication of Marine Natural Products

Abstract: Drug discovery from marine natural products has experienced a revival since the beginning of this century. To be successful in this field, rapid dereplication (identification of already known bioactive compounds) is essential in order to assess the chemical novelty of crude extracts and their fractions. Access to the appropriate state-of-the-art analytical instrumentation and to suitable databases is a fundamental requirement in such a task. A brief survey of the most robust LC/UV/MS- and NMR-based approaches employed for marine natural product dereplication is presented alongside a description of the procedures followed to achieve this goal in our research group.

Anticarcinogenic Effects of α-Mangostin: A Review.

Abstract: Cancer chemoprevention is a promising strategy taken to block, reverse, or retard carcinogenesis. α-Mangostin, a natural xanthone isolated from the pericarps of mangosteen, represents one of the most studied chemopreventive agents. This compound has been reported to interfere with all the major stages of carcinogenesis: initiation, promotion, and progression. A number of mechanisms have been proposed for its anticarcinogenic activities. This review summarizes the current knowledge on the mechanisms that contribute to the observed activity of α-mangostin related to (i) modulation of carcinogenic biotransformation and mitigation of oxidative damage, (ii) induction of growth arrest and apoptosis, (iii) suppression of angiogenesis and metastasis, and (iv) combination with clinical chemotherapy drugs enhancing their efficacy and decreasing the toxic side effects. In addition, pharmacokinetic and toxicological studies of α-mangostin have also been highlighted in this review. Despite an overwhelming amount of knowledge in preclinical studies, there was almost no translation of α-mangostin into the clinic. It is hoped that continuous extensive and profound research will lead to the application of α-mangostin from experimental studies to evidence-based, clinically applicable pharmacotherapy.

Chemical Adulterants in Herbal Medicinal Products: A Review

Abstract: Many herbal medicinal products have been found to contain synthetic prescription drugs as chemical adulterants. This has become evident by the number of toxicity cases and adverse reactions reported in which casualties were reported via analytical techniques that detected the presence of chemical adulterants in them, which could be responsible for their toxicity. The adulteration of herbal medicinal products with synthetic drugs continues to be a serious problem for regulatory agencies. This review provides up to date information on cases of toxicity, major chemical adulterants in herbal medicinal products, and current analytical techniques used for their detection.

Biocatalytic Synthesis of Flavonoid Esters by Lipases and Their Biological Benefits

Abstract: Several studies have described important biological activities of flavonoids such as coronary heart disease prevention, hepatoprotective, anti-inflammatory and anticancer activities, enzyme inhibition activity, and antibacterial, antifungal, and antiviral activities. Flavonoids show promising activity as natural plant-based antioxidants due to their antioxidant and free radical scavenging properties. However, their primary applications as antioxidants in the pharmaceutical, cosmetic, and food industries are limited because of their moderately hydrophilic nature. Enzymatic acylation of natural polyphenols with fatty acids or other acyl donors has been suggested for improving the lipophilic nature of the glycosylated flavonoids. This approach increases flavonoid solubility and stability in lipophilic systems. Acylation of flavonoids with different acyl donors may also introduce beneficial properties to the molecule, such as penetration through the cell membrane and improved antioxidant, antimicrobial, anti-inflammatory, antiproliferative, cytogenetic, and enzyme inhibition activities. Chemical methods for the synthesis of flavonoid esters lead to the formation of side products and the simultaneous decomposition of the flavonoids due to harsh reaction conditions. In contrast, biocatalytic acylation of flavonoids by lipases offers advantages associated to the wide availability of these enzymes, their low cost, chemo-, regio-, and enantioselectivity, mild condition processing and non-requirement of cofactors. This article is focused on the recent development of lipase-catalyzed synthesis of flavonoid esters and the impact of the acylation reaction on their biological activities.

Narciclasine - an Amaryllidaceae Alkaloid with Potent Antitumor and Anti-Inflammatory Properties.

Abstract: The isocarbostyril alkaloid narciclasine, also known as lycoricidinol, was discovered in Narcissus species (Amaryllidaceae) in 1967. A few years later, the 60S subunit of ribosomes, and thus protein biosynthesis, were shown to be directly targeted by narciclasine. Due to its selective and highly potent cytotoxic action on cancer cells, narciclasine was intensively investigated as an antitumor compound both in vitro and in vivo. However, narciclasine did not show a strong pharmacological activity in animal tumor models. During the last decade, new fascinating actions, mechanisms, and targets of narciclasine have emerged. This review intends to present a brief but comprehensive overview of these novel insights. Beneficial therapeutical actions have been reported particularly in brain tumor models. The translation elongation factor eEF1A, which does not only participate in protein biosynthesis but also in the regulation of the actin cytoskeleton, was discovered as new direct target. Moreover, narciclasine was found to trigger actin stress fiber formation via the activation of the small GTPase RhoA. Progress has also been made regarding the pharmacokinetic characterization of the alkaloid. The synthesis of a great number of narciclasine derivatives led to a substantial understanding of its pharmacophore and of the structure-activity relationships. However, an optimized compound did not result from these efforts. Most importantly, a new field of indication has emerged: Narciclasine was proven to exert profound anti-inflammatory actions in vivo. Taken together, there has been a strong advance in the preclinical knowledge about the alkaloid. Nevertheless, narciclasine has not been tested in human clinical trials up to now.

Assessment of the Authenticity of Herbal Dietary Supplements: Comparison of Chemical and DNA Barcoding Methods

Abstract: About 7 % of the U. S. population reports using botanical dietary supplements. Increased use of such supplements has led to discussions related to their authenticity and quality. Reports of adulteration with substandard materials or pharmaceuticals are of concern because such substitutions, whether inadvertent or deliberate, may reduce the efficacy of specific botanicals or lead to adverse events. Methods for verifying the identity of botanicals include macroscopic and microscopic examinations, chemical analysis, and DNA-based methods including DNA barcoding. Macroscopic and microscopic examinations may fail when a supplement consists of botanicals that have been processed beyond the ability to provide morphological characterizations. Chemical analysis of specific marker compounds encounters problems when these compounds are not distinct to a given species or when purified reference standards are not available. Recent investigations describing DNA barcoding analysis of botanical dietary supplements have raised concerns about the authenticity of the supplements themselves as well as the appropriateness of using DNA barcoding techniques with finished botanical products. We collected 112 market samples of frequently consumed botanical dietary supplements of ginkgo, soy, valerian, yohimbe, and St. Johnʼs wort and analyzed each for specific chemical markers (i.e., flavonol glycosides, total isoflavones, total valerenic acids, yohimbine, and hypericins, respectively). We used traditional DNA barcoding techniques targeting the nuclear ITS2 gene and the chloroplast gene psbA-trnH on the same samples to determine the presence of DNA of the labelled ingredient. We compared the results obtained by both methods to assess the contribution of each in determining the identity of the samples.

Bryophyllum pinnatum and Related Species Used in Anthroposophic Medicine: Constituents, Pharmacological Activities, and Clinical Efficacy

Abstract: Bryophyllum pinnatum (syn. Kalanchoe pinnata) is a succulent perennial plant native to Madagascar that was introduced in anthroposophic medicine in the early 20th century. In recent years, we conducted a large collaborative project to provide reliable data on the chemical composition, pharmacological properties, and clinical efficacy of Bryophyllum. Here, we comprehensively review the phytochemistry, as well as the pharmacological and clinical data. As to the pharmacology, special emphasis is given to properties related to the use in anthroposophic medicine as a treatment for "hyperactivity diseases", such as preterm labor, restlessness, and sleep disorders. Studies suggesting that B. pinnatum may become a new treatment option for overactive bladder syndrome are also reviewed. Tolerability is addressed, and toxicological data are discussed in conjunction with the presence of potentially toxic bufadienolides in Bryophyllum species. The few data available on two related species with medicinal uses, Bryophyllum daigremontianum and Bryophyllum delagoense, have also been included. Taken together, current data support the use of B. pinnatum for the mentioned indications, but further studies are needed to fully understand the modes of action, and to identify the pharmacologically active constituents.

Thymoquinone from Nigella sativa Seeds Promotes the Antitumor Activity of Noncytotoxic Doses of Topotecan in Human Colorectal Cancer Cells in Vitro.

Abstract: Topotecan, a topoisomerase I inhibitor, is an anticancer drug widely used in the therapy of lung, ovarian, colorectal, and breast adenocarcinoma. Due to the primary dose-limiting toxicity of topotecan, which is myelosuppressive, it is necessary to identify other chemotherapeutic agents that can work synergistically with topotecan to increase its efficacy and limit its toxicity. Many studies have shown synergism upon the combination of topotecan with other chemotherapeutic agents such as gemcitabine. Other studies have demonstrated that pre-exposing cells to naturally occurring compounds such as thymoquinone, followed by gemcitabine or oxaliplatin, resulted in higher growth inhibition compared to treatment with gemcitabine or oxaliplatin alone. Our aim was to elucidate the underlying mechanism of action of topotecan in the survival and apoptotic pathways in human colon cancer cell lines in comparison to thymoquinone, to study the proapoptotic and antiproliferative effects of thymoquinone on the effectiveness of the chemotherapeutic agent topotecan, and to investigate the potential synergistic effect of thymoquinone with topotecan. Cells were incubated with different topotecan and thymoquinone concentrations for 24 and 48 hours in order to determine the IC50 for each drug. Combined therapy was then tested with ± 2 values for the IC50 of each drug. The reduction in proliferation was significantly dose- and time-dependent. After determining the best combination (40 µM thymoquinone and 0.6 µM topotecan), cell proteins were extracted after treatment, and the expression levels of B-cell lymphoma 2 and of its associated X protein, proteins p53 and p21, and caspase-9, caspase-3, and caspase-8 were studied by Western blot. In addition, cell cycle analysis and annexin/propidium iodide staining were performed. Both drugs induced apoptosis through a p53-independent mechanism, whereas the expression of p21 was only seen in thymoquinone treatment. Cell cycle arrest in the S phase was detected with each compound separately, while combined treatment only increased the production of fragmented DNA. Both compounds induced apoptosis through the extrinsic pathway after 24 hours; however, after 48 hours, the intrinsic pathway was activated by topotecan treatment only. In conclusion, thymoquinone increased the effectiveness of the chemotherapeutic reagent topotecan by inhibiting proliferation and lowering toxicity through p53- and Bax/Bcl2-independent mechanisms.

Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Cisplatin-Induced Neuropathy in Mice

Abstract: Sativex, a cannabinoid extract with a 1 : 1 ratio of tetrahydocannabinol and cannabidiol, has been shown to alleviate neuropathic pain associated with chemotherapy. This research examined whether tetrahydocannabinol or cannabidiol alone could attenuate or prevent cisplatin-induced tactile allodynia. In experiment 1, mice (C57BL/6) received eight administrations of 2.3 mg/kg cisplatin or saline solution IP every other day to induce tactile allodynia. Mice were then administered vehicle, 100 mg/kg gabapentin, 2 mg/kg tetrahydocannabinol, or 2 mg/kg cannabidiol IP and tested 60 min later on an electronic Von Frey. In experiment 2, prevention studies, cannabidiol (0.0, 0.5, 1.0, and 2.0 mg/kg) or tetrahydocannabinol (0.0, 0.5, 1.0, and 2.0 mg/kg) was given IP 30 min prior to cisplatin administration (2.3 or 1.0 mg/kg) utilizing a six-dose alternate day protocol. In both studies, tactile responses to the hind paws were quantified in g of force using an electronic Von Frey prior to and after the cisplatin administration protocol. Cisplatin produced a reduction in g of force indicative of neuropathy that was attenuated by gabapentin, tetrahydocannabinol, and cannabidiol but not prevented by either cannabinoid. These data demonstrate that each of the major constituents of Sativex alone can achieve analgesic effects against cisplatin neuropathy.

Secondary Metabolites from Endophytic Fungus Penicillium pinophilum Induce ROS-Mediated Apoptosis through Mitochondrial Pathway in Pancreatic Cancer Cells.

Abstract: The endophytic fungus strain MRCJ-326, isolated from Allium schoenoprasum, which is also known as Snow Mountain Garlic or Kashmiri garlic, was identified as Penicillium pinophilum on the basis of morphological characteristics and internal transcribed spacer region nucleotide sequence analysis. The endophytic fungus extract was subjected to 2D-SEPBOX bioactivity-guided fractionation and purification. The anthraquinone class of the bioactive secondary metabolites were isolated and characterized as oxyskyrin (1), skyrin (2), dicatenarin (3), and 1,6,8-trihydroxy-3-hydroxy methylanthraquinone (4) by spectral analysis. Dicatenarin and skyrin showed marked growth inhibition against the NCI60/ATCC panel of human cancer cell lines with least IC50 values of 12 µg/mL and 27 µg/mL, respectively, against the human pancreatic cancer (MIA PaCa-2) cell line. The phenolic hydroxyl group in anthraquinones plays a crucial role in the oxidative process and bioactivity. Mechanistically, these compounds, i.e., dicatenarin and skyrin, significantly induce apoptosis and transmit the apoptotic signal via intracellular reactive oxygen species generation, thereby inducing a change in the mitochondrial transmembrane potential and induction of the mitochondrial-mediated apoptotic pathway. Our data indicated that dicatenarin and skyrin induce reactive oxygen species-mediated mitochondrial permeability transition and resulted in an increased induction of caspase-3 apoptotic proteins in human pancreatic cancer (MIA PaCa-2) cells. Dicatenarin showed a more pronounced cytotoxic/proapopotic effect than skyrin due to the presence of an additional phenolic hydroxyl group at C-4, which increases oxidative reactive oxygen species generation. This is the first report from P. pinophilum secreating these cytotoxic/proapoptotic secondary metabolites.

MicroRNAs as New Bioactive Components in Medicinal Plants.

Abstract: Herbal medicine has been used to treat diseases for centuries; however, the biological active components and the mechanistic understanding of actions of plant-derived drugs are permanently discussed. MicroRNAs are a class of small, non-coding RNAs that play crucial roles as regulators of gene expression. In recent years, an increasing number of reports showed that microRNAs not only execute biological functions within their original system, they can also be transmited from one species to another, inducing a posttranscriptional repression of protein synthesis in the recipient. This cross-kingdom regulation of microRNAs provides thrilling clues that small RNAs from medicinal plants might act as new bioactive components, interacting with the mammalian system.In this article, we provide an overview of the cross-kingdom communication of plant-derived microRNAs. We summarize the microRNAs identified in medicinal plants, their potential targets in mammals, and discuss several recent studies concerning the therapeutic applications of plant-based microRNAs. Health regulations of herbal microRNAs in mammals are a new concept. Continuing efforts in this area will broaden our understanding of biological actions of herbal remedies, and will open the way for the development of new approaches to prevent or treat human diseases.

Hypolipidemic Effects of Alkaloids from Rhizoma Coptidis in Diet-Induced Hyperlipidemic Hamsters.

Abstract: This study was conducted to evaluate the antihyperlipidemic activity of five major alkaloids in Rhizoma Coptidis using high-fat- and high-cholesterol-induced hyperlipidemic hamsters. Hyperlipidemic hamsters were treated with coptisine, berberine, jatrorrhizine, palmatine, epiberberine, and total Rhizoma Coptidis alkaloids with a dose of 46.7 mg/kg × day for 140 days. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids were examined after alkaloid treatment. The results showed that all therapy agents prevented body weight gain, reduced the serum total cholesterol, and increased the high-density lipoprotein cholesterol of hamsters. Berberine, jatrorrhizine, and total Rhizoma Coptidis alkaloids decreased the triglyceride level in hyperlipidemic hamsters, while coptisine, jatrorrhizine, palmatine, and total Rhizoma Coptidis alkaloids significantly suppressed the elevation of the low-density lipoprotein cholesterol level. The fecal excretion of bile acids was significantly elevated by berberine, coptisine, jatrorrhizine, palmatine, total Rhizoma Coptidis alkaloids, and orlistat. Notably, total Rhizoma Coptidis alkaloids possess a much stronger lipid-lowering effect than the pure Rhizoma Coptidis alkaloids. Quantitative reverse transcription-polymerase chain reaction analyses revealed that Rhizoma Coptidis alkaloids could retard the synthesis of cholesterol by downregulating the mRNA expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and accelerate the clearance of lipids by upregulating the low-density lipoprotein receptor, cholesterol 7α-hydroxylase, and uncoupling protein-2 expression. These findings highlight the critical role of Rhizoma Coptidis alkaloids in hyperlipidemia treatment. Thus, they need to be considered in future therapeutic approaches.

Antiviral and Cytotoxic Isocoumarin Derivatives from an Endophytic Fungus Aspergillus oryzae.

Abstract: Oryzaeins A-D (1-4), four new isocoumarin derivatives, along with five known ones (5-9) were isolated from solid cultures of an endophytic fungus Aspergillus oryzae. Their structures were elucidated by detailed spectroscopic analysis and by comparison with reported data of related derivatives. Among them, compounds 1 and 2 represent the first examples of isocoumarins possessing an unusual 2-oxopropyl group and a rare 3-hydroxypropyl group. Compounds 1 and 2 displayed moderate anti-tobacco mosaic virus activities with inhibition rates of 28.4% and 30.6%, respectively, at the concentration of 20 µM. The new compounds showed moderate inhibitory activities against several human tumor cell lines with IC50 values in the range of 2.8-8.8 µM. Supporting information available online at http://www.thieme-connect.de/products.

Naturally Occurring Diterpenoid Dimers: Source, Biosynthesis, Chemistry and Bioactivities.

Abstract: Diterpenoid dimers are rare in nature and mainly found in higher plants including the families Acanthaceae, Annonaceae, Asteraceae, Calceolariaceae, Chrysobalanaceae, Cupressaceae, Euphorbiaceae, Fabaceae, Lamiaceae, Liliaceae, Meliaceae, Rhizophoraceae, Taxaceae, Velloziaceae, and Zingiberaceae. In addition, a few diterpenoid dimers have been also reported from fungi (Psathyrellaceae), liverworts (Scapaniaceae), and a gorgonian (Gorgoniidae). They feature a wide variety of structures due to different core skeletons, linkage patterns, substituents, and configurations. Accordingly, diterpenoid dimers exhibit a broad range of bioactivities, including cytotoxic, anti-inflammatory, antimicrobial, antimalarial, and antifouling properties, which have attracted more and more research interests in the past decades. This review with 176 metabolites from 109 references provides a comprehensive and up-to-date overview of the source, biosynthesis, structure, synthesis, and bioactivities of diterpenoid dimers.

Sesquiterpene Coumarins from Ferula sinkiangensis Act as Neuroinflammation Inhibitors.

Abstract: Neuroinflammation mediated by microglia cells plays a critical role in the development of Alzheimer′s disease. To identify novel natural neuroinflammation inhibitors, a bioactivity-guided phytochemical research was performed on the traditional Chinese medicine “Awei”, that exhibited a significant inhibitory effect on nitric oxide production in over-activated microglia cells. The research identified sixteen bioactive sesquiterpene coumarins (two new and fourteen known ones) in the effective extract of Ferula sinkiangensis. Further, the anti-neuroinflammatory activities in BV-2 microglial cells were evaluated by monitoring LPS-induced nitric oxide production. In conclusion, the major constituent, (3′S, 5′S, 8′R, 9′S, 10′R)-kellerin (1.5 %, w/w), should be responsible for the anti-neuroinflammatory effect exhibited by Awei. Furthermore, it might be a potential natural therapeutic agent for Alzheimer′s disease. The research indicated moreover, that its primary mechanism is the inhibition of mRNA expression of the inflammatory cytokines nitric oxide, tumor necrosis factor-α, cyclooxygenase-2, interleukin-6 and interleukin-1β.

Topically Used Herbal Products for the Treatment of Psoriasis - Mechanism of Action, Drug Delivery, Clinical Studies.

Abstract: Psoriasis is a chronic inflammatory skin disease characterized histologically by hyperproliferation and aberrant differentiation of epidermal keratinocytes. A wide range of conventional medical therapies to treat psoriasis is established, from topical therapies and systemic medications through to phototherapy or combinations of those. However, most of these therapies have a limited efficacy and may cause a number of side effects, including cutaneous atrophy, organ toxicity, carcinogenicity, and broadband immunosuppression, which are restricting their long-term use. Therefore, it would be desirable to use herbal products as an alternative treatment for psoriasis that causes fewer side effects. For this purpose, several electronic databases and literature references were used to summarize the current knowledge acquired on the basis of animal studies and clinical trials regarding herbal products used to treat psoriasis topically. This review discusses the mechanisms of herbal products activities through (1) inhibition of the keratinocyte hyperproliferation and inducing apoptosis, (2) inhibition of immune-inflammatory reaction, (3) suppression of phosphorylase kinase (PhK) activity, and (4) inhibition of the hedgehog (Hh) signaling pathway. Moreover, the penetration of herbal products through the psoriatic skin barrier, novel herbal drug delivery systems in psoriasis treatment, and possible adverse effects of herbal therapy are discussed.

Saponin Interactions with Model Membrane Systems - Langmuir Monolayer Studies, Hemolysis and Formation of ISCOMs.

Abstract: Saponins are used in medicine due to their pharmacological and immunological effects. To better understand interactions of saponins with model membranes and natural membranes of, for example, erythrocytes, Langmuir film balance experiments are well established. For most saponins, a strong interaction with cholesterol was demonstrated in dependence of both the aglycone part and the sugar moieties and is suggested to be correlated with a strong hemolytic activity, high toxicity, and high surface activity, as was demonstrated for the steroid saponin digitonin. In general, changes in the sugar chain or in substituents of the aglycone result in a modification of the saponin properties. A promising saponin with regard to fairly low hemolytic activity and high adjuvant effect is α-tomatine, which still shows a high affinity for cholesterol. An interaction with cholesterol and lipids has also been proven for the Quillaja saponin from the bark of Quillaja saponaria Molina. This triterpene saponin was approved in marketed vaccines as an adjuvant due to the formation of immunostimulating complexes. Immunostimulating complexes consist of a Quillaja saponin, cholesterol, phospholipids, and a corresponding antigen. Recently, another saponin from Quillaja brasiliensis was successfully tested in immunostimulating complexes, too. Based on the results of interaction studies, the formation of drug delivery systems such as immunostimulating complexes or similar self-assembled colloids is postulated for a variety of saponins.

Secondary Metabolites from the Marine Algal-Derived Endophytic Fungi: Chemical Diversity and Biological Activity.

Abstract: Marine algal-derived endophytic fungi have attracted considerable attention in the most recent two decades due to their prolific production of structurally diverse secondary metabolites with various biological activities This review summarizes a total of 182 natural products isolated from marine algal-derived endophytic fungi in the past two decades The emphasis is on the unique chemical diversity of these metabolic products, together with relevant biological activities

An Ocean of Discovery: Biodiversity Beyond the Census of Marine Life

Abstract: The 70 % of Earthʼs surface covered by oceans supports significant biological diversity and immense untapped potential for marine bioproducts. The recently completed international Census of Marine Life (2000–2010) invested heavily in evaluating the diversity, abundance, and distribution of life in the ocean but concluded that at least 50 % and potentially > 90 % of marine species remain undescribed by science. Despite this potential, and numerous successes spanning pharmaceuticals, nutraceuticals, anti-foulants and adhesives, biofuels, biocatalysts (enzymes), and cosmetics, several impediments have slowed marine bioproduct development. First, the sheer size of the ocean constrains comprehensive exploration. Second, marine taxonomists and ecologists generally do not focus on the most promising groups for bioproduct development. Third, the geographic mismatch between (often remote) biodiversity hotspots and science capacity limit discovery. Despite these challenges, new ocean sampling tools (digital imaging, remote vehicles, genetic approaches, in situ samplers), many developed or improved during the Census of Marine Life, should enhance future marine biodiversity and thus marine bioproduct discovery.

Monitoring Metabolite Profiles of Cannabis sativa L. Trichomes during Flowering Period Using 1H NMR-Based Metabolomics and Real-Time PCR

Abstract: Cannabis sativa trichomes are glandular structures predominantly responsible for the biosynthesis of cannabinoids, the biologically active compounds unique to this plant. To the best of our knowledge, most metabolomic works on C. sativa that have been reported previously focused their investigations on the flowers and leaves of this plant. In this study, 1H NMR-based metabolomics and real-time PCR analysis were applied for monitoring the metabolite profiles of C. sativa trichomes, variety Bediol, during the last 4 weeks of the flowering period. Partial least squares discriminant analysis models successfully classified metabolites of the trichomes based on the harvest time. Δ 9-Tetrahydrocannabinolic acid (1) and cannabidiolic acid (2) constituted the vital differential components of the organic preparations, while asparagine, glutamine, fructose, and glucose proved to be their water-extracted counterparts. According to RT-PCR analysis, gene expression levels of olivetol synthase and olivetolic acid cyclase influenced the accumulation of cannabinoids in the Cannabis trichomes during the monitoring time. Moreover, quantitative 1H NMR and RT-PCR analysis of the Cannabis trichomes suggested that the gene regulation of cannabinoid biosynthesis in the C. sativa variety Bediol is unique when compared with other C. sativa varieties.

Arctigenin Attenuates Learning and Memory Deficits through PI3k/Akt/GSK-3β Pathway Reducing Tau Hyperphosphorylation in Aβ-Induced AD Mice.

Abstract: Arctigenin is a phenylpropanoid dibenzylbutyrolactone lignan compound possessing antitumor, anti-inflammatory, anti-influenza, antioxidant, antibacterial, and hypoglycaemic activities. Our previous study demonstrated that arctigenin exerts neuroprotective effects both in vitro and in vivo in a Parkinsonʼs disease model. However, the exact mechanism through which arctigenin improves amyloid beta-induced memory impairment by inhibiting the production of the hyperphosphorylated tau protein is unknown. Amyloid β 1–42 was slowly administered via the intracerebroventricular route in a volume of 3 µL (≈ 410 pmmol/mouse) to mice. The mice were administered arctigenin (10, 40, or 150 mg/kg) or vehicle starting from the second day after amyloid β 1–42 injection to the end of the experiment. Behavioural tests were performed from days 9 to 15. On day 16 after the intracerebroventricular administration of amyloid β 1–42 , the mice were sacrificed for biochemical analysis. Arctigenin (10–150 mg/kg) significantly attenuated the impairment of spontaneous alternation behaviours in the Y-maze task, decreased the escape latency in the Morris water maze test, and increased the swimming times and swimming distances to the platform located in the probe test. Arctigenin attenuated the level of phosphorylated tau at the Thr-181, Thr-231, and Ser-404 sites in the hippocampus, and increased the phosphorylation levels of phosphatidylinositol-3-kinase, threonine/serine protein kinase B, and glycogen synthase kinase-3 β . Arctigenin effectively provides protection against learning and memory deficits and in inhibits hyperphosphorylated tau protein expression in the hippocampus. The possible mechanism may occur via the phosphatidylinositol-3-kinase/protein kinase B-dependent glycogen synthase kinase-3 β signalling pathway.

A First Step in the Quest for the Active Constituents in Filipendula ulmaria (Meadowsweet): Comprehensive Phytochemical Identification by Liquid Chromatography Coupled to Quadrupole-Orbitrap Mass Spectrometry.

Abstract: Filipendula ulmaria (meadowsweet) is traditionally used for the treatment of inflammatory diseases and as a diuretic and antirheumatic. Extracts of Filipendulae herba are on the market in the European Union as food supplements. Nevertheless, its active constituents remain to be revealed. During this study, the phytochemical composition of Filipendulae Ulmariae Herba was comprehensively characterised for the first time with two complementary generic ultrahigh-performance liquid chromatography-photodiode array-accurate mass mass spectrometry methods. Selective ion fragmentation experiments with a hybrid quadrupole-orbital trap mass spectrometer significantly contributed to compound identification: a total of 119 compounds were tentatively identified, 69 new to F. ulmaria. A rich diversity of phenolic constituents was detected and only a few non-phenolic phytochemicals were observed. Metabolisation and pharmacological studies should be conducted to investigate which of these constituents or metabolites there of contribute to the activity of F. ulmaria after oral intake.

New Dendrimer-Based Nanoparticles Enhance Curcumin Solubility.

Abstract: Curcumin, the main curcuminoid of the popular Indian spice turmeric, is a potent chemopreventive agent and useful in many different diseases. A major limitation of applicability of curcumin as a health promoting and medicinal agent is its extremely low bioavailability due to efficient first pass metabolism, poor gastrointestinal absorption, rapid elimination, and poor aqueous solubility. In the present study, nanotechnology was selected as a choice approach to enhance the bioavailability of the curcuminis. A new polyamidoamine dendrimer (G0.5) was synthesized, characterized, and tested for cytotoxicity in human breast cancer cells (MCF-7). No cytotoxicity of G0.5 was found in the range between 10−3 and 3 × 10−8 M. Consequently, G0.5 was used to prepare spherical nanoparticles of ca. 150 nm, which were loaded with curcumin [molar ratio G0.5/curcumin 1 : 1 (formulation 1) and 1 : 0.5 (formulation 2)]. Remarkably, the occurrence of a single population of nanoparticles having an excellent polydispersity index (

In Vitro Dermo-Cosmetic Evaluation of Bark Extracts from Common Temperate Trees

Abstract: Wood residues produced from forestry activities represent an interesting source of biologically active, high value-added secondary metabolites. In this study, 30 extracts from 10 barks of deciduous and coniferous tree species were investigated for their potential dermo-cosmetic use. The extracts were obtained from Fagus sylvatica, Quercus robur, Alnus glutinosa, Prunus avium, Acer pseudoplatanus, Fraxinus excelsior, Populus robusta, Larix decidua, Picea abies, and Populus tremula after three successive solid/liquid extractions of the barks with n-heptane, methanol, and methanol/water. All extracts were evaluated for their radical scavenging capacity, for their elastase, collagenase, and tyrosinase inhibitory activities, as well as for their antibacterial activity against gram-positive Staphylococcus aureus. In parallel, the global metabolite profiles of all extracts were established by 1D and 2D NMR and related to their biological activity. The results showed that the methanol extracts of Q. robur, A. glutinosa, L. decidua, and P. abies barks exhibit particularly high activities on most bioassays, suggesting their promising use as active ingredients in the dermo-cosmetic industry.

Anti-inflammatory Effect of Picrorhiza kurroa in Experimental Models of Inflammation.

Abstract: Picrorhiza kurroa is an important medicinal plant in the Ayurvedic system of medicine The root and rhizome of this plant are used for the treatment of various liver and inflammatory conditions In the present study, we sought to investigate the anti-inflammatory activity of P kurroa rhizome extract against carrageenan-induced paw edema and cotton pellet implantation-induced granuloma formation in rats In addition, its immunomodulatory activity was evaluated in Complete Freund's Adjuvant-induced stimulation of a peritoneal macrophage model and lipopolysaccharide-stimulated RAW 2647 murine macrophages Pretreatment with P kurroa rhizome extract inhibited carrageenan-induced paw edema and cotton pellet-induced granuloma formation in a dose-dependent manner This was associated with reduced levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) accompanied with increased anti-inflammatory cytokine (IL-10) in the serum and peritoneal macrophages Additionally, P kurroa rhizome extract inhibited inflammatory TNF-receptor 1 and cyclooxygenase-2 in Complete Freund's Adjuvant-induced activated peritoneal macrophages Furthermore, P kurroa rhizome extract treatment significantly inhibited iNOS and suppressed the activation of NF-κB through inhibition of its phosphorylation and by blocking the activation of IκB kinase alpha in lipopolysaccharide-stimulated RAW2647 macrophages Taken together, these results suggest that P kurroa has anti-inflammatory activity that is mediated through the suppression of macrophage-derived cytokine and mediators via suppression of NF-κB signaling

Pharmacokinetics of a Standardized Extract of Centella asiatica ECa 233 in Rats.

Abstract: ECa 233, a standardized extract of Centella asiatica, has been found to exhibit various positive neurological effects and to have a good safety profile. The present study aimed to explore the disposition kinetics of ECa 233, containing madecassoside (53.1 %) and asiaticoside (32.3 %), in rats. The extract was intravenously or orally administered at doses from 50 to 200 mg/kg. Plasma, tissues, urine, and feces were collected at time points from 0 to 48 h after dosing. The levels of madecassoside and asiaticoside, as well as their postulated triterpenic metabolites, madecassic acid and asiatic acid, in biological samples, were simultaneously measured by liquid chromatography-tandem mass spectrometry. The results showed that all animals had a good tolerability for ECa 233, whereas madecassic and asiatic acids were found in negligible amounts after pharmacokinetic assessment. Madecassoside and asiaticoside demonstrated rather similar absorption and tissue distribution profiles. They were rapidly absorbed, reaching maximum levels within 5–15 min after oral administration, but they had poor oral bioavailability, less than 1 %. Both triterpenoids were extensively distributed in the brain, stomach, and skin within 1 h and remained there for at least 4 h after dosing. Madecassoside and asiaticoside in ECa 233 were mainly excreted as an unchanged form after being injected, and exclusively as triterpenic acid metabolites in feces after oral administration. The pharmacokinetic results obtained could provide some guidance for an appropriate dosing regimen of ECa 233 in future studies. This study also provided the first evidence demonstrating the presence of madecassoside and asiaticoside in their target tissues.

Chemical Composition, Anticonvulsant Activity, and Toxicity of Essential Oil and Methanolic Extract of Elettaria cardamomum

Abstract: Elettaria cardamomum is an aromatic spice (cardamom) native to the humid Asian areas, which contains some compounds with a potential anticonvulsant activity. Various pharmacological properties such as anti-inflammatory, analgesic, antioxidant, and antimicrobial effects have been related to this plant. This research was conducted to examine the probable protective impact of the essential oil and methanolic extract of E. cardamomum against chemically (pentylentetrazole)- and electrically (maximal electroshock)-induced seizures in mice. In addition, neurotoxicity, acute lethality, and phytochemistry of the essential oil and methanolic extract were estimated. The TLC method showed the presence of kaempferol, rutin, and quercetin in the extract, and the concentration of quercetin in the extract was 0.5 µg/mL. The major compounds in the essential oil were 1,8-cineole (45.6 %), α-terpinyl acetate (33.7 %), sabinene (3.8 %), 4-terpinen-4-ol (2.4 %), and myrcene (2.2 %), respectively. The extract and essential oil showed significant neurotoxicity in the rotarod test at the doses of 1.5 g/kg and 0.75 mL/kg, respectively. No mortalities were observed up to the doses of 2 g/kg and 0.75 mL/kg for the extract and essential oil. The essential oil was effective in both the pentylentetrazole and maximal electroshock models; however, the extract was only effective in the pentylentetrazole model. The study suggested that E. cardamomum methanolic extract had no significant lethality in mice. Both the essential oil and methanolic extract showed movement toxicity. Anticonvulsant effects of E. cardamomum were negligible against the seizures induced by pentylentetrazole and maximal electroshock.