Metabolic fingerprinting of Cannabis sativa L., cannabinoids and terpenoids for chemotaxonomic and drug standardization purposes

Cannabis sativa L. is an important medicinal plant. In order to develop cannabis plant material as a medicinal product quality control and clear chemotaxonomic discrimination between varieties is a necessity. Therefore in this study 11 cannabis varieties were grown under the same environmental conditions. Chemical analysis of cannabis plant material used a gas chromatography flame ionization detection method that was validated for quantitative analysis of cannabis monoterpenoids, sesquiterpenoids, and cannabinoids. Quantitative data was analyzed using principal component analysis to determine which compounds are most important in discriminating cannabis varieties. In total 36 compounds were identified and quantified in the 11 varieties. Using principal component analysis each cannabis variety could be chemically discriminated. This methodology is useful for both chemotaxonomic discrimination of cannabis varieties and quality control of plant material.     

Plant protein-based hydrophobic fine and ultrafine carrier particles in drug delivery systems

For thousands of years, plants and their products have been used as the mainstay of medicinal therapy. In recent years, besides attempts to isolate the active ingredients of medicinal plants, other new applications of plant products, such as their use to prepare drug delivery vehicles, have been discovered. Nanobiotechnology is a branch of pharmacology that can provide new approaches for drug delivery by the preparation of biocompatible carrier nanoparticles (NPs). In this article, we review recent studies with four important plant proteins that have been used as carriers for targeted delivery of drugs and genes. Zein is a water-insoluble protein from maize; Gliadin is a 70% alcohol-soluble protein from wheat and corn; legumin is a casein-like protein from leguminous seeds such as peas; lectins are glycoproteins naturally occurring in many plants that recognize specific carbohydrate residues. NPs formed from these proteins show good biocompatibility, possess the ability to enhance solubility, and provide sustained release of drugs and reduce their toxicity and side effects. The effects of preparation methods on the size and loading capacity of these NPs are also described in this review.     

Exploring anti-TB leads from natural products library originated from marine microbes and medicinal plants

Multidrug-resistant tuberculosis (MDR-TB) and TB–HIV co-infection have become a great threat to global health. However, the last truly novel drug that was approved for the treatment of TB was discovered 40?years ago. The search for new effective drugs against TB has never been more intensive. Natural products derived from microbes and medicinal plants have been an important source of TB therapeutics. Recent advances have been made to accelerate the discovery rate of novel TB drugs including diversifying strategies for environmental strains, high-throughput screening (HTS) assays, and chemical diversity. This review will discuss the challenges of finding novel natural products with anti-TB activity from marine microbes and plant medicines, including biodiversity- and taxonomy-guided microbial natural products library construction, target- and cell-based HTS, and bioassay-directed isolation of anti-TB substances from traditional medicines.     

Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life

Background

The aim of this study was to describe the patterns of cannabis use and the associated benefits reported by patients with fibromyalgia (FM) who were consumers of this drug. In addition, the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users.

Methods

Information on medicinal cannabis use was recorded on a specific questionnaire as well as perceived benefits of cannabis on a range of symptoms using standard 100-mm visual analogue scales (VAS). Cannabis users and non-users completed the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI) and the Short Form 36 Health Survey (SF-36).

Results

Twenty-eight FM patients who were cannabis users and 28 non-users were included in the study. Demographics and clinical variables were similar in both groups. Cannabis users referred different duration of drug consumption; the route of administration was smoking (54%), oral (46%) and combined (43%). The amount and frequency of cannabis use were also different among patients. After 2 hours of cannabis use, VAS scores showed a statistically significant (p<0.001) reduction of pain and stiffness, enhancement of relaxation, and an increase in somnolence and feeling of well being. The mental health component summary score of the SF-36 was significantly higher (p<0.05) in cannabis users than in non-users. No significant differences were found in the other SF-36 domains, in the FIQ and the PSQI.

Conclusions

The use of cannabis was associated with beneficial effects on some FM symptoms. Further studies on the usefulness of cannabinoids in FM patients as well as cannabinoid system involvement in the pathophysiology of this condition are warranted.     

Zwitterionic glycosidase inhibitors: salacinol and related analogues

Natural products with interesting biological properties and structural diversity have often served as valuable lead drug candidates for the treatment of human diseases. Salacinol, a naturally occurring alpha-glucosidase inhibitor, was shown to be one of the active principles of the aqueous extract of a medicinal plant that has been prescribed traditionally as an Ayurvedic treatment for type II diabetes. Salacinol contains an intriguing zwitterionic sulfonium-sulfate structure that comprises a 1,4-anhydro-4-thio-D-arabinitol core and a polyhydroxylated acyclic chain. Due to the unique structural features and its potential to become a lead drug candidate in the treatment of type II diabetes, a great deal of attention has been focused on salacinol and its analogues. Since the isolation of salacinol, several papers describing various synthetic routes to salacinol and its analogues have appeared in the literature. This review is aimed at highlighting the synthetic aspects of salacinol and related compounds as well as their structure-activity relationship studies.     

Quantitative ethnobotany of two east Timorese cultures

This is the first time aspects of the ethnobotany of East Timor have been reported. The medicinal plant traditions of two distinct East Timorese cultures, the Laklei and Idate, were studied and compared using quantitative ethnobotanical methods. A total of 86 medicinal plant species were identified. The medicinal plant traditions of the Laklei and Idate cultures were compared using Trotter and Logan’s (1986) quantitative “informant agreement ratio.” On average, informant consensus was greater in Laklei, suggesting a medicinal plant tradition that is more defined than in Idate, where informants are more likely to use the same medicinal plants when treating the same usage categories. Furthermore, only 11 of the 86 medicinal plant species documented were used by both cultures, of which only six had similar mentions. These findings have important implications for the understanding of ethnobotany as they demonstrate how relatively closely situated cultural groups can have significantly different traditional knowledge systems.     

Cannabis use and the risk of developing a psychotic disorder

We briefly review the evidence that cannabis use in adolescence and young adulthood is a contributory cause of schizophreniform psychoses, by summarising longitudinal studies that: a) have examined relationships between cannabis use and the risk of psychosis or psychotic symptoms; and b) have controlled for potential confounders, such as other forms of drug use and personal characteristics that predict an increased risk of psychosis. There is now reasonable evidence from longitudinal studies that regular cannabis use predicts an increased risk of schizophrenia and of reporting psychotic symptoms. These relationships have persisted after controlling for confounding variables such as personal characteristics and other drug use. The relationships did not seem to be explained by cannabis being used to self-medicate symptoms of psychosis. A contributory causal relationship is biologically plausible because psychotic disorders involve disturbances in the dopamine neurotransmitter system with which the cannabinoid system interacts, as has been shown by animal studies and a human provocation study. We briefly explore the clinical and public health implications of the most plausible hypothesis, that cannabis use precipitates schizophrenia in persons who are vulnerable because of a personal or family history of schizophrenia.     

A review of natural products with antileishmanial activity.

Infections caused by protozoa of the genus Leishmania are a major worldwide health problem, with high endemicity in developing countries. The incidence of the disease has increased since the emergence of AIDS. In the absence of a vaccine, there is an urgent need for effective drugs to replace/supplement those in current use. The plant kingdom is undoubtedly valuable as a source of new medicinal agents. The present work constitutes a review of the literature on plant extracts and chemically defined molecules of natural origin showing antileishmanial activity. The review refers to 101 plants, their families, and geographical distribution, the parts utilized, the type of extract and the organism tested. It also includes 288 compounds isolated from higher plants and microorganisms, classified into appropriate chemical groups. Some aspects of recent antileishmanial-activity-directed research on natural products are discussed.     

Alkaloid-Poor Plant Families,Poaceae and Cyperaceae,Are Over-Utilized for Medicine in Hawaiian Pharmacopoeia

The theory of non-random medicinal plant selection predicts that the number of medicinal plant species in a given family is related to the total number of species in that family. As a consequence of such a strong relationship, some plant families are over-utilized for medicinal purposes while others are not. Medicinal plant families that are often over-utilized share evolutionary traits such as the presence of secondary plant compounds which are known to have medicinal values. Consistent with this model, several studies have shown that alkaloid-poor plant families such as Poaceae and Cyperaceae, two families known more for their physical defenses rather than their chemical defenses, are medicinally under-utilized across the world. In this study, we demonstrate that contrary to expectation, Poaceae and Cyperaceae are over-utilized in the Hawaiian ethnopharmacopoeia. One reason for this over-utilization is a result of the Hawaiian cultural practice of converting plants in the Poaceae and Cyperaceae families into ash for direct medicinal use or as a component in other medicinal preparations. The over-utilization of Poaceae and Cyperaceae is also potentially due to their versatility and greater availability in parts of the land divisions where most humans are allowed to visit. Knowledge of how to use ash is taught through mo‘olelo, Hawaiian history, and represents a Native Hawaiian understanding of and relationship to chemical knowledge. Our study provides new evidence for the theory of non-random medicinal plant selection and shows, contrary to expectation, that unique patterns of plant family over-utilization could arise in unique cultural and geographical contexts.     

Endophytic fungi isolated from medicinal plants: future prospects of bioactive natural products from Tabebuia/Handroanthus endophytes

Medicinal plants are a rich source of natural products used to treat many diseases; therefore, they are the basis for a new drug discovery. Plants are capable of generating different bioactive secondary metabolites, but a large amount of botanical material is often necessary to obtain small amounts of the target substance. Nowadays, many medicinal plants are becoming rather scarce. For this reason, it is important to point out the interactions between endophytic microorganisms and the host plant, because endophytes are able to produce highly diverse compounds, including those from host plants that have important biological activities. Thence, this review aims at presenting the richness in bioactive compounds of the medicinal plants from Tabebuia and Handroanthus genera, as well as important aspects about endophyte-plant interactions, with emphasis on the production of bioactive compounds by endophytic fungi, which has been isolated from various medicinal plants for such a purpose. Furthermore, bio-prospection of natural products synthesized by endophytes isolated from the aforementioned genera used in traditional medicine could be used to treat illnesses.

     

中国药用植物可持续利用战略框架简述

China is the birth-place of Traditional Chines Medicine (TCM) and has a rich diversity of medicinal plant resources. With the rapid increase in consumer demands for crude drugs and natural health products, many medicinal plant species are threatened with extinction from overexploitation and habitat destruction. To ensure the sustainable use of medicinal plant resources, we discuss in this article, a conservation framework consisting of conservation strategies, cultivation practices and various technologies. Conservation strategies include establishing in-situ and ex-situ conservation centers, setting up government policies and regulations, establishing methods for resource surveying and trade monitoring and establishing and enforcing Good Agricultural Practices (GAP). In terms of technologies, we use a remote multi-level sensing system and DNA barcoding technologies as examples to demonstrate their roles in the conservation and sustainable use of medicinal plant resources in China.     

Molluscan biological and chemical diversity: secondary metabolites and medicinal resources produced by marine molluscs

The phylum Mollusca represents an enormous diversity of species with eight distinct classes. This review provides a taxonomic breakdown of the published research on marine molluscan natural products and the medicinal products currently derived from molluscs, in order to identify priority targets and strategies for future research. Some marine gastropods and bivalves have been of great interest to natural products chemists, yielding a diversity of chemical classes and several drug leads currently in clinical trials. Molluscs also feature prominently in a broad range of traditional natural medicines, although the active ingredients in the taxa involved are typically unknown. Overall secondary metabolites have only been investigated from a tiny proportion (<1%) of molluscan species. At the class level, the number of species subject to chemical studies mirrors species richness and our relative knowledge of the biology of different taxa. The majority of molluscan natural products research is focused within one of the major groups of gastropods, the opisthobranchs (a subgroup of Heterobranchia), which are primarily comprised of soft‐bodied marine molluscs. Conversely, most molluscan medicines are derived from shelled gastropods and bivalves. The complete disregard for several minor classes of molluscs is unjustified based on their evolutionary history and unique life styles, which may have led to novel pathways for secondary metabolism. The Polyplacophora, in particular, have been identified as worthy of future investigation given their use in traditional South African medicines and their abundance in littoral ecosystems. As bioactive compounds are not always constitutively expressed in molluscs, future research should be targeted towards biosynthetic organs and inducible defence reactions for specific medicinal applications. Given the lack of an acquired immune system, the use of bioactive secondary metabolites is likely to be ubiquitous throughout the Mollusca and broadening the search field may uncover interesting novel chemistry.     

Medicinal biotechnology in the genus <Emphasis Type="Italic">scutellaria</Emphasis>

Plant-based medicines have an important role in the lives of millions of people. The ancient knowledge of the use of plants as medicines has led to the discovery of many important western pharmaceuticals, and the popularity of whole plant preparations for a range of therapeutic applications is growing rapidly. However, there are many challenges in the production of plant-based medicines, many of which put both the consumer and the plant populations at risk. Modern biotechnology can be optimized to mass-produce plants of specific chemical composition for use as particular treatments and applications. In this review, we have used one of the most important medicinal plant genera, Scutellaria, as a model to assess the potential of applications of biotechnology for the improvement of medicinal plants.     

The genetic manipulation of medicinal and aromatic plants

Medicinal and aromatic plants have always been intimately linked with human health and culture. Plant-derived medicines constitute a substantial component of present day human healthcare systems in industrialized as well as developing countries. They are products of plant secondary metabolism and are involved in many other aspects of a plant's interaction with its immediate environment. The genetic manipulation of plants together with the establishment of in vitro plant regeneration systems facilitates efforts to engineer secondary product metabolic pathways. Advances in the cloning of genes involved in relevant pathways, the development of high throughput screening systems for chemical and biological activity, genomics tools and resources, and the recognition of a higher order of regulation of secondary plant metabolism operating at the whole plant level facilitate strategies for the effective manipulation of secondary products in plants. Here, we discuss advances in engineering metabolic pathways for specific classes of compounds in medicinal and aromatic plants and we identify remaining constraints and future prospects in the field. In particular we focus on indole, tropane, nicotine, isoquinoline alcaloids, monoterpenoids such as menthol and related compounds, diterpenoids such as taxol, sequiterpenoids such as artemisinin and aromatic amino acids.     

Alterations of Monetary Reward and Punishment Processing in Chronic Cannabis Users: An fMRI Study

Alterations in reward and punishment processing have been reported in adults suffering from long-term cannabis use. However, previous findings regarding the chronic effects of cannabis on reward and punishment processing have been inconsistent. In the present study, we used functional magnetic resonance imaging (fMRI) to reveal the neural correlates of reward and punishment processing in long-term cannabis users (n = 15) and in healthy control subjects (n = 15) with no history of drug abuse. For this purpose, we used the well-established Monetary Incentive Delay (MID) task, a reliable experimental paradigm that allows the differentiation between anticipatory and consummatory aspects of reward and punishment processing. Regarding the gain anticipation period, no significant group differences were observed. In the left caudate and the left inferior frontal gyrus, cannabis users were – in contrast to healthy controls – not able to differentiate between the conditions feedback of reward and control. In addition, cannabis users showed stronger activations in the left caudate and the bilateral inferior frontal gyrus following feedback of no punishment as compared to healthy controls. We interpreted these deficits in dorsal striatal functioning as altered stimulus-reward or action-contingent learning in cannabis users. In addition, the enhanced lateral prefrontal activation in cannabis users that is related to non-punishing feedback may reflect a deficit in emotion regulation or cognitive reappraisal in these subjects.     

Process strategies for plant cell cultures

Plants synthesize a tremendously wide range of chemical structures, many of which have been used over the centuries to the benefit of mankind. Today, with attention again turning to the plant kingdom as a source of drugs, food additives, perfumes and so on, a further dimension has been added to traditional methods of synthesis of these products: the use of cultured plant cells. Although plant cell culture technology is perhaps still in its infancy compared with other aspects of biotechnology, an extensive information and experience base is being established for the development of plant cell processes. The establishment of such a foundation is important for the application of plant cell technology in the years ahead.     

Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants

Natural products represent a significant reservoir of unexplored chemical diversity for early-stage drug discovery. The identification of lead compounds of natural origin would benefit from therapeutically relevant bioassays capable of facilitating the isolation of bioactive molecules from multi-constituent extracts. Towards this end, we developed an in vivo bioassay-guided isolation approach for natural product discovery that combines bioactivity screening in zebrafish embryos with rapid fractionation by analytical thin-layer chromatography (TLC) and initial structural elucidation by high-resolution electrospray mass spectrometry (HRESIMS). Bioactivity screening of East African medicinal plant extracts using fli-1:EGFP transgenic zebrafish embryos identified Oxygonum sinuatum and Plectranthus barbatus as inhibiting vascular development. Zebrafish bioassay-guided fractionation identified the active components of these plants as emodin, an inhibitor of the protein kinase CK2, and coleon A lactone, a rare abietane diterpenoid with no previously described bioactivity. Both emodin and coleon A lactone inhibited mammalian endothelial cell proliferation, migration, and tube formation in vitro, as well as angiogenesis in the chick chorioallantoic membrane (CAM) assay. These results suggest that the combination of zebrafish bioassays with analytical chromatography methods is an effective strategy for the rapid identification of bioactive natural products.     

The molecular mechanisms that underpin the biological benefits of full-spectrum cannabis extract in the treatment of neuropathic pain and inflammation

Cannabis has been shown to be beneficial in the treatment of pain and inflammatory diseases. The biological effect of cannabis is mainly attributed to two major cannabinoids, tetrahydrocannabinol and cannabidiol. In the majority of studies to-date, a purified tetrahydrocannabinol and cannabidiol alone or in combination have been extensively examined in many studies for the treatment of numerous disorders including pain and inflammation. However, few studies have investigated the biological benefits of full-spectrum cannabis plant extract. Given that cannabis is known to generate a large number of cannabinoids along with numerous other biologically relevant products including terpenes, studies involving purified tetrahydrocannabinol and/or cannabidiol do not consider the potential biological benefits of the full-spectrum cannabis extracts. This may be especially true in the case of cannabis as a potential treatment of pain and inflammation. Herein, we review the pre-clinical physiological and molecular mechanisms in biological systems that are affected by cannabis.