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Journal ArticleDOI

Cannabis sativa: The Plant of the Thousand and One Molecules

04 Feb 2016-Frontiers in Plant Science (Frontiers Media SA)-Vol. 7, pp 19-19
TL;DR: Prospects on the benefits linked to the use of the -omics technologies, such as metabolomics and transcriptomics to speed up the identification and the large-scale production of lead agents from bioengineered Cannabis cell culture, are presented.
Abstract: Cannabis sativa L. is an important herbaceous species originating from Central Asia, which has been used in folk medicine and as a source of textile fiber since the dawn of times. This fast-growing plant has recently seen a resurgence of interest because of its multi-purpose applications: it is indeed a treasure trove of phytochemicals and a rich source of both cellulosic and woody fibers. Equally highly interested in this plant are the pharmaceutical and construction sectors, since its metabolites show potent bioactivities on human health and its outer and inner stem tissues can be used to make bioplastics and concrete-like material, respectively. In this review, the rich spectrum of hemp phytochemicals is discussed by putting a special emphasis on molecules of industrial interest, including cannabinoids, terpenes and phenolic compounds, and their biosynthetic routes. Cannabinoids represent the most studied group of compounds, mainly due to their wide range of pharmaceutical effects in humans, including psychotropic activities. The therapeutic and commercial interests of some terpenes and phenolic compounds, and in particular stilbenoids and lignans, are also highlighted in view of the most recent literature data. Biotechnological avenues to enhance the production and bioactivity of hemp secondary metabolites are proposed by discussing the power of plant genetic engineering and tissue culture. In particular two systems are reviewed, i.e., cell suspension and hairy root cultures. Additionally, an entire section is devoted to hemp trichomes, in the light of their importance as phytochemical factories. Ultimately, prospects on the benefits linked to the use of the -omics technologies, such as metabolomics and transcriptomics to speed up the identification and the large-scale production of lead agents from bioengineered Cannabis cell culture, are presented.

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Citations
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Journal ArticleDOI
TL;DR: This review highlights the pharmacological activities of CBD, its cannabinoid receptor-dependent and -independent action, its biological effects focusing on immunomodulation, angiogenetic properties, and modulation of neuronal and cardiovascular function, and the therapeutic potential of cannabidiol.

381 citations

Journal ArticleDOI
TL;DR: The study provides perspectives on the use of Si to increase the yield of fiber crops and to improve the thermal stability and tensile strength of natural fibers and to modify/improve the physical parameters of plant fibers.
Abstract: Elemental silicon (Si), after oxygen, is the second most abundant element in the earth’s crust, which is mainly composed of silicates. Si is not considered essential for plant growth and development, however increasing evidence in the literature shows that this metalloid is beneficial to plants, especially under stress conditions. Indeed Si alleviates the toxic effects caused by abiotic stresses, e.g. salt stress, drought, heavy metals, to name a few. Biogenic silica is also a deterrent against herbivores. Additionally, Si ameliorates the vigour of plants and improves their resistance to exogenous stresses. The protective role of Si was initially attributed to a physical barrier fortifying the cell wall (e.g. against fungal hyphae penetration), however several studies have shown that the action of this element on plants is far more complex, as it involves a cross-talk with the cell interior and an effect on plant metabolism. In this study the beneficial role of Si on plants will be discussed, by reviewing the available data in the literature. Emphasis will be given to the protective role of Si during (a)biotic stresses and in this context both priming and the effects of Si on endogenous phytohormones will be discussed. A whole section will be devoted to the use of silica (SiO2) nanoparticles, in the light of the interest that nanotechnology has for agriculture. The paper also discusses the potential technological aspects linked to the use of Si in agriculture and to modify/improve the physical parameters of plant fibers. The study indeed provides perspectives on

359 citations


Cites background from "Cannabis sativa: The Plant of the T..."

  • ...Fiber crops like textile hemp (Cannabis sativa L.) are natural resources which provide long and strong cellulosic fibers (a.k.a. bast fibers) used in both the textile and biocomposite sectors (Guerriero et al., 2014; Andre et al., 2016; Guerriero et al., 2016b)....

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Journal ArticleDOI
TL;DR: A deeper involvement of phytocannabinoids (the key compounds in C. sativa) in several others central and peripheral pathophysiological mechanisms such as food intake, inflammation, pain, colitis, sleep disorders, neurological and psychiatric illness is suggested.

315 citations

Journal ArticleDOI
TL;DR: In this paper, the effects of heavy metal-induced reactive oxygen species (ROS) on plant cell wall-related processes and the stimulatory/inhibitory effects of ROS on plant secondary metabolism were investigated.

254 citations

Journal ArticleDOI
TL;DR: A large retrospective case series involving clinical application of CBD for anxiety and sleep complaints as an adjunct to usual treatment found CBD was well tolerated in all but 3 patients.
Abstract: Context Cannabidiol (CBD) is one of many cannabinoid compounds found in cannabis. It does not appear to alter consciousness or trigger a “high.” A recent surge in scientific publications has found preclinical and clinical evidence documenting value for CBD in some neuropsychiatric disorders, including epilepsy, anxiety, and schizophrenia. Evidence points toward a calming effect for CBD in the central nervous system. Interest in CBD as a treatment of a wide range of disorders has exploded, yet few clinical studies of CBD exist in the psychiatric literature.

252 citations

References
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Journal ArticleDOI
TL;DR: This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003 and is able to identify only one de novo combinatorial compound approved as a drug in this 25 plus year time frame.
Abstract: This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003. In the case of all approved agents the time frame has been extended to include the 251/2 years from 01/1981 to 06/2006 for all diseases worldwide and from 1950 (earliest so far identified) to 06/2006 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a “natural product mimic” or “NM” to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 155 small molecules, 73% are other than “S” (synthetic), with 47% actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the antiinfective area ...

5,170 citations

Journal ArticleDOI
TL;DR: This review is an updated and expanded version of the three prior reviews and adds a new designation, "natural product botanical" or "NB", to cover those botanical "defined mixtures" that have now been recognized as drug entities by the FDA and similar organizations.
Abstract: This review is an updated and expanded version of the three prior reviews that were published in this journal in 1997, 2003, and 2007. In the case of all approved therapeutic agents, the time frame has been extended to cover the 30 years from January 1, 1981, to December 31, 2010, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2010 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a “natural product mimic” or “NM” to join the original primary divisions and have added a new designation, “natural product botanical” or “NB”, to cover those botanical “defined mixtures” that have now been recognized as drug entities by the FDA and similar organizations. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 175 small molecules, 131, or 74...

4,271 citations

Journal ArticleDOI
TL;DR: The present findings do not authenticate the involvement of F. mangiferae in the disease, however hormonal imbalance, most probably ethylene, might be responsible for deformed functional morphology of panicle and a signal transduction mechanism of stress-stimulated ethylene imbalance causing physio-morphological changes in reproductive organs of mango flower and thereby failure of fertilization and fruit set needs to be investigated.
Abstract: Mango malformation is the most important and threatening disease of recent times, primarily because of persistent lacuna in complete understanding of its nature. Diverse Fusarium spp, including F. mangiferae, were found to be associated with the disease. Here, F. mangiferae from mango cv Dashehri was morphologically characterized. Typically, oval-shaped microconidia without septum and crescent-shaped macroconidia with 3-septate were more often observed, whereas not a single chlamydospore was detected. The length and width of micro- and macro-conidia were 7.5, 55, 3.2, and 3.5, respectively. The plant growth regulators such as NAA, GA3, BAP and ethrel were found to induce in vitro germination of conidia of F. mangiferae after 12 h. In contrast, antimalformin silver nitrate (AgNO3) inhibits conidial germination in vitro and none of conidia was germinated beyond 500 ppm, however antimalformin glutathione was highly effective in stimulating conidial germination of F. mangiferae in vitro at > 1000 ppm after 24 h. We observed that the response of F. mangiferae to germinate the conidia in vitro under influence of plant growth regulators and antimalformins is not coincided with earlier findings of reduced disease incidence by exogenous application of these compounds. The present findings do not authenticate the involvement of F. mangiferae in the disease, however hormonal imbalance, most probably ethylene, might be responsible for deformed functional morphology of panicle. Further, a signal transduction mechanism of stress-stimulated ethylene imbalance causing physio-morphological changes in reproductive organs of mango flower and thereby failure of fertilization and fruit set, which needs to be investigated.

2,202 citations

Journal ArticleDOI
TL;DR: As marijuana use becomes legal in some states, the dominant public opinion is that marijuana is a harmless source of mood alteration, but enough information is available to cause concern.
Abstract: As marijuana use becomes legal in some states, the dominant public opinion is that marijuana is a harmless source of mood alteration. Although the harms associated with marijuana use have not been well studied, enough information is available to cause concern.

2,069 citations


"Cannabis sativa: The Plant of the T..." refers background in this paper

  • ...Two recent reviews (Volkow et al., 2014; van Amsterdam et al., 2015) notably reported the adverse health effects linked to the use of natural Cannabis and synthetic cannabinoids, respectively....

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Journal ArticleDOI
TL;DR: A comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy is provided.
Abstract: The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson9s and Huntington9s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB 1 receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB 1 receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB 2 receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients9 need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.

1,857 citations


"Cannabis sativa: The Plant of the T..." refers background in this paper

  • ...The sum of the THC and CBD fractions (without reporting the distinct amounts of each of them) in hemp stem wood and bark extractives was 2 and 1%, respectively, which represented 0.003 and 0.0005% of the total fiber content....

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  • ...The pharmacology of phytocannabinoids has previously been reviewed elsewhere (Pacher et al., 2006; Russo, 2011; Hill et al., 2012; Giacoppo et al., 2014; Burstein, 2015) and a brief summary and update will be presented hereafter....

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  • ...But THC has actually more molecular targets than just CB1 and CB2 receptors, and exhibit potent anti-inflammatory, anti-cancer, analgesic, muscle relaxant, neuro-antioxidative (De Petrocellis et al., 2011), and antispasmodic activities (Pacher et al., 2006)....

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