RESUMO
While Cannabis sativa L. varieties have been traditionally characterized by their major cannabinoid profile, it is now well established that other plant metabolites can also have physiological effects, including minor cannabinoids, terpenes, and flavonoids. Given the multiple applications of cannabis in the medical field, it is therefore critical to characterize it according to its chemical composition (i.e., its metabolome) and not only its botanical traits. With this in mind, the cannabinoid and metabolomic profiles from inflorescences of two C. sativa varieties with either high Δ9-tetrahydrocannabinolic acid (THCA) or high cannabidiolic acid (CBDA) contents harvested at different times were studied. According to results from HPLC and NMR-based untargeted metabolomic analyses of organic and aqueous plant material extracts, we show that in addition to expected variations according to cannabinoid profiles, it is possible to distinguish between harvests of the same variety. In particular, it was possible to correlate variations in the metabolome with presence of powdery mildew, leading to the identification of molecular markers associated with this fungal infection in C. sativa.
RESUMO
Over the past few years, considerable attention has focused on cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the two major constituents of Cannabis sativa, mainly due to the promising potential medical uses they have shown. However, more information on the fate of these cannabinoids in human subjects is still needed and there is limited research on the pharmacokinetic drug-drug interactions that can occur in the clinical setting and their prevalence. As the use of cannabinoids is substantially increasing for many indications and they are not the first-line therapy in any treatment, health care professionals must be aware of drug-drug interactions during their use as serious adverse events can happen related with toxic or ineffective outcomes. The present chapter overview summarizes our current knowledge on the pharmacokinetics and metabolic fate of CBD and THC in humans and discusses relevant drug-drug interactions, giving a plausible explanation to facilitate further research in the area.
Assuntos
Canabinoides , Preparações Farmacêuticas , Canabidiol , Canabinoides/efeitos adversos , Dronabinol , Interações Medicamentosas , HumanosRESUMO
Cholesterol is a C27-sterol employed as starting material for the synthesis of valuable pharmaceutical steroids and precursors. The microbial transformations of cholesterol have been widely studied, since they are performed with high regio- and stereoselectivity and allow the production of steroidal compounds which are difficult to synthesize by classical chemical methods. In recent years, ongoing research is being conducted to discover novel biocatalysts and to develop biotechnological processes to improve existing biocatalysts and biotransformation reactions. The main objective of this review is to present the most remarkable advances in fungal and bacterial transformation of cholesterol, focusing on the different types of microbial reactions and biocatalysts, biotransformation products, and practical aspects related to sterol dispersion improvement, covering literature since 2000. It reviews the conversion of cholesterol by whole-cell biocatalysts and by purified enzymes that lead to various structural modifications, including side chain cleavage, hydroxylation, dehydrogenation/reduction, isomerization and esterification. Finally, approaches used to improve the poor solubility of cholesterol in aqueous media, such as the use of different sterol-solubilizing agents or two-phase conversion system, are also discussed.
Assuntos
Bactérias/metabolismo , Biotecnologia/métodos , Colesterol/metabolismo , Fungos/metabolismo , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Biotecnologia/tendências , Biotransformação , Enzimas/metabolismo , Fungos/genética , Fungos/crescimento & desenvolvimentoRESUMO
The use of Cannabis for medical purposes is rapidly expanding and is usually employed as a self-medication for the treatment of insomnia disorder. However, the effect on sleep seems to depend on multiple factors such as composition of the Cannabis, dosage and route of administration. Vaporization is the recommended route for the administration of Cannabis for medical purposes; however, there is no published research about the effects of vaporized Cannabis on sleep, neither in laboratory animals, nor in humans. Because previous reports suggested that low doses of THC have sedating effects, the aim of the present study was to characterize in rats, the acute effects on sleep induced by the administration of low doses of THC by means of vaporization of a specific type of Cannabis (THC 11.5% and negligible amounts of other cannabinoids). For this purpose, polysomnographic recordings in chronically prepared rats were performed during 6â¯h in the light and dark phases. Animals were treated with 0 (control), 40, 80 and 200â¯mg of Cannabis immediately before the beginning of recordings; the THC plasma concentrations with these doses were low (up to 6.7â¯ng/mL with 200â¯mg). A quantitative EEG analyses by means of the spectral power and coherence estimations was also performed for the highest Cannabis dose. Compared to control, 200â¯mg of Cannabis increased NREM sleep time during the light phase, but only during the first hour of recording. Interestingly, no changes on sleep were observed during the dark (active) phase or with lower doses of Cannabis. Cannabis 200â¯mg also produced EEG power reductions in different cortices, mainly for high frequency bands during W and REM sleep, but only during the light phase. On the contrary, a reduction in the sleep spindles intra-hemispheric coherence was observed during NREM sleep, but only during the dark phase. In conclusion, administration of low doses of THC by vaporization of a specific type of Cannabis produced a small increment of NREM sleep, but only during the light (resting) phase. This was accompanied by subtle modifications of high frequency bands power (during the light phase) and spindle coherence (during the dark phase), which are associated with cognitive processing. Our results reassure the importance of exploring the sleep-promoting properties of Cannabis.
Assuntos
Cannabis , Córtex Cerebral/fisiologia , Sono , Eletroencefalografia , Humanos , Sono REM , VolatilizaçãoRESUMO
Microorganisms were isolated from industrial wool scouring effluents and from the soil adjacent to the wastewater treatment lagoon, both sterols-rich environments, in order to search for novel biocatalysts able to transform cholesterol. The isolates were identified on the basis of morphological and biochemical characteristics and phylogenetic analysis. Furthermore, a rapid and accurate bacteria identification by matrix assisted laser desorption/ionization-time-of-flight mass spectrometry was carried out. Bacteria and fungi including representatives of the genera Fusarium, Talaromyces, Trichoderma, Mucor, Aspergillus, Citrobacter, Proteus, Klebsiella, Exiguobacterium, Acinetobacter, Tsukamurella, Bacillus, and Streptomyces were found and evaluated for their ability to biotransform cholesterol by whole-cell treatment system. The results show that a Trichoderma koningiopsis strain, as well as two strains of Mucor circinelloides were able to transform cholesterol into value-added products. The major products were characterized as 7ß-hydroxycholesterol, 4-cholesten-3-one, 5α,6α-epoxycholestan-3ß-ol and 5ß,6ß-epoxycholestan-3ß-ol. To the best of our knowledge, the present study is the first report of cholesterol biotransformation by representatives of Trichoderma and Mucor genera.