No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads
Abstract
The golden age of cannabis pharmacology began in the 1960s as Raphael Mechoulam and his colleagues in Israel isolated and synthesized cannabidiol, tetrahydrocannabinol, and other phytocannabinoids. Initially, THC garnered most research interest with sporadic attention to cannabidiol, which has only rekindled in the last 15 years through a demonstration of its remarkably versatile pharmacology and synergy with THC. Gradually a cognizance of the potential of other phytocannabinoids has developed. Contemporaneous assessment of cannabis pharmacology must be even far more inclusive. Medical and recreational consumers alike have long believed in unique attributes of certain cannabis chemovars despite their similarity in cannabinoid profiles. This has focused additional research on the pharmacological contributions of mono- and sesquiterpenoids to the effects of cannabis flower preparations. Investigation reveals these aromatic compounds to contribute modulatory and therapeutic roles in the cannabis entourage far beyond expectations considering their modest concentrations in the plant. Synergistic relationships of the terpenoids to cannabinoids will be highlighted and include many complementary roles to boost therapeutic efficacy in treatment of pain, psychiatric disorders, cancer, and numerous other areas. Additional parts of the cannabis plant provide a wide and distinct variety of other compounds of pharmacological interest, including the triterpenoid friedelin from the roots, canniprene from the fan leaves, cannabisin from seed coats, and cannflavin A from seed sprouts. This chapter will explore the unique attributes of these agents and demonstrate how cannabis may yet fulfil its potential as Mechoulam's professed “pharmacological treasure trove.”
... In addition to the most predominant cannabinoids in cannabis, delta-9-tetrahydrocannabinol (D9-THC) and cannabidiol (CBD), cannabis products also contain other, less abundant cannabinoids such as tetrahydrocannabivarin (THCV), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), and terpenes. 1,2 Terpenes in cannabis of particular interest included in the current studies are D-limonene, a-pinene, a-terpineol, bisabolol, and b-caryophyllene. ...
... 3 D8-THC can also be synthesized in the laboratory via conversion from hemp-extracted CBD. 4 Cannabinoids and terpenes interact with cell membranes, neurotransmitter receptors, G-protein coupled receptors, second messenger systems, and enzymes, and are theorized to contribute to the therapeutic effects of cannabis and to mitigate some of the unwanted effects of D9-THC (i.e., the ''entourage effect''). 1,2 With selective breeding and refined extraction processes, products that have specific cannabinoid and terpene profiles are being developed and marketed for specific medical conditions and pharmacological effects. There is growing interest in cannabinoids and terpenes as novel therapeutics for treating a range of neuropsychiatric disorders, including anxiety. ...
... There is growing interest in cannabinoids and terpenes as novel therapeutics for treating a range of neuropsychiatric disorders, including anxiety. 1,2,5 Cannabinoids other than D9-THC that are naturally present in cannabis are termed ''minor'' cannabinoids. Many of the minor cannabinoids display pharmacology that is similar to D9-THC, in that they act as a partial agonists at cannabinoid type 1 receptors (CB1R) and cannabinoid type 2 receptors (CB2R). ...
Background: Cannabis and its primary psychoactive constituent delta-9-tetrahydrocannabinol (D9-THC) produce biphasic, dose-dependent effects on anxiety. In addition to D9-THC, cannabis contains other “minor” cannabinoids and terpenes with purported therapeutic potential for the treatment of anxiety. Empirical data on potential therapeutic effects of these compounds is limited. The current study evaluated the effects of selected minor cannabinoids and terpenes in a battery of tests sensitive to anxiolytic and anxiogenic drugs.
Methods: In Experiment 1, adult male Sprague Dawley rats (N=7–8/group) were administered acute oral doses of one of five minor cannabinoids: delta-8-tetrahydrocannabinol (D8-THC; 10 mg/kg), tetrahydrocannabivarin (32 mg/kg), cannabidiolic acid (32 mg/kg), cannabidivarin (32 mg/kg), and cannabigerol (100 mg/kg), or one of five terpenes: D-limonene (17 mg/kg), ⍺-pinene (100 mg/kg), ⍺-terpineol (10 mg/kg), bisabolol (100 mg/kg), and β-caryophyllene (17 mg/kg), or vehicle (medium-chain triglycerides [MCT] oil). Ethyl alcohol was tested as an active comparator. Thirty minutes post-administration, the marble burying test, the three-chamber social interaction test, and the novelty-induced hypophagia test were completed; motor activity was assessed throughout testing. Experiment 2 examined the potential anxiolytic effects of minor cannabinoids when administered chronically; rats administered MCT oil or minor cannabinoids in Experiment 1 continued receiving once-daily doses for 21 days and were assessed using the same test battery after 7, 14, and 21 days of administration.
Results and Conclusions: When compared to vehicle, acute administration of bisabolol and D-limonene increased the amount of food consumed and bisabolol-, D-limonene-, ⍺-pinene-, and β-caryophyllene decreased percent time spent in the outer zone in the novelty-induced hypophagia test, suggestive of an anxiolytic effect. Only ethanol increased social interaction. After acute administration, anxiogenic effects in the marble burying test were observed for D8-THC, but not for other minor cannabinoids and terpenes. Throughout chronic administration, only D8-THC displayed anxiogenic effects in the novelty-induced hypophagia test. The other cannabinoids did not show anxiolytic or anxiogenic effects in any of the tests at the doses or times tested. The minor cannabinoids and terpenes did not impair or stimulate general motor activity. These data provide a foundation for future studies investigating cannabinoid/terpene interactions.
... Anti-pain, anti-inflammatory, hepatoprotective, analgesic, antioxidant, neuroprotective, gastroprotective, antinociceptive, anticancer, antidiabetic [32][33][34]43,44] β/α-caryophyllene Antibacterial, antifungal, antioxidant, anti-inflammatory, anticancer, anxiolytic [40,43] α/β-pinene Antimetastatic, anti-inflammatory, antibacterial, antidepressant, anticancer [33,34,40] D-limonene Anxiolytic, immunostimulatory, anticancer [32,34] Linalool Sedative, antiepileptic [34] Terpineol Antinociceptive, antifungal, anti-inflammatory, antidiarrheal [43] Bisabolol Anticancer [33] β-ocimene Anticonvulsant, anticancer, antifungal [26] 6 of 21 Biomolecules 2023, 13, x FOR PEER REVIEW 6 of 25 Figure 3. Chemical structure of the main terpenes found in C. sativa. ...
... Anti-pain, anti-inflammatory, hepatoprotective, analgesic, antioxidant, neuroprotective, gastroprotective, antinociceptive, anticancer, antidiabetic [32][33][34]43,44] β/α-caryophyllene Antibacterial, antifungal, antioxidant, anti-inflammatory, anticancer, anxiolytic [40,43] α/β-pinene Antimetastatic, anti-inflammatory, antibacterial, antidepressant, anticancer [33,34,40] D-limonene Anxiolytic, immunostimulatory, anticancer [32,34] Linalool Sedative, antiepileptic [34] Terpineol Antinociceptive, antifungal, anti-inflammatory, antidiarrheal [43] Bisabolol Anticancer [33] β-ocimene Anticonvulsant, anticancer, antifungal [26] 6 of 21 Biomolecules 2023, 13, x FOR PEER REVIEW 6 of 25 Figure 3. Chemical structure of the main terpenes found in C. sativa. ...
... Pharmacological Effects Refs β-myrcene Anti-pain, anti-inflammatory, hepatoprotective, analgesic, antioxidant, neuroprotective, gastroprotective, antinociceptive, anticancer, antidiabetic [32][33][34]43,44] β/α-caryophyllene Antibacterial, antifungal, antioxidant, antiinflammatory, anticancer, anxiolytic [40,43] α/β-pinene Antimetastatic, anti-inflammatory, antibacterial, antidepressant, anticancer [33,34,40] D-limonene Anxiolytic, immunostimulatory, anticancer [32,34] Linalool Sedative, antiepileptic [34] Terpineol Antinociceptive, antifungal, anti-inflammatory, antidiarrheal [43] Bisabolol Anticancer [33] β-ocimene Anticonvulsant, anticancer, antifungal [26] 3 ...
Cannabis sativa is a multipurpose plant that has been used in medicine for centuries. Recently, considerable research has focused on the bioactive compounds of this plant, particularly cannabinoids and terpenes. Among other properties, these compounds exhibit antitumor effects in several cancer types, including colorectal cancer (CRC). Cannabinoids show positive effects in the treatment of CRC by inducing apoptosis, proliferation, metastasis, inflammation, angiogenesis, oxidative stress, and autophagy. Terpenes, such as β-caryophyllene, limonene, and myrcene, have also been reported to have potential antitumor effects on CRC through the induction of apoptosis, the inhibition of cell proliferation, and angiogenesis. In addition, synergy effects between cannabinoids and terpenes are believed to be important factors in the treatment of CRC. This review focuses on the current knowledge about the potential of cannabinoids and terpenoids from C. sativa to serve as bioactive agents for the treatment of CRC while evidencing the need for further research to fully elucidate the mechanisms of action and the safety of these compounds.
... Following Russo's publication on the subject [1], the focus has been extended to include terpenes among cannabis Active Pharmaceutical Ingredients (APIs). The potential therapeutic benefits related to cannabinoidsterpenes combinations were suggested to various physiological systems [1][2][3][4][5][6]. Consequently, a growing number of studies and caregiving instructions dealing with medical cannabis use terms such as "full preparations containing dozens of APIs, many of which may contribute to the effect of medical cannabis on ECS-controlled physiological functions. ...
... 2 Estimated based on the solubility of similar terpenes. 3 Reagents used in prior reports were dissolved in aqueous solutions containing salts ("physiological solutions") and/or residues of solvents used to form stock solutions, out of which the solutions to be tested were formed. The assumption made here is that, since the concentrations of those solutes are relatively small (under 1%), the solubility of the reagents in the reported solutions are similar to those in water. ...
... 4A.2 Not determined because of the low solubility of the terpene at 10 µM.3 Effect was defined wherein a significant main effect of condition (i.e., CB1 response obtained by THC and terpene at 1:10 ratio > CB1 response obtained by THC alone, p < 0.05, two-ways ANOVA) was demonstrated ...
The cannabis plant exerts its pharmaceutical activity primarily by the binding of cannabinoids to two G protein-coupled cannabinoid receptors, CB1 and CB2. The role that cannabis terpenes play in this activation has been considered and debated repeatedly, based on only limited experimental results. In the current study we used a controlled in-vitro heterologous expression system to quantify the activation of CB1 receptors by sixteen cannabis terpenes individually, by tetrahydrocannabinol (THC) alone and by THC-terpenes mixtures. The results demonstrate that all terpenes, when tested individually, activate CB1 receptors, at about 10-50% of the activation by THC alone. The combination of some of these terpenes with THC significantly increases the activity of the CB1 receptor, compared to THC alone. In some cases, several fold. Importantly, this amplification is evident at terpene to THC ratios similar to those in the cannabis plant, which reflect very low terpene concentrations. For some terpenes, the activation obtained by THC- terpene mixtures is notably greater than the sum of the activations by the individual components, suggesting a synergistic effect. Our results strongly support a modulatory effect of some of the terpenes on the interaction between THC and the CB1 receptor. As the most effective terpenes are not necessarily the most abundant ones in the cannabis plant, reaching "whole plant" or "full spectrum" composition is not necessarily an advantage. For enhanced therapeutic effects, desired compositions are attainable by enriching extracts with selected terpenes. These compositions adjust the treatment for various desired medicinal and personal needs.
... Medicinal and cultural use of Cannabis sativa has been dated to the Neolithic period in central Asia (~4,000 BC), where it was used to boost cognition, longevity, and treat senility (amongst other applications) (Bonini et al., 2018;Sinclair, 2020). Cannabis contains >550 phytochemicals including >100 phytocannabinoids and other compounds, such as terpenes and flavonoids, that can act on the central nervous system and ECS and may have important therapeutic potential for AD pathophysiology and its clinical management (Lewis et al., 2017;Rock & Parker, 2021;Russo, 2011;Russo, 2018;Russo & Marcu, 2017) providing vital potential drug discovery pathways (Gonçalves et al., 2020;Salminen et al., 2008). Further, when combined (such as in a botanical extract), the combination of these phytochemicals may promote the synergistic 'entourage effect', which may improve efficacy and reduce side effects (Russo, 2011;Russo, 2019;Anand, 2021). ...
... Terpenes are naturally occurring constituents found in many plant species, including cannabis, citrus fruits, thyme, and tea. Being the odorous compounds isolated from essential oils, terpenes are responsible for the aroma and flavour of Cannabis sativa (Cox-Georgian et al., 2019;Paduch et al., 2007;Rock & Parker, 2021;Russo & Marcu, 2017). To date, 120 different terpene compounds have been extracted from Cannabis sativa (Rock & Parker, 2021). ...
... For example, formulations rich in non-intoxicating cannabinoids that promote anti-inflammatory effects such as CBD, CBG, CBN and antioxidant-rich terpenes and flavonoids may be relevant to prevention and prophylaxis in preclinical and prodromal phases of AD. In contrast, THC formulations may be more relevant for moderate to later stage AD where the management of noncognitive symptoms such as BPSD are a priority (Bahji et al., 2020;Charernboon et al., 2021;Hillen et al., 2019;Russo, 2018;Russo & Marcu, 2017). Second, the administration route should be considered given the slow release and low bioavailability of oral formulations, which may be more preferrable to managing chronic symptoms, rather than acute symptoms such as break-through pain or aggression (Boehnke et al., 2019;Cranford et al., 2016;MacCallum & Russo, 2018). ...
Alzheimer's disease (AD) is the most common form of dementia, and currently there is no cure. New therapeutic strategies that have the potential to address the complex pathophysiology of AD are urgently required; medicinal cannabis offers this possibility. Several potential leads can be extracted from Cannabis sativa (cannabis) that can target AD pathophysiology and alleviate symptoms, making it a prime candidate for AD drug discovery research. To date, most cannabis and AD research has focused on the major cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), paying little attention to other plant constituents with therapeutic properties for AD. This chapter will highlight emerging evidence on the therapeutic potential of medicinal cannabis going beyond CBD and THC to discuss cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabinoid acids, and other cannabinoid homologs, terpenes, and flavonoids that may have relevance to AD therapy. Further, the entourage effect, clinical implications, and directions for future research will be discussed.
... Interestingly, the EOs obtained from T3 were richer in β-caryophyllene, a sesquiterpene hydrocarbons believed to be a full agonist of the endocannabinoid CB2 receptor, also capable of exerting concerted action with CBD and THC (Russo and Marcu, 2017). On the other hand, an EO obtained from material collected at the end of the plant's life cycle could find application in plant defense, being caryophyllene oxide useful as broad-spectrum fungicide and insecticide (Russo and Marcu, 2017). ...
... Interestingly, the EOs obtained from T3 were richer in β-caryophyllene, a sesquiterpene hydrocarbons believed to be a full agonist of the endocannabinoid CB2 receptor, also capable of exerting concerted action with CBD and THC (Russo and Marcu, 2017). On the other hand, an EO obtained from material collected at the end of the plant's life cycle could find application in plant defense, being caryophyllene oxide useful as broad-spectrum fungicide and insecticide (Russo and Marcu, 2017). ...
... (E)-β-Famesene Application in neurodegenerative diseases As an alarm pheromone Russo and Marcu (2017) β-Elemene Anticancer, anti-inflammatory Jiang et al. (2017) The ethyl acetate extract from S. polydactyla, a polar compound, showed a noticeable inhibition zone against E. coli and P. aeruginosa. The work by Afifi et al. (2016) on the antimicrobial properties of S. polydactyla reported effective inhibitory activity in Gram-positive bacterial isolates (Bacillus sp. and S. aureus). ...
... Aromadendrene oxide 2 induces apoptosis in skin epidermoid cancer cells (Pavithra et al. 2018). (E)-β-Famesene has been studied for its application in neurodegenerative diseases as an alarm pheromone (Russo and Marcu 2017). Limonen-6-ol, pivalate has been reported to have antioxidant, anti-inflammatory, and insect-repellent activity . ...
Jahajeeah D, Bhoyroo V, Ranghoo-Sanmukhiya M. 2023. Antimicrobial properties and metabolite profiling of the ethyl acetate fractions of Sinularia polydactyla and Cespitularia simplex surrounding Mauritius Island. Indo Pac J Ocean Life 7: 133-142. Soft corals form an integral part of the reef ecosystem. This study assessed the antibacterial activities of Mauritius Island's soft cora ls and their different natural compounds having important biological properties. Antimicrobial assays and GCMS-MS analysis were performed using ethyl acetate extracts of Sinularia polydactyla and Cespitularia simplex. The results for both species indicated significant activity against most clinically pathogenic bacterial strains tested. In addition, S. polydactyla and C. simplex extracts gave the most potent action spectra yielding the largest inhibition zone diameter, especially against the Gram-positive Staphylococcus aureus (8.73 ± 2.87 and 6.00 ± 1.20 mm), respectively. The MIC also confirmed that the Gram-positive Bacillus subtilis and S. aureus strains were the most susceptible bacteria when exposed to the soft coral extracts, while Pseudomonas aeruginosa and Escherichia coli were the most resistant Gram-negative strains. The biochemical profile of the extracts showed the presence of terpenoids, steroids, flavonoids, coumarins, and quinones. GCMS-MS analysis also identified 151 compounds in S. polydactyla and 91 compounds in C. simplex. Several previously published studies have shown the biological activities of different species of Cespitularia; however, this is the first study to demonstrate the antibacterial activity and compound profiling of C. simplex. Although studies have been carried out on S. polydactyla extracts, compounds such as 25-Hydroxycholesterol and spathulenol have not yet been reported. The results from the study suggest that both S. polydactyla and C. simplex are potential sources of novel antibiotics and possess a myriad of chemical compounds which may lend themselves to bioprospecting.
... A Cannabis sativa, conhecida nas antigas sociedades agrícolas asiáticas, africanas e europeias devido ao seu efeito alucinógeno e terapêutico, contém compostos biológicos e quimicamente ativos conhecidos como canabinóide (Kisková et al., 2019, dentre estes os mais estudados até agora são: O delta-9-tetrahidrocanabinol (THC) e o canabidiol (CBD) (Russo & Marcu, 2017;Rahman et al, 2019). Sendo assim, substâncias estudadas, capazes de integrar esses cuidados. ...
... Vários estudos pré-clínicos demonstraram o potencial dos canabinóides contra vários tipos de câncer (leucemia, linfoma, glioblastoma, colorretal, pâncreas, colo do útero e próstata) e também do câncer de mama. A cannabis e seus constituintes podem modular várias vias relacionadas ao câncer, como PKB, AMPK, CAMKK-β, mTOR, PDHK, HIF-1α e PPAR-γ(Russo & Marcu, 2017).Outras explicações dos estudos recentes sobre o efeito dos CB's na cura do câncer de mama estava relacionado à combinação de terapia com canabidiol (CBD) com a terapia fotodinâmica (PDT) resultando na redução de efeitos colaterais e toxicidade para células normais, melhorando a qualidade de vida do paciente no tratamento do câncer de mama e, também para outros tipos de câncer. Essa terapêutica associada impedem a progressão e o desenvolvimento do câncer de mama, sendo necessário, porém, mais estudos das vias moleculares ligadas a ambas as terapias para melhorar a eficácia(Mokoena et al, 2019).Em concordancia com este achado, os estudiosos (Shekher at al., 2021) afirmam que os CBs podem bloquear o crescimento celular, a progressão do ciclo celular e induzir a apoptose seletivamente nas células tumorais, aumentando a eficácia da terapêutica contra o câncer, possibilitando a modulação.As células cancerígenas possuem a capacidade de adaptação às mudanças que ocorrem em seu microambiente e isso faz com que a monoterapia não possua eficácia máxima no tratamento. ...
Este estudo visou mapear o escopo das evidências científicas sobre os efeitos terapêuticos dos canabinóides no câncer de mama. Estudo metodológico de revisão de escopo da literatura científica nas bases: Scopus, PubMed e MEDline, sendo acessadas por meio do Portal de Periódico CAPES/MEC e nas bases: Science Direct, Cochrane e Biblioteca Virtual de Saúde. Após teste e reteste uttilizando o operador conectivo booleano AND, foram aplicados na nas bases de dados os seguintes descritores: (therapeutic uses cannabis) AND (therapy) AND (breast cancer or breast neoplasms). Os resultados encontrados apontaram six estudos, apenas um do tipo quantitativo e cinco de revisão de literatura que apresentaram uso terapêutico integrativo dos canabinóides e seus benefícios para o alivio dos sintomas. Concluiu-se que há escassez de evidências científicas sobre o alivio dos sintomas e das formas de uso da terapêutica integrativa das canabinóides no câncer de mama.
... Galbanum, a fragrant and resinous material derived from the root of this plant, consists of valuable chemicals with application in the production of fragrances, perfume, and biofuel [6], treatment of bladder and kidney stones [7], flavoring of foodstuffs and drinks, and production of antitumor, analgesic, and immune-boosting pharmaceutics and antifungal, anti-inflammatory compounds [8]. Hence, the extraction and fractionation of galbanum EO ingredients are required for producing such higher value-added products [9]. ...
Galbanum essential oil (EO) and its components have a wide industrial use based on constituents. In this regard, developing a feasible method for obtaining fractions containing different compositions with specific properties can be more beneficial than using the raw EO. Here, galbanum EO was extracted using hydrodistillation method which yielded 21.52%, containing α-pinene (3.26%), β-pinene (72.79%), β-myrcene (2.37%), α-phellandrene (0.87%), copaene (0.92%), and azulene (0.85%) detected using GC-MS and GC-FID. The influence of three operational parameters including distillation periods, reflux ratio, and reboiler heat on the purity of the resultant fractions was explored. Firstly, time-dependent fractional distillation of the extracted EO was conducted and fractions with different contents of each component were collected. The maximum mass fractions of aforementioned components were 9.18%, 89.12%, 3.14%, 1.18%, 1.45%, and 2.73% (wt.%), respectively. Secondly, utilization of the reflux ratio (5:1) had no substantial effect on the purity of the components whereas it resulted in additional time and energy consumption. Finally, decreasing the heat of the reboiler to 75% of its baseline value and subsequently enhancing the contact time of the phases along the column significantly boosted the purity of α-pinene and β-pinene, achieving 24.52% (wt.%) and 92.38% (wt.%), respectively. There was no evidence of thermal degradation in any of the experiments, notwithstanding considerable thermal sensitivity of the EO. These findings indicate that fractional distillation can be an effective approach in achieving fractions that are richer in desired components in galbanum EO.
... While the side effects of MC are mainly non-severe Ware et al. 2015), its efficacy is disputed and mechanisms of action lack clarity (Fisher et al. 2021;Häuser et al. 2018). These unclarities could stem from many reasons, including the great variety of cannabis based medical products and variants of cannabis plants (Russo & Marcu 2017;Schlag et al. 2021), as well as the complexity of the molecular targets of different cannabinoids (Mlost et al. 2020;Morales et al. 2017). Another possible reason for the inconsistencies in previous research is the complex effects of cannabis on the psyche, which is our focus in the present study. ...
Background
Medical cannabis (MC) is increasingly used for chronic pain, but it is unclear how it aids in pain management. Previous literature suggests that MC could holistically alter the pain experience instead of only targeting pain intensity. However, this hypothesis has not been previously systematically tested.
Method
A retrospective internet survey was used in a sample of Finnish chronic pain patients (40 MC users and 161 opioid users). The patients evaluated statements describing positive and negative phenomenological effects of the medicine. The two groups were propensity score matched to control for possible confounding factors.
Results
Exploratory factor analysis revealed three experience factors: Negative Side Effects, Positive Holistic Effects, and Positive Emotional Effects. The MC group (matched n = 39) received higher scores than the opioid group (matched n = 39) in Positive Emotional Effects with large effect size (Rank-Biserial Correlation RBC = .71, p < .001), and in Holistic Positive Effects with medium effect size (RBC = .47, p < .001), with no difference in Negative Side Effects ( p = .13). MC and opioids were perceived as equally efficacious in reducing pain intensity. Ratings of individual statements were exploratively examined in a post hoc analysis.
Conclusion
MC and opioids were perceived to be equally efficacious in reducing pain intensity, but MC additionally positively affected broader pain-related factors such as emotion, functionality, and overall sense of wellbeing. This supports the hypothesis that MC alleviates pain through holistically altering the pain experience.
... Terpinolene is a monocyclic monoterpene most commonly found in Citrus [61] and pine (Pinus) [62]. While there is a lack of sufficient evidence of terpinolene's anxiolytic effect or mechanism of action, previous studies have demonstrated terpinolene's pharmacological properties to include sedative [61], antifungal, and antioxidant activity [63]. ...
Terpenes are the most extensive and varied group of naturally occurring compounds mostly found in plants,
including cannabis, and have an array of potential therapeutic benefits for pathological conditions. The endocannabinoid system can potently modulate anxiety in humans, rodents, and zebrafish. The ‘entourage effect’
suggests terpenes may target cannabinoid CB1 and CB2 receptors, among others, but this requires further
investigation. In this study we first tested for anxiety-altering effects of the predominant ‘Super-Class’ terpenes,
bisabolol (0.001%, 0.0015%, and 0.002%) and terpinolene (TPL; 0.01%, 0.05%, and 0.1%), in zebrafish with the
open field test. Bisabolol did not have an effect on zebrafish behaviour or locomotion. However, TPL caused a
significant increase in time spent in the inner zone and decrease in time spent in the outer zone of the arena
indicating an anxiolytic (anxiety decreasing) effect. Next, we assessed whether CB1 and CB2 receptor antagonists,
rimonabant and AM630 (6-Iodopravadoline) respectively, could eliminate or reduce the anxiolytic effects of TPL
(0.1%) and β-caryophyllene (BCP; 4%), another super-class terpene previously shown to be anxiolytic in
zebrafish. Rimonabant and AM630 were administered prior to terpene exposure and compared to controls and
fish exposed to only the terpenes. AM630, but not rimonabant, eliminated the anxiolytic effects of both BCP and
TPL. AM630 modulated locomotion on its own, which was potentiated by terpenes. These findings suggest the
behavioural effects of TPL and BCP on zebrafish anxiety-like behaviour are mediated by a selective preference for
CB2 receptor sites. Furthermore, the CB2 pathways mediating the anxiolytic response are likely different from
those altering locomotion.
... Only a small proportion of this consists of cannflavins. 44 The distributions of flavonoids and cannabinoids in cannabis tissues are different, and there is no indication that the trichomes are involved in the biosynthesis of flavonoids. 45 In addition to tissue-specific distribution, flavonoid profiles were also shown to vary over time during plant maturation. ...
Background: Throughout history, Cannabis has had a significant influence on human life as one of the earliest plants cultivated by humans. The plant was a source of fibers used by the oldest known civilizations. Cannabis was also used medicinally in China, India, and ancient Egypt. Delta-9-tetrahydrocannabinol (Δ9-THC), the main psychoactive compound in the plant was identified in 1964 followed by more than 125 cannabinoids. More than 30 flavonoids were isolated from the plant including the characteristic flavonoids called cannflavins, which are prenylated or geranylated flavones.
Material and Methods: In this review, the methods of extraction, isolation, identification, biosynthesis, chemical synthesis, analysis and pharmacological activity of these flavonoids are described.
Results: The biosynthetic routes of the cannflavins from phenylalanine and malonyl CoA as well as the microbial biotransformation are also discussed. Details of the chemical synthesis are illustrated as an alternative to the isolation from the plant materials along with other possible sources of obtaining cannflavins. Detailed methods discussing the analysis of flavonoids in cannabis are presented, including the techniques used for separation and detection. Finally, the various biological activities of cannflavins are reviewed along with the available molecular docking studies.
Conclusion: Despite the low level of cannflavins in cannabis hamper their development as naturally derived products. Efforts need to be put in place to develop high yield synthetic or biosynthetic protocols for their production in order for their development as pharmaceutical products.
... Cannabidiol (CBD) is a phytocannabinoid extracted from cannabis plant species, including Cannabis indica, Cannabis sativa, or Cannabis ruderalis (also commonly known as hemp or marijuana) [1]. Although structurally similar to the psychoactive cannabinoid delta-9-tetrahydrocannabinol (THC), CBD does not cause intoxication or euphoric states and thus has low abuse potential while exhibiting a wide range of pharmacological effects [2]. A number of studies and clinical trials are now emerging that show CBD exhibits various therapeutic effects in conditions that range from epilepsy, psychotic disorders, anxiety, diabetes, sleep disorders, cardiovascular diseases, rheumatoid arthritis, pain, skin aging, antioxidant, and inflammation to cancer therapy [3][4][5]. ...
Cannabidiol (CBD), derived from the cannabis plant, has gained significant attention due to its potential therapeutic benefits. However, one of the challenges associated with CBD administration is its low bioavailability, which refers to the fraction of an administered dose that reaches systemic circulation. This limitation necessitates the exploration of various approaches to enhance the bioavailability of CBD, thus helping to maximize its therapeutic potential. A variety of approaches are now emerging, including nanoemulsion-based systems, lipid-based formulations, prodrugs, nanocarriers, and alternative routes of administration, which hold promise for improving the bioavailability of CBD and pave the way for novel formulations that maximize the therapeutic potential of CBD in various medical conditions. This opinion piece presents the current understanding surrounding CBD bioavailability and considers strategies aimed at improving both its absorption and its bioavailability.
... Enquanto isso, o CBD é descrito como modulador alostérico negativo (Russo & Marcu 2017), reduzindo os efeitos potencialmente tóxicos do THC (Laprairie et al, 2015;Thakur et al., 2005). ...
A busca por tratamentos alternativos e distintas utilidades clínicas da cannabis medicinal apresenta crescimento importante nos últimos anos. Nesse contexto, este estudo tem como objetivo avaliar o uso de cannabis medicinal como tratamento para os transtornos por uso de opioides. Por meio de uma análise sistemática, utilizando as bases de dados PubMed e Medline, foi realizado uma busca, dando preferência a ensaio clínicos, meta-análises e revisões bibliográficas dos últimos 10 anos, em animais e humanos utilizando os termos “cannabis”, “opioids”, “addiction” e “treatment”. Foram excluídos artigos com os termos “smoker”, “smoking” e “pregnant" no título ou resumo, também foram excluídos estudos em andamento. Observou-se redução dos sintomas de crise de abstinência, com efeito prolongado e bom perfil de segurança. Os estudos mostram resultados preliminares positivos, no entanto, contam com amostras reduzidas, sem padronização dos canabinóides sintéticos e suas respectivas posologias. Por isso, são necessários estudos com padronização de parâmetros e maior número de amostra para conclusões assertivas.
... Moreover, the parasitoid Aphidius gifuensis Ashmead, 1906 showed a preference for treated plants and, in terms of olfaction and landings, performed more successfully on treated plants than on healthy plants [43]. Ocimene is a monoterpene found in nature, and (E)β-ocimene is known to exhibit anticonvulsant, antifungal, antitumor, and pest-resistant properties [75]. Medical cannabis has a high ocimene content. ...
Simple Summary
Cassava (Manihot esculenta Crantz; Euphorbiaceae) plants have a long lifecycle. They remain in the field for at least 10 months and are exposed to numerous pests. Seventeen groups of pests that affect this crop have been identified. These include 35 species found in the Americas, 11 in Africa, and 6 in Asia, totalling approximately 200 arthropod species that feed on cassava. Whiteflies are considered one of the main pests of cassava worldwide. In northeastern Brazil, the most common whitefly species causing severe damage to cassava is Aleurothrixus aepim (Goeldi, 1886) (Hemiptera: Aleyrodidae). Cassava plants emit volatile organic compounds and secrete extrafloral nectar; these substances may be essential for developing biological control strategies against pests. Herein, we describe variations in the blend constitution and individual concentrations of constitutive volatile organic compounds released by two cassava genotypes. Additionally, we highlight the activity of a monoterpene, considering that the resistant genotype emitted higher concentrations of this compound.
Abstract
Cassava is an essential tuber crop used to produce food, feed, and beverages. Whitefly pests, including Aleurothrixus aepim (Goeldi, 1886) (Hemiptera: Aleyrodidae), significantly affect cassava-based agroecosystems. Plant odours have been described as potential pest management tools, and the cassava clone M Ecuador 72 has been used by breeders as an essential source of resistance. In this study, we analysed and compared the volatile compounds released by this resistant clone and a susceptible genotype, BRS Jari. Constitutive odours were collected from young plants and analysed using gas chromatography–mass spectrometry combined with chemometric tools. The resistant genotype released numerous compounds with previously described biological activity and substantial amounts of the monoterpene (E)-β-ocimene. Whiteflies showed non-preferential behaviour when exposed to volatiles from the resistant genotype but not the susceptible genotype. Furthermore, pure ocimene caused non-preferential behaviour in whiteflies, indicating a role for this compound in repellence. This report provides an example of the intraspecific variation in odour emissions from cassava plants alongside information on odorants that repel whiteflies; these data can be used to devise whitefly management strategies. A better understanding of the genetic variability in cassava odour constituents and emissions under field conditions may accelerate the development of more resistant cassava varieties.
... However, due to the lack of selectivity of these processes and similar physico-chemical properties of cannabinoids, the new products might not only be rich in non-intoxicating cannabinoids but might also contain THC levels above those regulated. THC-rich products can still be commercialized, but producers and consumers must acquire legal permits from official agencies (Russo and Marcu, 2017). Thus, there is a serious demand for finding new strategies to allow the THC-remediation of hemp extracts, i. e., simultaneous enhancement in non-intoxicating cannabinoids and total/partial removal of THC, and generate so-called 'full spectrum' formulas. ...
The presence of tetrahydrocannabinol (THC) in cannabinoid-based materials, such as hemp flower extracts, can pose a severe commercialization burden. In this study, various operating modes of liquid–liquid chromatography (LLC), i.e., batch mode (conventional), trapping multiple dual mode (semi-continuous), and sequential mode (continuous), were evaluated for the THC-remediation of hemp extracts. The biphasic system composition, the feed concentration range, and the maximum flow rate were selected in preliminary experiments. The operating parameters were chosen using short-cut methods, whereas simulations were based on the equilibrium-cell model. Batch elution provided good productivity, easy operation, and yielded a THC-free hemp extract. Trapping multiple dual mode showed a lower productivity than batch, whereas the sequential mode afforded a THC-free
extract with a similar composition to the batch mode and offered the advantage of continuous operation and superior productivity. The results of this work constitute a solid basis for the model-based design and optimization of LLC processes for the industrial remediation of hemp extracts.
... One of the main effects is the anticonvulsant effect of cannabinoids, especially in CBD and THC. 73 A seizure is a sudden change in the human brain that cannot be controlled, leading to symptoms such as confusion, fear, anxiety, muscle twitching, and unconsciousness. THC may decrease the effect of these seizures by being an agonist of the CB1 receptor and acting directly on the brain. ...
Scientific evidence exists about the association between neurological diseases (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, depression, and memory loss) and oxidative damage. The increasing worldwide incidence of such diseases is attracting the attention of researchers to find palliative medications to reduce the symptoms and promote quality of life, in particular, in developing countries, e.g., South America and Africa. Among potential alternatives, extracts of Cannabis Sativa L. are suitable for people who have neurological disorders, spasticity, and pain, nausea, resulting from diseases such as cancer and arthritis. In this review, we discuss the latest developments in the use of Cannabis, its subtypes and constituents, extraction methods, and relevant pharmacological
effects. Biomedical applications, marketed products, and prospects for the worldwide use of Cannabis
Sativa L. extracts are also discussed, providing the bibliometric maps of scientific literature published in representative countries from South America (i.e., Brazil) and Africa (i.e., South Africa). A lack of evidence on the effectiveness and safety of Cannabis, besides the concerns about addiction and other adverse events, has led many countries to act with caution before changing Cannabis-related regulations. Recent findings are expected to increase the social acceptance of Cannabis, while new technologies seem to boost the global cannabis market because the benefits of (-)-trans-delta-9-tetrahydrocannabinol (delta9-THC) and cannabidiol (CBD) use have been proven in several studies in addition to the potential to general new employment.
... In our study, the primary compounds identified in the essential oil of P orientalis L. were α and γ eudesmol isomers, which are bicyclic sesquiterpenoid alkene alcohols (Russo and Marcu, 2017). In HepG2 cells, α-eudesmol was found to have cytotoxic effects at low concentrations in the range of micrograms per millilitre. ...
ABSTRACT
Introduction: Platanus orientalis L, a traditional medicine, is used to alleviate symptoms of allergic rhinitis (AR) in
patients. This study aimed to evaluate the efficacy and safety of P orientalis L. distillate in treating AR patients.
Methods: This double-blinded, placebo-controlled pilot clinical trial study included 30 AR patients who received
either P orientalis L. distillate or placebo nasal drops for four weeks. Patients' symptoms, physician's assessment,
quality of life, and adverse effects were evaluated. Gas chromatography–mass spectrometry (GC-MS) was used to
analyse the chemical composition of the distillate.
Results: P orientalis L. distillate significantly relieved nasal symptoms (P < 0.05) and improved all domains of
quality of life (P < 0.05) compared to the baseline level. However, a similar effect was observed in the placebo
group. No serious adverse events were reported.
Conclusions: P orientalis L. distillate is safe and effective in treating nasal symptoms and improving the quality of
life in AR patients. However, the placebo effect cannot be ignored.
... Recovery from PTSD is correlated to reducing these levels, irrespective of treatment modality or outcome. [60,61] This correlation indicates that the intromission of anti-inflammatory phytochemicals may help modulate the chronic inflammatory state of PTSD, as quantified by concentrations of inflammatory cytokines. [62] The phytocannabinoids CBD, CBG, CBN, and CBC have been individually identified as antiinflammatory agents, and the entourage of these molecules enhanced the phytocannabinoid-mediated pro and antiinflammatory cytokine responses in preclinical in vivo studies. ...
This literature review examines theoretical frameworks related to applying the principles of biomolecular psychology and psychoneuroimmunology to devise a nutraceutical protocol utilizing phytochemicals for the treatment of posttraumatic stress disorder with a particular focus on modulating the endocannabinoid system through the utilization of molecules inherent in chemovars of Cannabis sativa. It provides a psychosocial overview of posttraumatic stress disorder and the historically controversial and noncontroversial nature of the biologically derived molecules that have demonstrated efficacy in addressing the effects major stressors have on the biomolecular mechanisms that cause mood disorders that manifest themselves as symptoms of PTSD.
... Caryophyllene oxide is a sesquiterpenoid oxide found in lemon balm, eucalyptus, prickly paperbark [37], with a wide-spectrum antifungal activity in plant defense and insecticidal/antifeedant properties [38,39]. Antifungal, antibacterial, and antiplatelet aggregation activities of caryophyllene oxide have also been proven [40,41]. It is believed that caryophyllene oxide contributes to the potent cytotoxic effects observed in the essential oil of Heteropyxis dehniae leaves [42]. ...
Bioactive plant compounds, also known as phytochemicals, are essential for plant resistance, growth, and development. These chemicals often possess therapeutic properties that have been used in traditional medicine for centuries as herbal remedies for a variety of diseases. As a member of the Lamiaceae family, Rydingia (Syn: Otostegia) is found in Asia and northeastern Africa. R. michauxii, is a unique shrub that grows in the Southern region of Iran, Fars province. Rydingia species have been used as traditional herbal medicine in Iran for many years. It seems that R. michauxii offers great potential for in-depth research on its diverse biological properties, especially its antioxidant and lipid-lowering effects. Nevertheless, no clinical investigation has been carried out on the phytochemical characteristics of this plant to date. Therefore, this study aims to contribute to the scientific knowledge on the pharmacological properties of R. michauxii and its phytochemical compounds and encourage researchers to evaluate its biological properties in animal models. In this study, all available scientific literature was compiled and all phytochemical and pharmacological properties of the R. michauxii plant were investigated, including antibacterial, antifungal, antiviral, antioxidant, antimalarial, cytotoxic, and lipid-lowering effects, which may prove useful in developing novel formulations with greater therapeutic benefits in clinical applications.
... CBN, unlike CBD and CBG, has weak psychoactive properties (about 10 times weaker than Δ9-THC), yet many countries allow its usage in sleep aiding remedies due to its sedative effect on humans. Its anticonvulsant, anti-inflammatory, antibiotic, and anti-MRSA (methicillin-resistant Staphylococcus aureus) properties are also well known [5]. ...
The sensitivity of complex analytical procedures depends not only on the sensitivity of the analytical instrument used, but also on the recovery degree of the examined analyte by the employed sample preparation method. The recovery degrees of individual cannabinoids reported in literature, estimated using the same sample preparation method, are unexpectedly divergent. Therefore, the aim of this study was a thorough assessment of the most commonly used sample preparation methods, such as protein precipitation, LLE, QuEChERS and SPE, in the context of the reliability of the obtained results. The presented report shows that the highest sensitivity, precision and reliability of the chromatographic analysis of CBG, CBD, ∆9-THC and CBN in human plasma can be obtained using SPE. The recovery degrees of these cannabinoids by SPE are highly repeatable and exceed 95 %, while they are significantly lower for such sample preparation methods as protein precipitation, LLE and QuEChERS (ca. 80, 65 and 87, respectively). Moreover, the supernatants obtained by the latter methods contain interferents evoking matrix-effect, which makes reliable quantification of the listed cannabinoids by GC difficult. To our knowledge, the paper is the first such extensive comparison of sample preparation procedures used for the determination of cannabinoids in plasma by GC-MS and HPLC-MS. The presented results and the discussion allow to understand why different recovery degrees for the same xenobiotic can be find in literature despite they have been estimated using the same or different sample preparation method or different chromatography types.
... Cannabis flowers and leaves have a distinctive aroma, and the plant's extracts include a variety of beneficial flavonoids, terpenes, and other compounds that are efficient insecticides, fungicides, and therapeutic agents (Pellati et al., 2018). The flower, leaves, oil, and trichome of the plant have been shown to be cytotoxic, antimicrobial, antioxidant, antihypertensive, antipyretic, and appetite-stimulating (Russo and Marcu, 2017). The flower extracts with antioxidant activity have been shown to have health-promoting and anti-aging properties, and are utilized to treat a variety of metabolic and chronic disorders, including glaucoma, pain, depression, cancer, liver disease, cardiovascular diseases, inflammation, and metabolic syndrome (Nallathambi et al., 2017). ...
Cannabis sativa , also known as “hemp” or “weed,” is a versatile plant with various uses in medicine, agriculture, food, and cosmetics. This review attempts to evaluate the available literature on the ecology, chemical composition, phytochemistry, pharmacology, traditional uses, industrial uses, and toxicology of Cannabis sativa . So far, 566 chemical compounds have been isolated from Cannabis , including 125 cannabinoids and 198 non-cannabinoids. The psychoactive and physiologically active part of the plant is a cannabinoid, mostly found in the flowers, but also present in smaller amounts in the leaves, stems, and seeds. Of all phytochemicals, terpenes form the largest composition in the plant. Pharmacological evidence reveals that the plants contain cannabinoids which exhibit potential as antioxidants, antibacterial agents, anticancer agents, and anti-inflammatory agents. Furthermore, the compounds in the plants have reported applications in the food and cosmetic industries. Significantly, Cannabis cultivation has a minimal negative impact on the environment in terms of cultivation. Most of the studies focused on the chemical make-up, phytochemistry, and pharmacological effects, but not much is known about the toxic effects. Overall, the Cannabis plant has enormous potential for biological and industrial uses, as well as traditional and other medicinal uses. However, further research is necessary to fully understand and explore the uses and beneficial properties of Cannabis sativa .
... Within several weeks growth from predominantly the inflorescence's clustered calyces synthesis of white hair-like glandular trichomes (Fig. 1), C. sativa can organically produce 5 L per hectare of terpene-rich essential oil (Marco et al., 2019). Among the 545 identified compounds in C. sativa, 200 terpenes have been identified, including monoterpenes, sesquiterpenes, and triterpenes (Russo & Marcu, 2017). These highly concentrated aromatic compounds contribute to the C. sativa plant's reproductive success, antimicrobial activities, and herbivore deterrence (Buchbauer & Ilic, 2013). ...
... The plant also exhibited preclinical antioxidative, antihypertensive, antiinflammatory, antidiabetic, antineuroinflammatory, antiarthritic, antiacne, and antimicrobial activities as well as estrogenic and renal protective properties (Lim et al., 2021), thanks to the contribution of the C. sativa derived biometabolites, e.g., cannabinoids, terpenoids, alkaloids, and flavonoids, for exhibiting diverse pharmacological properties (Russo & Marcu, 2017). Numerous clinical trials need to be performed globally to corroborate the biotherapeutic benefits of traditionally used C. sativa as well as to establish safe phytotherapeutic guidelines in the future. ...
Conceivably, one of the oldest and most controversial plants ever discovered by humans was Cannabis sativa Linnaeus that has been exploited for therapeutic, recreational, and religious purposes as well as source of fibers, oil, and food for millennia. This chapter has accumulated the uses of C. sativa as a traditional phytotherapeutic, reported from the different geographical locations. This chapter encloses different countries that have traditionally used C. sativa to treat and prevent arthritis, diabetes, pain, cancer, rheumatism, digestive problems, gastrointestinal disorders, gynecological disorders, nervous disorders, piles, respiratory complications, tuberculosis, sexual disorders, sleep disorders, sexually transmitted diseases, skin disorders, urinary disorders, and so on, thanks to the contribution of the cannabinoids and other bioactive compounds to the diverse biological properties. Innumerable clinical trials need to be performed rigorously to form safe phytopharmaceutical guidelines for utilizing the medicinal benefits of a wonder plant, C. sativa.
... Some research also suggests that visual and olfactory inspection can provide valuable information about the potential effects of a particular strain. For example, terpenes, which provide the characteristic smell of cannabis and vary by type and amount across different strains, may be partially responsible for different physiological and cognitive effects (Blasco-Benito et al. 2018;LaVigne et al., 2021, Lewis et al. 2018Russo & Marcu 2017;Sawler et al. 2015). Furthermore, the ability to inspect and select strains and dosages reflects a higher level of autonomy, and previous research has found that individuals who accessed illegal sources of medical cannabis value autonomy in their healthcare decisions (Bottorff et al. 2011;Fainzang 2013;Hanna & Hughes 2011). ...
Background
Throughout the past two decades of legal medical cannabis in Canada, individuals have experienced challenges related to accessing legal sources of cannabis for medical purposes. The objective of our study was to examine the sources of cannabis accessed by individuals authorized to use medical cannabis and to identify possible reasons for their use of illegal sources.
Methods
Individuals who participated in the Cannabis Access Regulations Study (CANARY), a national cross-sectional survey launched in 2014, and indicated they were currently authorized to use cannabis for medical purposes in Canada were included in this study. We assessed differences between participants accessing cannabis from only legal sources versus from illegal sources in relation to sociodemographic characteristics, health-related factors, and characteristics of medical cannabis they considered important. A secondary analysis assessed differences in satisfaction with various dimensions of cannabis products and services provided by legal versus illegal sources.
Results
Half of the 237 study participants accessed cannabis from illegal sources. Individuals accessing cannabis from illegal sources were significantly more likely to value pesticide-free products, access to a variety of strains, ability to select strain and dosage, ability to observe and smell cannabis, availability in a dispensary, and availability in small quantities than did individuals accessing cannabis from only legal sources (all p < 0.05). Additionally, participants gave significantly higher satisfaction scores to illegal sources than to legal sources on service-related dimensions of cannabis access (all p < 0.05).
Conclusion
Our findings contribute to an understanding of reasonable access to medical cannabis from a patient perspective and how to assess whether it has been achieved. Characteristics of cannabis products and services valued by patients and appropriate to their needs should be incorporated into legal medical cannabis programs to promote the use of legal medical sources. While pertaining specifically to medical use of cannabis in Canada, the findings of this study may also be instructive for understanding the use of illegal cannabis sources for non-medical purposes in Canada and provide insight for other jurisdictions implementing cannabis regulations for both medical and non-medical purposes.
... The majority of the fatty acids in hempseed oil represent linoleic acid, oleic acid, stearic acid and palmitic acid (Bielecka et al., 2014). They are known to contain omega-3 and omega-6 (linoleic and linolenic acids) in a 3:1 ratio (Vonapartis et al., 2015) but they do not contain any cannabinoids or terpenoids (Russo and Marcu, 2017). This is of importance due to the risk of exceeding the permitted limit of cannabinoids. ...
One of the main breeding objectives for hemp (Cannabis sativa L.) cultivation is higher seed yield important also
for the oil yields. However, there has been limited research on hemp breeding that focuses on these topical
features. In this study, 17 crosses were created using 12 different hemp varieties. For each variety, five female
inflorescences were selected for targeted crossing and one for self-pollination. Seeds from the crosses were sown
in separate plots with a seeding density of 30 kg/ha. The number of male and female plants, plant height,
internode length, steam thickness, inflorescence length, number of inflorescences per plant, and plant number
per plot were measured in crossbred family plants. The absolute weight of seeds per plot, the degree of marbling
and oil content were determined. The progeny of the cross between Helena and Tiborszallasi were found to have
the highest 100 seed mass (1.546 g, upper half). The offspring of self-pollinated varieties Finola, Tiborszallasi,
Fedora 17 and the cross between Helena and Tiborszallasi produced the highest oil content. The progeny of the
cross between Futura 75 and KC Dora showed the most promising results in terms of high yield production. This
study provided the first important data pertaining to hemp breeding with the goal of increasing oil content and
seed yield.
... They are responsible for the characteristic smell and flavoring of the plant and derivates [39]. Among them, α-pinene, terpinene, caryophyllene, limonene, and myrcene are the most recurrent compounds in PlL EO of leaves [17,[40][41][42][43]. Additionally, up to 64 fractions have been identified in the leaves EO fingerprint, among which some terpenoids are constituent fractions of Cannabis sativa [44] and are reported as "non-cannabinoid terpenoids." They can induce cannabinoid-like properties in immunemediated inflammatory and autoimmunity diseases, neuroinflammatory, neurological, and neurodegenerative conditions, and exert anti-infective and anti-cancer properties [45,46]. ...
Pistacia lentiscus L. (PlL) has been used for centuries in traditional medicine. The richness in antimicrobial biomolecules of Pll derivates can represent an alternative to chemically formulated agents used against oral infections. This review summarizes the knowledge on the antimicrobial activity of PlL essential oil (EO), extracts, and mastic resin against microorganisms being of relevance in oral biofilm-associated diseases. Results demonstrated that the potential of PlL polyphenol extracts has led to increasing scientific interest. In fact, the extracts are a significantly more effective agent than the other PlL derivates. The positive findings regarding the inhibition of periodontal pathogens and C. albicans, together with the antioxidant activity and the reduction of the inflammatory responses, suggest the use of the extracts in the prevention and/or reversal of intraoral dysbiosis. Toothpaste, mouthwashes, and local delivery devices could be effective in the clinical management of these oral diseases.
... Indeed, the application of both OEG and OEGCM is promising in preclinical studies not only in regeneration (Shyu et al., 2008;Myers et al., 2016) but also in cancer therapy (Carvalho et al., 2018). In addition to the unprecedented finding of CB1 involvement in OEGCM effects, our study suggests that OEGs could be a therapeutic target for endo-and phytocannabinoids (Russo and Marcu, 2017), with a focus on CB1 and MAGL. In addition, the ECS might regulate the composition of trophic activity present in OEGCM, as well as its ability to increase the branching complexity of OLs in hippocampal cell culture. ...
The endocannabinoid system (ECS) refers to a complex cell-signaling system highly conserved among species formed by numerous receptors, lipid mediators (endocannabinoids) and synthetic and degradative enzymes. It is widely distributed throughout the body including the CNS, where it participates in synaptic signaling, plasticity and neurodevelopment. Besides, the olfactory ensheathing glia (OEG) present in the olfactory system is also known to play an important role in the promotion of axonal growth and/or myelination. Therefore, both OEG and the ECS promote neurogenesis and oligodendrogenesis in the CNS. Here, we investigated if the ECS is expressed in cultured OEG, by assessing the main markers of the ECS through immunofluorescence, western blotting and qRT-PCR and quantifying the content of endocannabinoids in the conditioned medium of these cells. After that, we investigated whether the production and release of endocannabinoids regulate the differentiation of oligodendrocytes co-cultured with hippocampal neurons, through Sholl analysis in oligodendrocytes expressing O4 and MBP markers. Additionally, we evaluated through western blotting the modulation of downstream pathways such as PI3K/Akt/mTOR and ERK/MAPK, being known to be involved in the proliferation and differentiation of oligodendrocytes and activated by CB1, which is the major endocannabinoid responsive receptor in the brain. Our data show that OEG expresses key genes of the ECS, including the CB1 receptor, FAAH and MAGL. Besides, we were able to identify AEA, 2-AG and AEA related mediators palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in the conditioned medium of OEG cultures. These cultures were also treated with URB597 10-9 M, a FAAH selective inhibitor, or JZL184 10-9 M, a MAGL selective inhibitor, which led to the increase in the concentrations of OEA and 2-AG in the conditioned medium. Moreover, we found that the addition of OEG conditioned medium (OEGCM) enhanced the complexity of oligodendrocyte process branching in hippocampal mixed cell cultures and that this effect was inhibited by AM251 10-6 M, a CB1 receptor antagonist. However, treatment with the conditioned medium enriched with OEA or 2-AG did not alter the process branching complexity of premyelinating oligodendrocytes, while decreased the branching complexity in mature oligodendrocytes. We also observed no change in the phosphorylation of Akt and ERK 44/42 in any of the conditions used. In conclusion, our data show that the ECS modulates the number and maturation of oligodendrocytes in hippocampal mixed cell cultures.
... [12] As per some study it reduces colon adenoma in rats. [13] ...
... Most European countries allow the cultivation of hemp containing the upper legal limit of 0.2% THC for fiber and seed production (Petrović et al., 2015;Russo & Marcu, 2017). For these reasons, it has been a forbidden plant to be grown, kept and used in most countries. ...
In addition to being the oldest cultivated plant from past to present as a raw material source, Cannabis sativa L. is a strategically characteristic plant used for food, medicine, cosmetics, and pharmacological purposes. Molecular modeling is an important means for elucidating molecular structures and plays an important role in the design and development of new pharmaceuticals. This chapter includes the beneficial properties of the primary and secondary metabolites contained in cannabis such as foaming, emulsifying, gelling, film formation; antioxidant, antimicrobial activities and bakery products by means of their superior nutritional values, snack products, dairy products, processed meat products, in beverages such as coffees, teas, soda and functional food ingredients in many other areas of the food industry, nutritional supplements, usability in the development of new food formulations on hemp and molecular modeling studies on constituents of cannabis sativa.
... In addition, it showed anticancer activity in hepatocellular carcinoma by inducing mitochondrial apoptosis and promoting caspase 3 activation and PARP cleavage [38]. It also reduced the growth of MCF-7 cancer cells alone and in combination with paclitaxel [39]. ...
The aim of this study was to investigate the chemical profile and the cytotoxic activity in two castration-resistant prostate cancer (CRPC) cell lines of the leaf essential oil in Myrtus communis subsp. tarentina (L.) Nyman (EO MT), which was cultivated at the Ghirardi Botanical Garden (Toscolano Maderno, Brescia, Italy). The leaves were air-dried and extracted by hydrodistillation with a Clevenger-type apparatus, and the EO profile was characterized by GC/MS. For the cytotoxic activity investigation, we analyzed the cell viability by MTT assay, and the apoptosis induction by Annexin V/propidium iodide assay/Western blot analysis of cleaved caspase 3 and cleaved PARP proteins. Moreover, the cellular migration was analyzed by Boyden’s chamber assay and the distribution of actin cytoskeleton filaments by immunofluorescence. We identified 29 total compounds; the main compound classes were oxygenated monoterpenes, monoterpene hydrocarbons, and sesquiterpenes. The main constituents were α-pinene, α-humulene, α-terpineol, durohydroquinon, linalool, geranyl acetate, and β-caryophyllene. We found that EO MT was able to reduce cellular viability, activating an apoptotic process, and to decrease the migratory capacity of CRPC cells. These results suggest that it might be interesting to further investigate the effects of single compounds present in EO MT for their possible use in prostate cancer treatment.
... Among terpenes, myrcene (Figure 1), limonene, transocimene, and terpinolene are the most represented monoterpenes in the plant, while caryophyllene ( Figure 1) and humulene are the most abundant sesquiterpenes [7,10]. Cannabis-based treatments represent a promising opportunity, as indications suggest a synergistic effect between cannabinoids and terpenes that is superior to synthetic drugs, known as the "entourage effect" [13][14][15][16][17]. ...
The reproducibility of an extemporaneous preparation is an essential condition for guaranteeing the quality, efficacy, and safety of the medicinal product. This study aimed to develop a controlled one-step process for cannabis olive oil preparations by applying digital technologies. For this purpose, the chemical profile of cannabinoid contents in oil extracts of Bedrocan, FM2, and Pedanios varieties obtained with the already in use method, proposed by the Italian Society of Compounding Pharmacists (SIFAP), was compared with two new methods, specifically the Tolotto Gear® extraction method (TGE) and the Tolotto Gear® extraction method preceded by a pre-extraction procedure (TGE-PE). HPLC analyses showed that the concentration of THC using cannabis flos with a high THC content (over 20% w/w) was always higher than 21 mg/mL for the Bedrocan variety and close to 20 mg/mL for the Pedanios variety when applying TGE, while with TGE-PE, the THC concentration was higher than 23 mg/mL for the Bedrocan variety. For the FM2 variety, the amounts of THC and CBD in the oil formulations obtained using TGE were higher than 7 mg/mL and 10 mg/mL, respectively, and for TGE-PE, the concentrations of THC and CBD were higher than 7 mg/mL and 12 mg/mL, respectively. GC-MS analyses were performed to define the terpene contents in the oil extracts. The samples of Bedrocan flos extracted with TGE-PE displayed a distinctive profile, highly rich in terpenes and devoid of oxidized volatile products. Thus, TGE and TGE-PE allowed performing a quantitative extraction of cannabinoids and increasing the total mono-di-tri terpenes and sesquiterpene concentrations. The methods were repeatable and applicable to any quantity of raw material, preserving the phytocomplex of the plant.
... CBGA, in turn, is formed via olivetolic acid cyclase from olivetolic acid and geranyl pyrophosphate. Other less abundant OPEN therapeutically beneficial cannabinoids include C 5 -alkyl cannabichromenic acid (CBCA) and cannabinolic acid (CBNA) [21][22][23] . It was recently demonstrated that the bioactivity of cannabinoids on the human endocannabinoid system (ECS) is modulated by differences in alkyl chain length 24 , affecting the binding affinity of cannabinoids to respective ECS receptors. ...
C. sativa has gained renewed interest as a cash crop for food, fibre and medicinal markets. Irrespective of the final product, rigorous quantitative testing for cannabinoids, the regulated biologically active constituents of C. sativa, is a legal prerequisite across the supply chains. Currently, the medicinal cannabis and industrial hemp industries depend on costly chromatographic analysis for cannabinoid quantification, limiting production, research and development. Combined with chemometrics, Near-InfraRed spectroscopy (NIRS) has potential as a rapid, accurate and economical alternative method for cannabinoid analysis. Using chromatographic data on 12 therapeutically relevant cannabinoids together with spectral output from a diffuse reflectance NIRS device, predictive chemometric models were built for major and minor cannabinoids using dried, homogenised C. sativa inflorescences from a diverse panel of 84 accessions. Coefficients of determination (r²) of the validation models for 10 of the 12 cannabinoids ranged from 0.8 to 0.95, with models for major cannabinoids showing best performance. NIRS was able to discriminate between neutral and acidic forms of cannabinoids as well as between C3-alkyl and C5-alkyl cannabinoids. The results show that NIRS, when used in conjunction with chemometrics, is a promising method to quantify cannabinoids in raw materials with good predictive results.
Dengue virus (DENV) infection is one of the most widely spread flavivirus infections. Despite the fatality it could cause, no antiviral treatment is currently available to treat the disease. Hence, this study aimed to repurpose old drugs as novel DENV NS3 inhibitors. Ligand-based (L-B) and proteochemometric (PCM) prediction models were built using 62,354 bioactivity data to screen for potential NS3 inhibitors. Selected drugs were then subjected to the foci forming unit reduction assay (FFURA) and protease inhibition assay. Finally, molecular docking was performed to validate these results. The in silico studies revealed that both models performed well in the internal and external validations. However, the L-B model showed better accuracy in the external validation in terms of its sensitivity (0.671). In the in vitro validation, all drugs (zileuton, trimethadione, and linalool) were able to moderately inhibit the viral activities at the highest concentration tested. Zileuton showed comparable results with linalool when tested at 2 mM against the DENV NS3 protease, with a reduction of protease activity at 17.89 and 18.42%, respectively. Two new compounds were also proposed through the combination of the selected drugs, which are ziltri (zilueton + trimethadione) and zilool (zileuton + linalool). The molecular docking study confirms the in vitro observations where all drugs and proposed compounds were able to achieve binding affinity ≥ −4.1 kcal/mol, with ziltri showing the highest affinity at −7.7 kcal/mol, surpassing the control, panduratin A. The occupation of both S1 and S2 subpockets of NS2B-NS3 may be essential and a reason for the lower binding energy shown by the proposed compounds compared to the screened drugs. Based on the results, this study provided five potential new lead compounds (ziltri, zilool, zileuton, linalool, and trimethadione) for DENV that could be modified further.
Diabetic foot ulcer (DFU) is a common complication of diabetes mellitus which can cause infection, amputation and even death. One of many treatments that can be applied to support the DFU healing processes is by using wound dressings. Bacterial cellulose (BC) is a good material to be used as a wound dressing. However, some of the limitations of BC to be applied as wound dressing are does not possess antibacterial properties and support the healing process. Andaliman (Zanthoxylum acanthopodium) is known to have antioxidant, antibacterial and anti-inflammatory abilities that can support BC as a wound dressing. This research focused on the manufacture of BC/Z. acanthopodium microencapsulated wound dressing composites and evaluate their potential as a DFU wound dressing with a variety of gelatin composition in microencapsulation. The results of FTIR and SEM analysis showed that the Z. acanthopodium impregnation process in BC was successful. The variation of gelatine that used in microencapsulation affected the morphological and effectiveness of the wound dressing. However, overall, the wound dressings showed good antibacterial effect on E. coli and S. aureus bacteria and accelerating the wound closure process 8 times faster (BCAMc12) on the 17th day compared to wounds that did not receive any treatment.
(-)-Cannabidiol is a class of non-psychoactive plant cannabinoids derived from cannabis plants. Currently, Epidiolex (Cannabidiol) has been approved by the FDA for the treatment of two rare and severe forms of epilepsy related diseases, namely Lennox-Gastaut syndrome (LGS) and Dravet (DS). In addition, Cannabidiol and its structural analogues have received increasing attention due to their potential therapeutic effects such as neuroprotection, anti-epilepsy, anti-inflammation, anti-anxiety, and anti-cancer. Based on literature review, no comprehensive reviews on the synthesis of Cannabidiol and its derivatives have been found in recent years. Therefore, this article summarizes the published synthesis methods of Cannabidiol and the synthesis routes of Cannabidiol derivatives, and introduces the biological activities of some Cannabidiol analogues that have been studied extensively and have significant activities.
Steroids are an important class of biomolecules with diverse roles and functions. Besides being important as structural and signaling molecules, these molecules hold promise against numerous disorders, including cardiovascular conditions, cancer, inflammation and autoimmune disorders. Many investigations have demonstrated that steroidal frameworks may provide lipid solubility, receptor selectivity or membrane binding properties to non-steroidal pharmacophores. However, the therapeutic use of steroids can be dangerous when they're used incorrectly. Additionally, misconceptions about steroids among athletes or recreational users can lead to steroid abuse and poor health outcomes. Steroids and their Medicinal Potential discusses the classification, distribution, biosynthesis, chemical synthesis and semi-synthesis of different steroids. The medicinal potential of each class is exhaustively discussed in different chapters. The latest advances and developments in steroid-based drug discovery are also discussed thoroughly. The book aims to address general questions and concerns about steroids, providing readers a useful resource on the subject. Key Features -Provides comprehensive coverage on all aspects of steroids including steroid chemistry, biochemistry, medicinal potential, drug discovery and advances in target-binding interactions of steroid-based drugs -Includes chapters dedicated to anabolic steroids and their abuse -Designed as an accessible source of information for understanding steroidal drugs with structured chapters -Includes references for advanced readers
The characterisation of cannabis plants, especially the determination of specific phytocannabinoids, has gained enormous importance in the last decade, mainly due to the recent changes in cannabis control in several countries or states. This is particularly relevant for the forensic, medical or recreative industry to have a rapid, inexpensive, and reliable methodology to identify and quantify phytocannabinoids. Furthermore, spiking cannabis products with Δ8-tetrahydrocannabinol (THC) is a contemporary trend that demands improving or replacing current methods to include this cannabinoid. The current study presents an ultrasound-assisted solid-liquid extraction followed by high-performance liquid chromatography with diode array detection (HPLC-DAD) methodology to identify and quantify Δ9-THC, Δ8-THC, cannabidiol, cannabinol, Δ9-tetrahydrocannabinolic acid and cannabidiolic acid in cannabis products. The herbal samples were extracted with ethanol:acetonitrile (50:50, v:v) by ultrasonication using only 50 mg of sample. The plant oils were diluted in ethanol. The optimised procedure allowed ≈100% extraction efficiency of the target cannabinoids. The validation assays showed that the method is linear (R2 > 0.997), selective, sensitive, precise and accurate, with suitable limits of detection (0.125-0.250 µg mL-1) and quantification (0.500 µg mL-1). The method was successfully applied to cannabis samples, demonstrating its suitability for routine analyses. This contribution follows the current demand for fast and straightforward analysis services of this plant and its derivatives, using small amounts of sample. The present study compares very favourably against other works, particularly in regards to the extraction efficiency, speed of the overall procedure, method sensitivity, and ability to monitor Δ8-THC spiked samples using a novel solvent mixture.
Volatiles are important quality components in tea (Camellia sinensis) flowers. Albino tea plants are mutant tea plants with diverse abnormal metabolisms. However, whether the metabolisms of volatiles in tea flowers from albino cultivars are abnormal remains unclear. In this study, headspace solid-phase microextraction coupled to gas chromatography-mass spectrometry and aroma evaluation were conducted to investigate the volatile composition and aroma of tea flowers from three albino cultivars (i.e., Baiye No.1, Huangjinya, and Yujinxiang) and one non-albino cultivar (i.e., Jiukeng). The results indicated that tea flowers shared the majority of volatiles but their relative abundances were different. Twelve differential compounds were screened out by partial least squares discriminant analysis. Linalool was the one with the highest relative abundance in three out of the four tea flowers, while acetophenone was the one with the highest relative abundance in tea flowers from Huangjinya. Aroma evaluation indicated that tea flowers from Huangjinya smelt sweetest among them. Partial least squares regression analysis revealed that acetophenone and (R)-1-phenylethanol were positively associated with the sweet smell, while methyl salicylate, 2-heptanol, (E)-2-hexenal, nonanal, and 2-pentanol were positively associated with the green smell. The results enhance our understanding of the volatiles and aroma of tea flowers from albino cultivars.
The phytochemical content and the antioxidant activity in the inflorescences of six industrial hemp (Cannabis sativa L.) genotypes, four monoecious (Codimono, Carmaleonte, Futura 75, and Santhica 27), and two dioecious (Fibrante and Carmagnola Selezionata), were assessed for three consecutive years from 2018 to 2020. The total phenolic content, total flavonoid content, and antioxidant activity were determined by spectrophotometric measurements, whereas HPLC and GC/MS were used to identify and quantify the phenolic compounds, terpenes, cannabinoids, tocopherols, and phytosterols. All the measured traits were significantly affected by genotype (G), cropping year (Y), and their interaction (G × Y), although the Y effect prevailed as a source of variation, ranging from 50.1% to 88.5% for all the metabolites except cannabinoids, which were equally affected by G, Y, and G × Y interaction (33.9%, 36.5%, and 21.4%, respectively). The dioecious genotypes presented a more constant performance over the three years compared to the monoecious genotypes, with the highest and most stable phytochemical content observed in the inflorescences of Fibrante, which was characterized by the highest levels of cannabidiol, α-humulene and β-caryophyllene, which may confer on the inflorescences of this genotype a great economic value due to the important pharmacological properties of these metabolites. Conversely, the inflorescences of Santhica 27 were characterized by the lowest accumulation of phytochemicals over the cropping years, with the notable exception of cannabigerol, a cannabinoid that exhibits a wide range of biological activities, which was found at its highest level in this genotype. Overall, these findings can be used by breeders in future programs aimed at the selection of new hemp genotypes with improved levels of phytochemicals in their inflorescences, which can provide better health and industrial benefits.
O tremor essencial é um dos distúrbios de movimento mais comuns na população geral, gerando prejuízo significativo na qualidade de vida dos acometidos. Atualmente, as opções terapêuticas convencionais são escassas e associadas a efeitos colaterais que limitam sua adesão, especialmente em jovens. Há um crescente número de estudos que avaliam o potencial terapêutico de compostos provenientes da planta Cannabis sativa em tremores de diferentes etiologias incluindo Doença de Parkinson, Esclerose múltipla e Tremor Essencial. Este relato de caso visa elucidar o caso de um paciente jovem com diagnóstico de tremor essencial e sua resposta ao tratamento com óleo de espectro completo, rico em Canabidiol, mensurada com auxílio do Questionário de Qualidade de Vida no Tremor Essencial (Quality of Life in Essential Tremor Questionnaire - QUEST).
Use of cannabidiol (CBD) in humans has increased considerably in recent years. While currently available studies suggest that CBD is relatively safe for human consumption, data from publicly available studies on CBD conducted according to modern testing guidelines are lacking. In the current study, the potential for toxicity following repeated oral exposure to hemp-derived CBD isolate was evaluated in male and female Sprague Dawley rats. No adverse treatment-related effects were observed following administration of CBD via oral gavage for 14 and 90 days at concentrations up to 150 and 140 mg/kg-bw/d, respectively. Microscopic liver and adrenal gland changes observed in the 90-day study were determined to be resolved after a 28-day recovery period. CBD was well tolerated at these dose levels, and the results of this study are comparable to findings reported in unpublished studies conducted with other CBD isolates. The current studies were conducted as part of a broader research program to examine the safety of CBD.
Feeding on plant-derived sugars is an essential component of mosquito biology that affects key aspects of their lives such as survival, metabolism, and reproduction. Mosquitoes locate plants to feed on using olfactory and visual cues. Aedes aegypti and Aedes albopictus are two invasive mosquito species to the US, and are vectors of diseases such as dengue fever, chikungunya, and Zika. These species live in heavily populated, urban areas, where they have a high accessibility to human hosts as well as to plants in backyards and town landscapes. Therefore, it is important to understand what plants may attract or repel mosquitoes to inform citizens and municipal authorities accordingly. Here, we analyzed Ae. aegypti and Ae. albopictus sugar-feeding behavior with eleven different commonly planted ornamental plant species. We then assessed feeding activity using the anthrone method and identified volatile composition of plant headspace using gas-chromatography mass-spectroscopy. Finally, we determined the sugar-feeding activity of field caught mosquitoes using the plant DNA barcoding technique and compared these results with the eleven ornamental species tested in the laboratory. The potential for application to disease vector control is also discussed.
Bei sogenannten „therapieresistenten“ Erkrankungen kommen traditionell auch Substanzen zum Einsatz, die sonst entweder keine Anwendung in der Medizin finden oder deren Wirksamkeit und Sicherheit bisher lediglich in (zum Teil gänzlich) anderen Indikationen gezeigt wurde. Ihre Anwendung stellt daher immer eine Off-Label-Therapie dar, in Einzelfällen ist sie sogar durch das Gesetz untersagt. Dass sie dennoch zum Einsatz kommen, ist dem Wunsch geschuldet, nach dem Ausschöpfen anderer, geprüfter und zugelassener Arzneimittel, betroffenen Patienten doch irgendein Behandlungsangebot machen zu können. Einer breiteren Anwendung dieser Substanzen bei therapieresistenter Depression steht die meist sehr schwache Datenlage gegenüber. Potentieller Nutzen und Risiken sind daher in jedem Einzelfall sorgfältig gegeneinander abzuwägen.
Calophyllum inophyllum is used in traditional medicine to treat several diseases and conditions. Several studies have attempted to isolate useful compounds from various parts of this plant. However, the phytochemical constituents of C. inophyllum flower have not been extensively studied. This pioneering study focused on the chemical composition of C. inophyllum flower analyzed by gas chromatography-electron ionization/mass spectrometry (GC-EI/MS) and the antibacterial effects of C. inophyllum flower extracted with organic solvents. Phytochemical compounds were obtained from C. inophyllum flower via maceration with sequential extraction using hexane, ethyl acetate, and methanol, respectively. Phytochemical components of total phenolic (TP), total flavonoid (TF), and total saponin (TSC) contents were determined by colorimetric methods and each extract was found to be rich in phenolic, flavonoid, and saponin constituents. The antibacterial activities of the extracts were studied by disk diffusion method. The minimum inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) assays were used to address the potentials of extracts. All extracts were active against pathogenic bacteria at different concentrations, and were especially active against Salmonella tyhpi. In addition, the hexane extract exhibited the lowest MIC and MBC of 0.098 and 3.12 mg/mL, respectively, against B. cereus based on the antibacterial dilution method. The correlation analysis indicated a negative relationship between the flavonoid content and the inhibition zone of Salmonella typhi, with a significant value of p < 0.05. On the contrary, a positive relationship between the saponin content and the inhibition zone Klebsiella pneumoniae. These results showed that C. inophyllum flower extracts are rich of bioactive compounds such as phytol, eugenol, caryophyllene oxide, α-copaene, α-muurolene, β-caryophyllene, β-amysin, farnesol, palmitic acid, and cadinene derivatives.
The herb cannabis is derived from the Old World species Cannabis sativa L. Cannabis indica and C. ruderalis may also merit species status. Cannabis has a history as an analgesic agent that spans at least 4000 years, including a century of usage in mainstream Western medicine. Quality control issues, and ultimately political fiat eliminated this agent from the modern pharmacopoeia, but it is now resurgent. The reasons lie in the remarkable pharmacological properties of the herb and new scientific research that reveals the inextricable link that cannabinoids possess with our own internal biochemistry. In essence, the cannabinoids form a system in parallel with that of the endogenous opioids in modulating pain. More important, cannabis and its endogenous and synthetic counterparts may be uniquely effective in pain syndromes in which opiates and other analgesics fail.
Cannabis (Cannabis sativa) plants produce and accumulate a terpene-rich resin in glandular trichomes, which are abundant on the surface of the female inflorescence. Bouquets of different monoterpenes and sesquiterpenes are important components of cannabis resin as they define some of the unique organoleptic properties and may also influence medicinal qualities of different cannabis strains and varieties. Transcriptome analysis of trichomes of the cannabis hemp variety 'Finola' revealed sequences of all stages of terpene biosynthesis. Nine cannabis terpene synthases (CsTPS) were identified in subfamilies TPS-a and TPS-b. Functional characterization identified mono-and sesqui-TPS, whose products collectively comprise most of the terpenes of 'Finola' resin, including major compounds such as β-myr-cene, (E)-β-ocimene, (-)-limonene, (+)-α-pinene, β-caryophyllene, and α-humulene. Transcripts associated with terpene biosynthesis are highly expressed in trichomes compared to non-resin producing tissues. Knowledge of the CsTPS gene family may offer opportunities for selection and improvement of terpene profiles of interest in different cannabis strains and varieties.
Introduction: With laws changing around the world regarding the legal status of Cannabis sativa (cannabis) it is important to develop objective classification systems that help explain the chemical variation found among various cultivars. Currently cannabis cultivars are named using obscure and inconsistent nomenclature. Terpenoids, responsible for the aroma of cannabis, are a useful group of compounds for distinguishing cannabis cultivars with similar cannabinoid content.
Methods: In this study we analyzed terpenoid content of cannabis samples obtained from a single medical cannabis dispensary in California over the course of a year. Terpenoids were quantified by gas chromatography with flame ionization detection and peak identification was confirmed with gas chromatography mass spectrometry. Quantitative data from 16 major terpenoids were analyzed using hierarchical clustering analysis (HCA), principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA).
Results: A total of 233 samples representing 30 cultivars were used to develop a classification scheme based on quantitative data, HCA, PCA, and OPLS-DA. Initially cultivars were divided into five major groups, which were subdivided into 13 classes based on differences in terpenoid profile. Different classification models were compared with PLS-DA and found to perform best when many representative samples of a particular class were included.
Conclusion: A hierarchy of terpenoid chemotypes was observed in the data set. Some cultivars fit into distinct chemotypes, whereas others seemed to represent a continuum of chemotypes. This study has demonstrated an approach to classifying cannabis cultivars based on terpenoid profile.
This short communication examines the question whether the experimental data presented in a study by Merrick et al. are of clinical relevance. These authors found that cannabidiol (CBD), a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta-8-THC and delta-9-THC to a relevant degree. They concluded that “the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a positive physiological response.” They issued a warning concerning oral use of CBD and recommend the development of other delivery methods. However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC. On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. In addition, administration of CBD did not result in detectable THC blood concentrations. Thus, there is no reason to avoid oral use of CBD, which has been demonstrated to be a safe means of administration of CBD, even at very high doses.
Many plant species produce mixtures of odorous and volatile compounds known as essential oils (EOs). These mixtures play important roles in Nature and have been utilized by mankind for different purposes, such as pharmaceuticals, agrochemicals, aromatherapy, and food flavorants. There are more than 3000 EOs reported in the literature, with approximately 300 in commercial use, including the EOs from Eucalyptus species. Most EOs from Eucalyptus species are rich in monoterpenes and many have found applications in pharmaceuticals, agrochemicals, food flavorants, and perfumes. Such applications are related to their diverse biological and organoleptic properties. In this study, we review the latest information concerning the chemical composition and biological activities of EOs from different species of Eucalyptus. Among the 900 species and subspecies of the Eucalyptus genus, we examined 68 species. The studies associated with these species were conducted in 27 countries. We have focused on the antimicrobial, acaricidal, insecticidal and herbicidal activities, hoping that such information will contribute to the development of research in this field. It is also intended that the information described in this study can be useful in the rationalization of the use of Eucalyptus EOs as components for pharmaceutical and agrochemical applications as well as food preservatives and flavorants.
Aims:
We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120.
Main methods:
Male Swiss mice received gp120, IL-1β or TNF-α intrathecally or sterile saline as a control. A mechanicalsensitivity test was performed at 2 and 3h after the injection. Spinal cord and blood samples were isolated for protein quantification.
Key findings:
Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL-1β and IL-10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF-α and IL-1β-induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4h after intrathecal IL-1β injection.
Significance:
These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL-1β and IL-10, and that prior administration of limonene inhibits these changes. Also limonene modulates the activation of SOD expression in the spinal cord after spinal IL-1β application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF-α and IL-1β emphasizes the anti-inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences.
Objective(s)
Cerebral ischemia is often associated with cognitive impairment. Oxidative stress has a crucial role in the memory deficit following ischemia/reperfusion injury. α-Terpineol is a monoterpenoid with anti-inflammatory and antioxidant effects. This study was carried out to investigate the effect of α-terpineol against memory impairment following cerebral ischemia in rats.
Materials and Methods
Cerebral ischemia was induced by transient bilateral common carotid artery occlusion in male Wistar rats. The rats were allocated to sham, ischemia, and α-terpineol-treated groups. α-Terpineol was given at doses of 50, 100, and 200 mg/kg, IP once daily for 7 days post ischemia. Morris water maze (MWM) test was used to assess spatial memory and in vivo extracellular recording of long-term potentiation (LTP) in the hippocampal dentate gyrus was carried out to evaluate synaptic plasticity. Malondialdehyde (MDA) was measured to assess the extent of lipid peroxidation in the hippocampus.
Results
In MWM test, α-terpineol (100 mg/kg, IP) significantly decreased the escape latency during training trials (P<0.01). In addition, α-terpineol increased the number of crossings over the platform location and decreased average proximity to the target in probe trial (P<0.05). In electrophysiological recording, α-terpineol (100 mg/kg) facilitated the induction of LTP in the hippocampus which was persistent over 2 hr. α-Terpineol (100 and 200 mg/kg) also significantly lowered hippocampal MDA levels in rats subjected to cerebral ischemia.
Conclusion
These findings indicate that α-terpineol improves cerebral ischemia-related memory impairment in rats through the facilitation of LTP and suppression of lipid peroxidation in the hippocampus.
Aim:
The biopotential of the essential oils of the Greek aromatic plants Satureja thymbra and Satureja parnassica were investigated, together with their major components carvacrol, thymol, γ-terpinene and p-cymene.
Materials and methods:
Antioxidant and cancer cell cytotoxic properties were determined using 2,2-diphenyl-1-picrylhydrazyl and sulforhodamine B assays, respectively. The antiproliferative potential was studied against the MCF-7, A549, HepG2 and Hep3B cell lines.
Results:
S. thymbra oil possessed stronger antioxidant and antiproliferative capacity when tested on MCF-7 cells compared to S. parnassica oil. Thymol exhibited two-fold greater antioxidant potency than carvacrol, whereas γ-terpinene and p-cymene had no significant effect. Carvacrol was the most potent antiproliferative agent against A549 cells, while Hep3B cells were most sensitive to thymol. p-Cymene and γ-terpinene demonstrated negligible bioactivity.
Conclusion:
S. thymbra and S. parnassica essential oils exhibit significant but diverse antioxidant and antiproliferative activities, mainly attributed to their main components, carvacrol and thymol.
Natural bicyclic sesquiterpenes, β-caryophyllene (BCP) and β-caryophyllene oxide (BCPO), are present in a large number of plants worldwide. Both BCP and BCPO (BCP(O)) possess significant anticancer activities, affecting growth and proliferation of numerous cancer cells. Nevertheless, their antineoplastic effects have hardly been investigated in vivo. In addition, both compounds potentiate the classical drug efficacy by augmenting their concentrations inside the cells. The mechanisms underlying the anticancer activities of these sesquiterpenes are poorly described. BCP is a phytocannabinoid with strong affinity to cannabinoid receptor type 2 (CB2), but not cannabinoid receptor type 1 (CB1). In opposite, BCP oxidation derivative, BCPO, does not exhibit CB1/2 binding, thus the mechanism of its action is not related to endocannabinoid system (ECS) machinery. It is known that BCPO alters several key pathways for cancer development, such as mitogen-activated protein kinase (MAPK), PI3K/AKT/mTOR/S6K1 and STAT3 pathways. In addition, treatment with this compound reduces the expression of procancer genes/proteins, while increases the levels of those with proapoptotic properties. The selective activation of CB2 may be considered a novel strategy in pain treatment, devoid of psychoactive side effects associated with CB1 stimulation. Thus, BCP as selective CB2 activator may be taken into account as potential natural analgesic drug. Moreover, due to the fact that chronic pain is often an element of cancer disease, the double activity of BCP, anticancer and analgesic, as well as its beneficial influence on the efficacy of classical chemotherapeutics, is particularly valuable in oncology. This review is focused on anticancer and analgesic activities of BCP and BCPO, the mechanisms of their actions, and potential therapeutic utility.
Introduction: There is a large disparity between the ''cultural'' language used by patients using cannabis for self-medication and the ''chemical'' language applied by scientists to get a deeper understanding of cannabis effects in laboratory and clinical studies. The distinction between Sativa and Indica types of cannabis, and the different biological effects associated with them, is a major example of this. Despite the widespread use of cannabis by self-medicating patients, scientific studies are yet to identify the biochemical markers that can sufficiently explain differences between cannabis varieties. Methods: A metabolomics approach, combining detailed chemical composition data with cultural information available for a wide range of cannabis samples, can help to bridge the existing gap between scientists and patients. Such an approach could be helpful for decision-making, for example, when identifying which varieties of cannabis should be made legally available under national medicinal cannabis programs. In our study, we analyzed 460 cannabis accessions obtained from multiple sources in The Netherlands, including hemp-and drug-type cannabis. Results: Based on gas chromatography analysis of 44 major terpenes and cannabinoids present in these samples , followed by Multivariate Data Analysis of the resulting chromatographic data, we were able to identify the cannabis constituents that may act as markers for distinction between Indica and Sativa. This information was subsequently used to map the current chemical diversity of cannabis products available within the Dutch medicinal cannabis program, and to introduce a new variety missing from the existing product range. Conclusion: This study represents the analysis of the widest range of cannabis constituents published to date. Our results indicate the usefulness of a metabolomics approach for chemotaxonomic mapping of cannabis varieties for medical use.
(-)-Guaiol, generally known as an antibacterial compound, has been found in many medicinal plants. Its roles in tumor suppression are still under investigation. In the study, we mainly focused on exploring its applications in dealing with non-small cell lung cancer (NSCLC) and the underlying mechanisms. Here, we show that (-)-Guaiol significantly inhibits cell growth of NSCLC cells both in vitro and in vivo. Further high throughput analysis reveals that RAD51, a pivotal factor in homologous recombination repair, is a potential target for it. The following mechanism studies show that (-)-Guaiol is involved in cell autophagy to regulate the expression of RAD51, leading to double-strand breaks triggered cell apoptosis. Moreover, targeting RAD51, which is highly overexpressed in the lung adenocarcinoma tissues, can significantly increase the chemosensitivity of NSCLC cells to (-)-Guaiol both in vitro and in vivo. All in all, our studies provide an attractive insight in applying (-)-Guaiol into NSCLC treatments and further suggest that knockdown of oncogenic RAD51 will greatly enhance the chemosensitivity of patients with NSCLC.
In the 1960s several interesting compounds were isolated from the Cannabis plant. Today over 100 cannabinoids have been identified, across numerous varieties of Cannabis, which are structurally related to the main psychoactive ingredient ?9-tetrahydrocannabinol. This plant is a treasure trove of pharmacological compounds. Many of these compounds demonstrate unique properties and mechanisms apart from those of ?9-tetrahydrocannabinol; nonpsychotropic cannabidiol especially is being explored in pediatric clinical trials for the treatment of epilepsy. Cannabidiol and other cannabinoids may also represent nontoxic treatments with an exceedingly low potential for developing drug-addiction-related disorders. The aroma of Cannabis comprises over 120 terpenoid compounds, which are potent mediators of mammalian behavior when delivered at ambient air levels. ?-Caryophyllene is one of the most abundant terpenoids in the plant kingdom with cannabinoid receptor activity and has been shown to reduce cocaine self-administration in animals. The active ingredients on the Cannabis plant interact with or stimulate the endocannabinoid system, which underlies the mechanisms explaining potential benefits in drug abuse and addiction treatments.
Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association.
Δ(9)-tetrahydrocannabinolic acid A (THCA-A) is the acidic precursor of Δ(9)-tetrahydrocannabinol (THC), the main psychoactive compound found in Cannabis sativa. THCA-A is biosynthesized and accumulated in glandular trichomes present on flowers and leaves, where it serves protective functions and can represent up to 90% of the total THC contained in the plant. THCA-A slowly decarboxylates to form THC during storage and fermentation and can further degrade to cannabinol. Decarboxylation also occurs rapidly during baking of edibles, smoking, or vaporizing, the most common ways in which the general population consumes Cannabis. Contrary to THC, THCA-A does not elicit psychoactive effects in humans and, perhaps for this reason, its pharmacological value is often neglected. In fact, many studies use the term "THCA" to refer indistinctly to several acid derivatives of THC. Despite this perception, many in vitro studies seem to indicate that THCA-A interacts with a number of molecular targets and displays a robust pharmacological profile that includes potential anti-inflammatory, immunomodulatory, neuroprotective, and antineoplastic properties. Moreover, the few in vivo studies performed with THCA-A indicate that this compound exerts pharmacological actions in rodents, likely by engaging type-1 cannabinoid (CB1) receptors. Although these findings may seem counterintuitive due to the lack of cannabinoid-related psychoactivity, a careful perusal of the available literature yields a plausible explanation to this conundrum and points toward novel therapeutic perspectives for raw, unheated Cannabis preparations in humans.
In order to complete a genetic model for the inheritance of chemotype in Cannabis, this paper explores the regulation of the propyl-/pentyl cannabinoid ratio. Plants almost pure in compounds with a C5 side chain are by far the most common, and such a chemotype can be considered a wild-type condition. Mutant progenitors with higher levels of the rarer cannabinoid THC-C3 (tetrahydrocannabivarin) were identified. Their propyl cannabinoid proportion in the total cannabinoid fraction (PC3) ranged from 14 to 69 %, which, through selective inbreeding, could be increased to highly specific lineage maxima. Inbred plants with maximised PC3 derived from the different progenitors, were then crossed with a pure C5 wild type and the PC3 distribution patterns of the F2s examined. Distinct patterns, compatible with oligogenic and polygenic segregation appeared. It was hypothesised that the PC3 regulating loci of the six source progenitors would be at least partially different, complementary, and additive in their phenotypical effect. So, high PC3 offspring from the different lineages were mutually crossed. Inbred lines derived from multi-cross hybrid combinations reached unprecedented PC3 levels of up to 96 % which supports the hypothesis. For the regulation of C3/C5 ratios, a model of a multiple locus A
1–A
2–…A
n is proposed, with the pentyl- and propyl cannabinoid pathway being enhanced by alleles A
pe1−n and A
pr1−n, respectively.
Objectives:
Dependence and tolerance to opioid analgesics are major problems limiting their clinical application. α-Terpineol is a monoterpenoid alcohol with neuroprotective effects which is found in several medicinal plants such as Myrtus communis, Laurus nobilis, and Stachys byzantina. It has been shown that some of these medicinal plants such as S. byzantina attenuate dependence and tolerance to morphine. Since α-terpineol is one of the bioactive phytochemical constituent of these medicinal plants, the present study was conducted to investigate the effects of α-terpineol on morphine-induced dependence and tolerance in mice.
Materials and methods:
The mice were rendered dependent or tolerant to morphine by a 3-day administration schedule. The hot-plate test and naloxone-induced withdrawal syndrome were used to evaluate tolerance and dependence on morphine, respectively. To investigate a possible role for nitric oxide (NO) in the protective effect of α-terpineol, the NO synthase inhibitor, L-N(G)-nitroarginine methyl ester (L-NAME) and NO precursor, L-arginine, were used.
Results:
Administration of α-terpineol (5, 10, and 20 mg/kg, IP) significantly decreased the number of jumps in morphine dependent animals. Moreover, α-terpineol (20 and 40 mg/kg, IP) attenuated tolerance to the analgesic effect of morphine. The inhibitory effects of α-terpineol on morphine-induced dependence and tolerance were enhanced by pretreatment with L-NAME (10 mg/kg, IP). However, L-arginine (300 mg/kg, IP) antagonized the protective effects of α-terpineol on dependence and tolerance to morphine.
Conclusion:
These findings indicate that α-terpineol prevents the development of dependence and tolerance to morphine probably through the influence on NO production.
In 2010 a review by Hazekamp and Grotenhermen covered controlled clinical trials of the years 2006-2009 on cannabis-based medicines, which followed the example of the review by Ben Amar (2006). The current review reports on the more recent clinical data available from 2010-2014. A systematic search was performed in the scientific database of PubMed, focused on clinical studies that were randomized, (double) blinded, and placebo-controlled.
The key words used were: cannabis, marijuana, marihuana, hashish, cannabinoid(s), tetrahydrocannabinol, THC, CBD, dronabinol, Marinol, nabilone, Cannador, nabiximols and Sativex. For the final selection, only properly controlled clinical trials were retained. Open-label studies were excluded, except if they were a direct continuation of a study discussed here.
Thirty-two controlled studies evaluating the therapeutic effects of cannabinoids were identified. For each clinical trial, the country where the project was held, the number of patients assessed, the type of study and comparisons done, the products and the dosages used, their efficacy and their adverse effects are described. Based on the clinical results, cannabinoids present an interesting therapeutic potential mainly as analgesics in chronic neuropathic pain and spasticity in multiple sclerosis. But a range of other indications also seem promising. CBD (cannabidiol) emerges as another valuable cannabinoid for therapeutic purposes besides THC.
The control of hyperlipidemia plays a central role in cardiovascular disease. Previously, we have shown that camphene, a constituent of mastic gum oil, lowers cholesterol and triglycerides (TG) in the plasma of hyperlipidemic rats without affecting HMG-CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins. In the present study, we examine the mechanism by which camphene exerts its hypolipidemic action. We evaluated the effect of camphene on the de novo synthesis of cholesterol and TG from [14C]-acetate in HepG2 cells, along with the statin mevinolin. Camphene inhibited the biosynthesis of cholesterol in a concentration-dependent manner, and a maximal inhibition of 39% was observed at 100 μM while mevinolin nearly abolished cholesterol biosynthesis. Moreover, treatment with camphene reduced TG by 34% and increased apolipoprotein AI expression. In contrast, mevinolin increased TG by 26% and had a modest effect on apolipoprotein AI expression. To evaluate the mode of action of camphene, we examined its effects on the expression of SREBP-1, which affects TG biosynthesis and SREBP-2, which mostly affects sterol synthesis. Interestingly, camphene increased the nuclear translocation of the mature form of SREBP-1 while mevinolin was found to increase the amount of the mature form of SREBP-2. The effect of camphene is most likely regulated through SREBP-1 by affecting MTP levels in response to a decrease in the intracellular cholesterol. We propose that camphene upregulates SREBP-1 expression and MTP inhibition is likely to be a probable mechanism whereby camphene exerts its hypolipidemic effect.
Objective:
Acute administration of cannabinoid CB1 receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users. Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice.
Methods:
Adult male DIO and lean mice were treated daily with vehicle or THC (2mg/kg for 3 weeks and 4 mg/kg for 1 additional week). Body weight, fat mass, energy intake, locomotor activity, whole gut transit and gut microbiota were measured longitudinally.
Results:
THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC. THC had no effect on locomotor activity or whole gut transit in either lean or DIO mice.
Conclusions:
Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity.
Oxidative stress, as mediated by ROS, is a significant factor in initiating the development of age-associated cataracts; D-limonene is a common natural terpene with powerful antioxidative properties which occurs naturally in a wide variety of living organisms. It has been shown to have antioxidant effect; we found that D-limonene can effectively prevent the oxidative damage caused by H
2
O
2
and propose that the main mechanism underlying the inhibitory effects of D-limonene is the inhibition of HLECs apoptosis. In the present study, we used confocal-fluorescence microscopy, flow cytometry analysis, Hoechst staining, H
2
DCFDA staining, transmission electron microscopy, and immunoblot analysis; the results revealed that slightly higher concentrations of D-limonene (125–1800
μ
M) reduced the H
2
O
2
-induced ROS generation and inhibited the H
2
O
2
-induced caspase-3 and caspase-9 activation and decreased the Bcl-2/Bax ratio. Furthermore, it inhibited H
2
O
2
-induced p38 MAPK phosphorylation. Thus, we conclude that D-limonene could effectively protect HLECs from H
2
O
2
-induced oxidative stress and that its antioxidative effect is significant, thereby increasing the cell survival rate.
(-)-Linalool is the major floral scent occurring mainly in families Lamiaceae, Lauraceae and Rutaceae and is the main active compound of lavender oil. The purpose of this study was to reveal the influence of subchronic systemic treatment with (-)-linalool on the metabolic activity of CYP2A, 2B, 2C6, 2C11 and 3A in rat liver microsomes (RLM). The second aim was to reveal possible inhibitory effect of (-)-linalool on CYP2C6 in vitro. Wistar albino male rats were treated with (-)-linalool intragastrically in doses of 40, 120, and 360 mg/kg/day for 13 days. Treatment with (-)-linalool at the dose of 360 mg/kg increased the metabolic activity of CYP2A assessed with testosterone as a probe substrate. (-)-Linalool showed weak competitive inhibition of CYP2C6 in rat liver microsomes, with IC50 of 84 μM with use of diclofenac as a probe substrate.
Canniprene (1), an isoprenylated bibenzyl unique to Cannabis sativa, can be vaporized and therefore potentially inhaled from marijuana. Canniprene (1) potently inhibited the production of inflammatory eicosanoids via the 5-lipoxygenase pathway (IC50 0.4 μM) and also affected the generation of prostaglandins via the cyclooxygenase/microsomal prostaglandin E2 synthase pathway (IC50 10 μM), while the related spiranoid bibenzyls cannabispiranol (2) and cannabispirenone (3) were almost inactive in these bioassays. The concentration of canniprene (1) was investigated in the leaves of 160 strains of C. sativa, showing wide variations, from traces to >0.2%, but no correlation was found between its accumulation and a specific phytocannabinoid profile.
Background and aims:
Beta-caryophyllene (BCP) is a plant-derived FDA approved food additive with anti-inflammatory properties. Some of its beneficial effects in vivo reported to involve activation of cannabinoid 2 receptors (CB2) that are predominantly expressed in immune cells. Herein, we evaluated the translational potential of BCP using a well-established model of chronic and binge alcohol-induced liver injury.
Methods:
In this study we investigated the effects of BCP on liver injury induced by chronic plus binge alcohol feeding in mice in vivo by using biochemical assays, real-time PCR and histology analyses. Serum and hepatic BCP levels were also determined by GC/MS.
Results:
Chronic treatment with BCP attenuated the chronic and binge alcohol-induced liver injury and inflammation by attenuating the pro-inflammatory phenotypic `M1` switch of Kupffer cells and by decreasing the expression of vascular adhesion molecules ICAM-1, E-Selectin and P-Selectin, as well as the neutrophil infiltration. It also beneficially influenced hepatic metabolic dysregulation (steatosis, protein hyperacetylation, and PPAR-ɑ signaling). The above mentioned protective effects of BCP against alcohol-induced liver injury were attenuated in CB2 knockout mice, indicating that the beneficial effects of this natural product in liver injury involve CB2 receptor activation. Following acute or chronic administration BCP was detectable both in the serum and liver tissue homogenates but not in the brain.
Conclusions:
Given the safety of BCP in humans this food additive has a high translational potential in treating or preventing hepatic injury associated with oxidative stress, inflammation and steatosis.
The regulatory effect of β-eudesmol, which is an active constituent of Pyeongwee-San (KMP6), is evaluated for allergic reactions induced by mast cell degranulation. Phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated human mast cell line, HMC-1 cells, and compound 48/80-stimulated rat peritoneal mast cells (RPMCs) are used as the in vitro models; mice models of systemic anaphylaxis, ear swelling, and IgE-dependent passive cutaneous anaphylaxis (PCA) are used as the in vivo allergic models. The results demonstrate that β-eudesmol suppressed the histamine and tryptase releases from the PMA plus calcium ionophore A23187-stimulated HMC-1 cells. β-eudesmol inhibits the expression and activity of histidine decarboxylase in the activated HMC-1 cells. In addition, β-eudesmol inhibits the levels of histamine and tryptase released from the compound 48/80-stimulated RPMCs. Furthermore, β-eudesmol decreases the intracellular calcium level in the activated RPMCs. β-eudesmol also decreases the compound 48/80-induced mortality and ear swelling response. β-eudesmol suppresses the serum levels of histamine, IgE, IL-1β, IL-4, IL-5, IL-6, IL-13, and VEGF under PCA mice as well as PCA reactions. Therefore, the results from this study indicate the potential of β-eudesmol as an anti-allergic drug with respect to its pharmacological properties against mast cell-mediated allergic reactions. This article is protected by copyright. All rights reserved.
Cannabis sativa L. is a prolific, but not exclusive, producer of a diverse group of isoprenylated resorcinyl polyketides collectively known as phytocannabinoids. The modular nature of the pathways that merge into the phytocannabinoid chemotype translates in differences in the nature of the resorcinyl side-chain and the degree of oligomerization of the isoprenyl residue, making the definition of phytocannabinoid elusive from a structural standpoint. A biogenetic definition is therefore proposed, splitting the phytocannabinoid chemotype into an alkyl-and a b-aralklyl version, and discussing the relationships between phytocannabinoids from different sources (higher plants, liverworts, fungi). The startling diversity of cannabis phytocannabinoids might be, at least in part, the result of non-enzymatic transformations induced by heat, light, and atmospheric oxygen on a limited set of major constituents (CBG, CBD, D 9-THC and CBC and their corresponding acidic versions), whose degradation is detailed to emphasize this possibility. The diversity of metabotropic (cannabinoid receptors), ionotropic (thermos-TRPs), and transcription factors (PPARs) targeted by phytocannabinoids is discussed. The integrated inventory of these compounds and their biological macromolecular end-points highlights the opportunities that phytocannabinoids offer to access desirable drug-like space beyond the one associated to the narcotic target CB 1 .
Aims:
We aimed to investigate the modulating effect of α-phellandrene on neutrophil migration and mast cell degranulation processes.
Main methods:
Male Wistar rats or Swiss mice were treated p.o. with vehicle (3% Tween 80, p.o.), α-phellandrene (50, 100, or 200mg/kg, p.o.), or dexamethasone (0.5mg/kg, p.o.) 1h before carrageenan injection. Then, the neutrophil migration in 6-day-old air pouches or peritoneal cavities. The leukocyte rolling and adhesion were measured in real time and assessed by intravital microscopy. ELISA was used to detect TNF-α and IL-6 in peritoneal lavage. Compound 48/80-induced mast cell degranulation was assessed in mesenteric rat tissues.
Key findings:
In all the tested doses, α-phellandrene prevented carrageenan-induced neutrophil accumulation (P<0.05). As detected by intravital microscopy, α-phellandrene also inhibited leukocyte rolling and adhesion, as well as significantly inhibited the production of the pro-inflammatory cytokines TNF-α and IL-6. Moreover, the degranulation of compound 48/80-induced mast cells was also inhibited by α-phellandrene (P<0.001).
Significance:
These results suggest that α-phellandrene plays an important role as an anti-inflammatory agent through neutrophil migration modulation and mast cell stabilization.