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.”
... 3 Hacia los años noventa, se determinó que el Δ9-THC ejerce sus efectos a través de su interacción con receptores específicos, denominados receptores CB1 y CB2. 5 Los ligandos endógenos de los receptores a cannabinoides se conocen como endocannabinoides o cannabinoides endógenos. 3,6 En conjunto, los receptores a cannabinoides, los endocannabinoides, y las enzimas necesarias para su síntesis y degradación, conforman al sistema endocannabinoide. ...
... 3,6 A pesar de que el estudio de los fitocannabinoides se ha centrado en el Δ9-THC, el estudio de otros compuestos extraídos de Cannabis ha empezado a cobrar importancia en los últimos años, particularmente el CBD. 5 El CBD es un fitocannabinoide psicoactivo no intoxicante que posee diversas propiedades farmacológicas potencialmente útiles en diversos padecimientos neurológicos y neuropsiquiátricos como la ansiedad, la depresión, la psicosis y la epilepsia, entre otros. 5 Presenta propiedades analgésicas, antiinflamatorias, antipsicóticas, ansiolíticas y anticonvulsivantes, siendo esta última especialmente relevante en el contexto de esta revisión. ...
... 3,6 A pesar de que el estudio de los fitocannabinoides se ha centrado en el Δ9-THC, el estudio de otros compuestos extraídos de Cannabis ha empezado a cobrar importancia en los últimos años, particularmente el CBD. 5 El CBD es un fitocannabinoide psicoactivo no intoxicante que posee diversas propiedades farmacológicas potencialmente útiles en diversos padecimientos neurológicos y neuropsiquiátricos como la ansiedad, la depresión, la psicosis y la epilepsia, entre otros. 5 Presenta propiedades analgésicas, antiinflamatorias, antipsicóticas, ansiolíticas y anticonvulsivantes, siendo esta última especialmente relevante en el contexto de esta revisión. 1 El CBD puede ser producido sintéticamente, lo que permite obtener un compuesto de gran pureza. ...
El cannabidiol (CBD), uno de los principales componentes de la planta Cannabis sativa, tiene propiedades farmacológicas con potencial terapéutico, por lo que ha sido objeto de estudio en los últimos años. Al momento, sólo ha sido aprobado legalmente para el tratamiento de las convulsiones farmacorresistentes en pacientes pediátricos. Los avances realizados en la investigación de las acciones terapéuticas del CBD en epilepsia, se han sustentado principalmente en el empleo de modelos animales. Con estos modelos animales se han evaluado un amplio rango de dosis, con diversas vías y esquemas de administración. A nivel clínico, se han evaluado las interacciones farmacocinéticas/farmacodinámicas entre el CBD y otros fármacos antiepilépticos, a fin de establecer su utilidad como coadyuvante, realizando ajustes de dosis y valorando la presencia de efectos adversos (como la inducción enzimática en el hígado). Además, el CBD es una molécula que interactúa con múltiples blancos moleculares y que además posee propiedades antioxidantes y antiinflamatorias intrínsecas. Esta información nos ha demostrado que los efectos anticonvulsivantes del CBD aún no han sido explorados a detalle en el tratamiento de la epilepsia farmacorresistente, donde las opciones terapéuticas son limitadas. Tampoco se han evaluado los mecanismos moleculares involucrados en sus efectos anticonvulsivos, donde la administración intracerebral del CBD podría facilitar esta tarea. Con el desarrollo de esta revisión, esperamos que el lector tenga una visión general del estado actual del CBD como una molécula con potencial terapéutico para el tratamiento no solo de la epilepsia sino también de la epilepsia farmacorresistente.
... Historically, terpenoid concentrations in cannabis flowers were approximately 1%, with up to 10% found in trichomes, but selective breeding has led to terpenoid flower concentrations exceeding 3.5%. The pharmacological effects and ecological roles of terpenoids, which contribute to the synergistic properties and therefore to the entourage effects of cannabis, have been thoroughly explored in the literature [33][34][35], and eight predominate forms the Terpene Super Classes: myrcene (14), terpinolene (15), ocimene (16), limonene (17), α-pinene (18), humulene (19), linalool (20), and β-caryophyllene (21) ( Figure 5). Advances in molecular biology have furthered the understanding of cannabis genetics. ...
... Historically, terpenoid concentrations in cannabis flowers were approximately 1%, with up to 10% found in trichomes, but selective breeding has led to terpenoid flower concentrations exceeding 3.5%. The pharmacological effects and ecological roles of terpenoids, which contribute to the synergistic properties and therefore to the entourage effects of cannabis, have been thoroughly explored in the literature [33][34][35], and eight predominate forms the Terpene Super Classes: myrcene (14), terpinolene (15), ocimene (16), limonene (17), α-pinene (18), humulene (19), linalool (20), and β-caryophyllene (21) ( Figure 5). ...
... A hypothesis of a synergistic effect between cannabinoids and terpenes has been postulated given the so-called entourage effect [34]. To date, no reliable scientific evidence of this synergy exists, at least at the cannabinoid receptor level [88]. ...
This study explores the complementary or synergistic effects of medicinal cannabis constituents, particularly terpenes, concerning their therapeutic potential, known as the entourage effect. A systematic review of the literature on cannabis “entourage effects” was conducted using the PRISMA model. Two research questions directed the review: (1) What are the physiological effects of terpenes and terpenoids found in cannabis? (2) What are the proven “entourage effects” of terpenes in cannabis? The initial approach involved an exploratory search in electronic databases using predefined keywords and Boolean phrases across PubMed/MEDLINE, Web of Science, and EBSCO databases using Medical Subject Headings (MeSH). Analysis of published studies shows no evidence of neuroprotective or anti-aggregatory effects of α-pinene and β-pinene against β-amyloid-mediated toxicity; however, modest lipid peroxidation inhibition by α-pinene, β pinene, and terpinolene may contribute to the multifaceted neuroprotection properties of these C. sativa L. prevalent monoterpenes and the triterpene friedelin. Myrcene demonstrated anti-inflammatory proprieties topically; however, in combination with CBD, it did not show significant additional differences. Exploratory evidence suggests various therapeutic benefits of terpenes, such as myrcene for relaxation; linalool as a sleep aid and to relieve exhaustion and mental stress; D-limonene as an analgesic; caryophyllene for cold tolerance and analgesia; valencene for cartilage protection; borneol for antinociceptive and anticonvulsant potential; and eucalyptol for muscle pain. While exploratory research suggests terpenes as influencers in the therapeutic benefits of cannabinoids, the potential for synergistic or additive enhancement of cannabinoid efficacy by terpenes remains unproven. Further clinical trials are needed to confirm any terpenes “entourage effects.”
... The leaves are green and palmate synergistically with some cannabinoids, producing antipr fects. Among flavonoids, cannavaflavin A has also been p tory [4]. ...
... Within cannabinoids, tetrahydrocannabinol (THC) is teristic chemical compound of the plant, together with CB mechanisms CB1 (greater affinity than CB2) and CB2, w sedation, appetite, and mood, in addition to being a bronc oxidant, and anti-inflammatory. It is considered the most nent of the plant [4]. ...
... AEA is degraded by fatty acid amide hydrolase (FAAH), and 2-AG by monoacylglycerol lipase (MAGL). The CB receptors are the CB1 receptor, found in the brain and the central nervous system, and the CB2 receptor, which is located in the cells of the immune system and in peripheral organs regulating other types of processes [4,10]. Besides the pharmacodynamic parameters, bioavailability is an important parameter of a drug's understanding. ...
Background/Objectives: Cannabis sativa L. is a plant that has been used for thousands of years for its industrial and medicinal properties. In recent years, there has been a rise in the study of this plant due to its bioactive compounds for pharmaceutical applications. Particularly, cannabidiol has demonstrated analgesic and non-psychoactive properties. The objective of this systematic review is to update and to gather the clinical and preclinical evidence on CBD in pain treatment. Methods: This study was performed following the PRISMA guidelines and using the following search terms “((cannabidiol) NOT (THC)) NOT (tetrahydrocannabinol)) AND (pain treatment)” in PubMed and Web of Science, with the following inclusion criteria: CBD pain treatment without THC in monotherapy, including both clinical and preclinical trials. From the initial sample of more than 500 articles, a total of 40 studies were selected, eliminating duplicate studies from the databases and considering the inclusion and exclusion criteria. On one hand, clinical trials were analyzed using CBD products without THC used in monotherapy, assigning a Jadad score to evaluate the quality/bias of the trials; on the other hand, the main preclinical trials were analyzed, grouping the results into in vivo and in vitro trials. Results: Based on the review conducted, there is sufficient clinical and preclinical evidence of CBD in pain treatment, so CBD could be an effective and safe treatment in reducing pain due to its analgesic and anti-inflammatory properties. These effects appear to be primarily mediated by the activation of TRPV-1, 5HT-1A, and CB1, with emerging therapeutic relevance in the management of osteoarthritis and chronic pain. Conclusions: Although clinical and preclinical research show promising results, clinical evidence is limited, and more studies should be performed in the future with isolated CBD.
... 48 THC is responsible for most of the therapeutical and adverse effects of cannabis, including its psychostimulant properties, whereas CBD lacks psychostimulant effect. 48,49 Extreme caution is warranted when administering cannabis-based products to patients with specific genetic predispositions or psychiatric disorders such as psychosis, bipolar disorder, panic syndrome, anxiety, phobias, paranoia, abnormal liver or kidney function, amotivational syndrome of adolescence, and schizophrenia. 50 Common adverse effects associated with THC include anxiety, panic syndrome, drowsiness, dry mouth, euphoria, hilarity, relaxation, and abnormal perception of distances. ...
... 48,51,52 Conversely, CBD could increase serum concentrations of haloperidol, antipsychotics, tricyclic antidepressants, calcium channel blockers, atorvastatin and simvastatin, beta-blockers, antihistamines, antiretrovirals, opioids, clobazam, macrolides, sildenafil, cyclosporine, tamoxifen, and warfarin. 49,59,52 Most reported pharmacological interactions are associated with the concomitant use of CNS depressants, such as alcohol and benzodiazepines. Pimozide stands as an absolute contraindication for concurrent use with medicinal cannabis due to an increased risk of QT interval widening (Supplementary Material). ...
... On the other hand, camphene is a widespread natural product found in Liquidamar species, Chrysanthetbmum, Zingiber officinale, and Rosmarinus offinialis [13]. Camphene can be used as a pyrogen for the production of nano/macroporous polycaprolactone for injectable cell delivery [51], and as starting material for the production of isoborneol derivatives [52,53]. Borneol and isoborneol Figure 2. Main isomerization products of α-pinene and β-pinene: (1) camphene, (2) tricyclene (3) α-fenchene (4) bornylene (5) limonene (6) terpinene (7) β-phellandrene (8) p-cymene. ...
... This lack of selectivity represents a significant drawback of these materials for this application. Terpinolene, a cyclic monoterpene, is a common constituent of certain commercial cannabis chemovars [51,74] and is a distinguishing feature of "sativa" strains [75]. This compound has demonstrated the ability to inhibit LDL oxidation, which holds significance in the treatment of atherogenesis and coronary artery disease [76]. ...
Monoterpenes derived from various biomass constitute an important platform for synthesizing fragrances, intermediates, and pharmaceuticals. In this review, the most recent and relevant transformations of terpenes are discussed with the primary focus on heterogeneous catalysis emphasizing green chemistry and green chemical engineering aspects. This review aims to outline significant recent advancements in the transformations of terpenes of particular importance for academic and industrial research. This is accomplished by highlighting the most pivotal reactions, including oxidation, epoxidation, hydroformylation, CO2 cycloaddition, isomerization, condensation, and one-pot synthesis (such as tandem and telescopic reactions), using heterogeneous catalytic routes that have been published in the literature in the last decade. The review provides insights on the catalyst design for the transformations mentioned above tailoring selectivity and highlights the structure–activity relationship.
... The cannabinoids interact with the body's endocannabinoid system, influencing various physiological processes [6,7]. The most studied cannabinoids are (−)-∆9-trans-tetrahydrocannabinol (THC) and cannabidiol (CBD) [8]. THC is known for its psychoactive effects but also provides medicinal benefits such as reducing chronic pain, stimulating appetite, and proving beneficial in conditions like Alzheimer's disease and cancer [2,9]. ...
... THC is known for its psychoactive effects but also provides medicinal benefits such as reducing chronic pain, stimulating appetite, and proving beneficial in conditions like Alzheimer's disease and cancer [2,9]. CBD, a non-psychoactive cannabinoid, is recognized for its anti-inflammatory, anxiolytic, and antiepileptic properties [8][9][10]. Terpenes, the volatile aromatic compounds found in the inflorescence of medicinal cannabis, play a pivotal role in enhancing cannabis therapeutic efficacy and consumer experience [9,11]. ...
A limited number of studies have examined how drying conditions affect the cannabinoid and terpene content in cannabis inflorescences. In the present study, we evaluated the potential of controlled atmosphere drying chambers for drying medicinal cannabis inflorescence. Controlled atmosphere drying chambers were found to reduce the drying and curing time by at least 60% compared to traditional drying methods, while preserving the volatile terpene content. On the other hand, inflorescences subjected to traditional drying were highly infested by Alternaria alternata and also revealed low infestation of Botrytis cinerea. In the high-THC chemovar ("240"), controlled N 2 and atm drying conditions preserved THCA concentration as compared to the initial time point (t 0). On the other hand, in the hybrid chemovar ("Gen12") all of the employed drying conditions preserved THCA and CBDA content. The optimal drying conditions for preserving monoterpenes and sesquiterpenes in both chemovars were C5O5 (5% CO 2 , 5% O 2 , and 90% N 2) and pure N 2 , respectively. The results of this study suggest that each chemovar may require tailored drying conditions in order to preserve specific terpenes and cannabinoids. Controlled atmosphere drying chambers could offer a cost-effective, fast, and efficient drying method for preserving cannabinoids and terpenes during the drying process while reducing the risk of mold growth.
... The terpene and terpenoid profiles can be associated with the geographical origin of the Cannabis plant or product [9,10] and to specific strains, which have been developed with distinct aromas and flavors [11]. It has been reported that some terpenes possess antimicrobial, antiinflammatory, immuno-modulatory, anticancer and anti-anxiety properties [12][13][14][15], but they are best recognized for their flavor and aroma, which contribute to consumer preferences (e.g., essential oils and food flavoring) [16]. This explains the choice of Cannabis for recreational use by consumers and the possible synergistic effects of cannabinoids and terpenes with regard to medical benefits [17][18][19]. ...
... Finally, Figure 7 shows the trend in the amount of the main terpenes in our samples, whose principal bioactivity (e.g., anti-inflammatory, sedative, analgesic, antimicrobial, anticancer, or antioxidant) is reported in the literature [12]. Considering the fact that in the oil used as a solvent, the volatile components collected during decarboxylation undergo a dilution step, the final inflorescence extracts showed a comparable relative distribution, with the influence of F1 clearly predominant. ...
The development of selective extraction protocols for Cannabis-inflorescence constituents is still a significant challenge. The characteristic Cannabis fragrance can be mainly ascribed to monoterpenes, sesquiterpenes and oxygenated terpenoids. This work investigates the entrapment of Cannabis terpenes in olive oil from inflorescences via stripping under mild vacuum during the rapid microwave-assisted decarboxylation of cannabinoids (MW, 120 °C, 30 min) and after subsequent extraction of cannabinoids (60 and 100 °C). The profiles of the volatiles collected in the oil samples before and after the extraction step were evaluated using static headspace solid-phase microextraction (HS-SPME), followed by gas chromatography coupled to mass spectrometry (GC-MS). Between the three fractions obtained, the first shows the highest volatile content (~37,400 mg/kg oil), with α-pinene, β-pinene, β-myrcene, limonene and trans-β-caryophyllene as the main components. The MW-assisted extraction at 60 and 100 °C of inflorescences using the collected oil fractions allowed an increase of 70% and 86% of total terpene content, respectively. Considering the initial terpene amount of 91,324.7 ± 2774.4 mg/kg dry inflorescences, the percentage of recovery after decarboxylation was close to 58% (mainly monoterpenes), while it reached nearly 100% (including sesquiterpenes) after extraction. The selective and efficient extraction of volatile compounds, while avoiding direct contact between the matrix and extraction solvents, paves the way for specific applications in various aromatic plants. In this context, aromatized extracts can be employed to create innovative Cannabis-based products within the hemp processing industry, as well as in perfumery, cosmetics, dietary supplements, food, and the pharmaceutical industry.
... Linalool is a noncyclic monoterpenoid and a major component in the essential oils of various aromatic plants traditionally used as sedatives (Elisabetsky, 2002). Linalool has also been established to have sedative, antidepressant, anxiolytic, and immune potentiating effects (Russo & Marcu, 2017). This can be supported by the study of Xu et al. (2021) wherein mice and rats treated with linalool at Shenque, an acupoint located in the umbilicus and connected with the meridians, had improved sleep rate, reduced sleep latency, and prolonged sleep duration. ...
... Запах оцимену складний, характеризується як квітково-лимонний. У медичній ботаніці відомі протисудомні властивості рослин, які містять значну кількість оцимену (Russo et al., 2017 Біологія. Фармація показники ще тільки вивчаються. ...
... C. sativa biosynthesizes various specialized metabolites, mainly in glandular trichomes, where cannabinoids and terpenes are accumulated [3,4]. Although research has mainly focused on metabolites from glandular trichomes for their therapeutic properties [5], other parts of the hemp plant are also valuable sources of specialized metabolites. Indeed, monoterpenes and diterpenes have been reported in inflorescences, while sesquiterpenes, triterpenes, alkaloids, and phytosterols have been described in roots and flavonoids in the leaves [6]. ...
Cannabis sativa L., specifically hemp, is a traditional herbaceous plant with industrial and medicinal uses. While much research has focused on cannabinoids and terpenes, the potential of hemp roots is less explored due to bioproduction challenges. Still, this material is rich in bioactive compounds and demonstrates promising anti-inflammatory, antimicrobial, and antioxidant properties. Biotechnological methods, such as hairy root cultures, enable the efficient production of specialized metabolites while avoiding the issues of outdoors cultures. Despite these benefits, the chemical diversity understanding of hemp hairy roots remains limited. In this study, we conducted an extensive NMR and LC/MS chemical profiling of hemp hairy roots to determine their chemical composition, revealing the presence of cannabisins for the first time. We then investigated the accumulation of cannabisins and triterpenes in both hemp hairy roots and hemp aeroponic roots. Our findings reveal that hairy roots produce 12 times more cannabisins and 6 times more triterpenes than aeroponic roots, respectively, in addition to yielding 3 times more biomass in bioreactors. Preliminary bioassays also suggest antioxidant and antifungal properties. This research underscores the potential of hemp hairy roots as a valuable source of specialized metabolites and calls for further exploration into their bioactive compounds and applications.
... These occur through the binding and activation of CB1 receptors, which are predominantly present in the central nervous system (Pertwee, 2008). CBD, although sharing with Δ9-THC a similar chemical structure, does not induce psychomimetic effects because of its lower affinity for the central CB1 receptors (Russo & Marcu, 2017). ...
... Among 30 compounds identified in the leaves of M. koenigii, molecules such as caryophyllene oxide and α-terpineol have shown an increase in concentration in NADES-AHD as compared to HD. Caryophyllene oxide is known to be non-sensitising and nontoxic. It is known to have anticholinesterase, analgesic, anti-inflammatory, antifungal, and insecticidal activities (Russo and Marcu 2017;Karakaya et al. 2020). Whereas α-terpineol is known to have antihypertensive, antioxidant, insecticidal, anticonvulsant, anti-nociceptive, and anticancer potential. ...
Aphis craccivora Koch and Planococcus lilacinus Cockerell are phloem feeders and act as vectors for transmitting plant viruses to agricultural and horticultural crops thereby damaging them. The persistent and widespread use of synthetic, wide-spectrum pesticides has resulted in resistance development that is detrimental to the environment, human health, and natural enemies of pests. The present investigation uses various extraction mediums to examine the insecticidal efficacy of essential oils (EOs) isolated from Murraya koenigii (L.) leaves. Increase in yield was observed in the EO extracted using NADES-AHD [0.16% (obtained with hydro-distillation)] to 0.30% [obtained with N-1 (glycerol:lactic acid)]. EO obtained with water was found more effective against A. craccivora (LD 50 = 0.89 µL/insect) and followed by N-1 (glycerol:lactic acid), and N-3 (choline chloride:citric acid) (LD 50 = 1.29-1.38 µL/insect). Similarly, EO isolated by water and N-4 (choline chloride:oxalic acid) was effective against P. lilacinus (LD 50 = 2.63-3.06 µL/insect). Additionally, the EO prepared by water substantially reduced glutathione S-transferase (GST) and acetylcholinesterase (AChE) in target pests, suggesting that these enzymes may be the EOs' site of action. NADES-AHD has enhanced the EO yield as compared to the conventional method. The EO obtained with water showed promising toxicity against target pests and target site of action. Therefore, based on field and greenhouse bio-efficacy experiments, EOs/biopesticides/botanicals can be proposed for controlling the spread of mealy bugs and aphids.
... Their structures can vary; some of these compounds are linear carbon chains, some are branched, and others are cyclic or polycyclic. Terpenes and terpenoids are both volatile compound families and are responsible for the characteristic aroma of cannabis, with more than 200 identified molecules [3]. They also play valuable biological roles as pollinator attractants, herbivore repellents, or antibacterial agents [4]. ...
... Cannabis, in its many forms, is already being prescribed to cancer patients all over the world, mainly as a palliative treatment for the inhibition of nausea and emesis associated with chemotherapy, appetite stimulation, pain relief, and relief from insomnia (Abrams and Guzman, 2015). On top of that, recent studies have demonstrated that phytocannabinoids also possess anticancer potential (McAllister et al., 2015;Hinz and Ramer, 2022;Baram et al., 2019;Russo and Marcu, 2017;Velasco et al., 2016;Guzmán, 2003). ...
In T-cell acute lymphoblastic leukemia (T-ALL), more than 50% of cases display autoactivation of Notch1 signaling, leading to oncogenic transformation. We have previously identified a specific chemovar of Cannabis that induces apoptosis by preventing Notch1 maturation in leukemia cells. Here, we isolated three cannabinoids from this chemovar that synergistically mimic the effects of the whole extract. Two were previously known, cannabidiol (CBD) and cannabidivarin (CBDV), whereas the third cannabinoid, which we termed 331-18A, was identified and fully characterized in this study. We demonstrated that these cannabinoids act through cannabinoid receptor type 2 and TRPV1 to activate the integrated stress response pathway by depleting intracellular Ca ²⁺ . This is followed by increased mRNA and protein expression of ATF4, CHOP, and CHAC1, which is hindered by inhibiting the upstream initiation factor eIF2α. The increased abundance of CHAC1 prevents Notch1 maturation, thereby reducing the levels of the active Notch1 intracellular domain, and consequently decreasing cell viability and increasing apoptosis. Treatment with the three isolated molecules resulted in reduced tumor size and weight in vivo and slowed leukemia progression in mice models. Altogether, this study elucidated the mechanism of action of three distinct cannabinoids in modulating the Notch1 pathway, and constitutes an important step in the establishment of a new therapy for treating NOTCH1 -mutated diseases and cancers such as T-ALL.
... Hemp-type Cannabis not only features high stem elongation rates and very active cell wall metabolism to produce strong bast fibres, but has also been selected for its seed oil rich in polyunsaturated fatty acids, and for its persistence on marginal lands with low nitrogen input (Struik et al., 2000;Tang et al., 2017). In addition, hemp-type cultivars can contain high levels of CBD, which is recognized for its non-intoxicating pharmacological properties (Russo and Marcu, 2017). The ability of hemp roots to forage for scarce nutrients make it highly nutrient efficient, while its capacity to exclude or redistribute certain soil contaminants, such as heavy metals and sodium, away from growing organs has also fostered its use in phytoremediation (Linger et al., 2002;Husain et al., 2019;Adesina et al., 2020). ...
Cannabis sativa L., one of humanity’s oldest cultivated crops, has a complex domestication history due to its diverse uses for fibre, seed, oil and drugs, and its wide geographic distribution. This review explores how human selection has shaped the biology of hemp and drug-type Cannabis, focusing on acquisition and utilisation of nitrogen and phosphorus, and how resulting changes in source-sink relations shape their contrasting phenology. Hemp has been optimized for rapid, slender growth and nutrient efficiency, whereas drug-type cultivars have been selected for compact growth with large phytocannabinoid producing female inflorescences. Understanding these nutrient use and ontogenetic differences will enhance our general understanding of resource allocation in plants. Knowledge gained in comparison with other model species, such as tomato, rice or Arabidopsis thaliana can help inform crop improvement and sustainability in the Cannabis industry.
... the evaluation of their biological and pharmaceutical potential. 23 Furthermore, the multiple compounds produced by the C. sativa plant, including cannabinoids, flavonoids, and terpenoids-comprising up to 3.5% of monoterpenoids and sesquiterpenoids in dry flowers 24 -have been suggested to function as polypharmaceutical agents by modulating each other's activity, acting on multiple targets, 25-27 synergizing with the therapeutic effects of Δ 9 -THC, and mitigating its side effects. 25,28,29 Whole C. sativa extracts have been shown to be more potent 30 and less toxic 31 than pure Δ 9 -THC. ...
Introduction
Cannabis sativa is a highly versatile plant with a long history of cultivation and domestication. It produces multiple compounds that exert distinct and valuable therapeutic effects by modulating diverse biological systems, including the endocannabinoid system (ECS). Access to standardized, metabolically diverse, and reproducible C. sativa chemotypes and chemovars is essential for physicians to optimize individualized patient treatment and for industries to conduct drug‐discovery campaigns.
Objective
This study aimed to characterize and assess the phytochemical diversity of C. sativa chemotypes in diverse ecological regions of Colombia, South America.
Methodology
Ten cannabinoids and 23 terpenes were measured using liquid and gas chromatography, in addition to other phenotypic traits, in 156 C. sativa plants that were grown in diverse ecological regions in Colombia, a hotspot for global biodiversity.
Results
Our results reveal significant phytochemical diversity in Colombian‐grown C. sativa plants, with four distinct chemotypes based on cannabinoid profile. The significant amount of usually uncommon terpenes suggests that Colombia's environments may have unique capabilities that allow the plant to express these compounds. Colombia's diverse climates offer enormous cultivation potential, making it a key player in both domestic and international medicinal and recreational C. sativa trade.
Conclusion
These findings underscore Colombia's capacity to pioneer global C. sativa production diversification, particularly in South America with new emerging markets.
... 3 A previous study revealed that CRs contain diverse chemical compounds, with triterpenoids being the most prominent due to their crucial biological roles. 4 Key triterpenoids include friedelin and epifriedelanol ( Figure 1 A and B), 5 which exhibit various biological properties. 6 Pressurized extraction technologies, classified as green extraction, avoid harmful organic solvents and are increasingly favored for extracting plant materials and other natural products. ...
... Many of the main terpene compounds of hemp EO have been reported to induce antidepressant, relaxing, anxiolytic, sedative but also antimicrobial, antioxidant and anticancer effects [15,16]. ...
Cannabis sativa L. is a plant that has been cultivated since ancient times thanks to its various uses. Even its extraction products, such as essential oil and hydrolate, having a varied chemical composition and rich in bioactive components, find wide use in different sectors, gathering ever-increasing interest over time. In this work, the essential oil of Cannabis sativa L. cv. Carmagnola was characterized by using Gas Chromatography/Mass Spectrometry (GC/MS) and, for the first time, the chemical profile of the hydrolate was also described through different analytical techniques such as Large-Volume Injection Gas Chromatography/Mass Spectrometry (LVI-GC/MS) and Direct Immersion-Solid Phase Microextraction-Gas Chromatography/Mass spectrometry (DI-SPME-GC/MS), in order to provide a more complete compositional profile. The results of the analyses conducted on the hydrolate highlighted a high content of α-terpineol; on the other side, in the essential oil, a prevalence of monoterpenes, with α-pinene and limonene as the characterizing components, was detected. Both matrices were also investigated to evaluate their cytotoxic activity by using a panel of cancer cell lines derived from different histotypes such as melanoma (A375, LOX IMVI), non-small cell lung cancer (H1299, A549), colon (HT29) and pancreatic (L3.6) cancer cell lines. The obtained data demonstrated that essential oil was more effective than hydrolate in terms of reduction in cell viability.
... As a crop, Cannabis sativa can be grown for its fiber (Del Gatto Andrea et al., 1999;Johnson, 2014) or for its seeds (Callaway, 2004;Hanks, 2008). The hemp leaves and flowers have a specific aroma, and their extracts contain a variety of useful terpenes and flavonoids, as well as other compounds that are used as pesticides (insecticides, fungicides, herbicides) or effective therapeutic agents (Kolodziejczyk et al., 2012;Băluţă, 2013;Russo & Marcu, 2017). ...
This work aims to present data related to the structure of the entomofauna and the variation of the relative abundance of species in the ecosystem of the monoecious hemp crop, cultivated in an ecological system. The researches were carried out between 2017 and 2018, in monoecious hemp crop, cultivated in an ecological system, within the Agricultural Research and Development Station Secuieni-Neamț. The biological material was collected by the classic method, namely with the help of Barber-type soil traps, which were installed in the monoecious hemp crop. Later, the collected material was subjected to a mathematical analysis, as a result of which a series of ecological indicators were obtained, highlighting the characteristics of the analyzed biocenosis. 423 specimens were collected, belonging to 4 orders, 11 families, 12 subfamilies, 13 genera and 15 species. The order Coleoptera had the maximum weight by the number of specimens collected (48.70%), while the order Lepidoptera recorded a weight of only 0.24%. The Gryllidae family had the maximum weight by the number of specimens collected (36.88%), while the Noctuidae and Scutelleridae families have 0.24% each.
... 34 Finally, the limonene present in EOSO could also contribute to the antibacterial effect observed insofar as it has demonstrated significant antibiotic effects against S. aureus and S. pyogenes. 35 The mechanism of action of EOSO needs further investigation. Nevertheless, it is active on both Gram-positive and Gram-negative bacteria with different cell wall structures. ...
Solenostemma oleifolium is a tropical plant growing in the Algerian desert that is traditionally used to treat several illnesses, including infection. We investigate essential oil components from leaves of Solenostemma oleifolium (EOSO) and its antibacterial activity. Using Gas Chromatography and Mass Spectrometry (GC-MS), twenty compounds were identified in EOSO, including linalool (57.10%), terpineol (12.95%), trans-geraniol (12.65%), and nerol (4.67%). Nuclear magnetic resonance (NMR) analysis allowed us to confirm linalool as the main component of EOSO. Antibacterial activity was tested by agar diffusion and microdilution methods for minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). For EOSO, the inhibition diameters ranged from 16.79 to 39.84 mm, the MIC ranged from 1.066 to 8.54 mg mL-1 and the MBC ranged from 20 to 100 mg mL-1. For linanool, the inhibition diameters ranged from 11.1 to 31.87 mm, the MIC ranged from 2.68 to 14.3 mg mL-1 and, the MBC ranged from 40 to 100 mg mL-1.EOSO and linalool exhibited significant antibacterial activity against all the tested bacteria. This study confirmed the antibacterial activity of the S. oleifolium essential oil and that linalool is the principal constituent of the EOSO.
... However, there are far more chemical constituents in Cannabis than THC and CBD. There are over 550 unique chemical compounds in Cannabis, many of which are bioactive and contribute to its overall effect (Russo and Marcu, 2017;Mudge et al., 2019;Rock and Parker, 2021). Different chemovars of Cannabis elicit varying intensities of behavioral outcomes (Devsi et al., 2020), underlining the need to understand the pharmaceutical effects of the different constituents of the whole plant. ...
Chronic pain conditions affect nearly 20% of the population in the United States. Current medical interventions, such as opioid drugs, are effective at relieving pain but are accompanied by many undesirable side effects. This is one reason increased numbers of chronic pain patients have been turning to Cannabis for pain management. Cannabis contains many bioactive chemical compounds; however, current research looking into lesser-studied minor cannabinoids in Cannabis lacks uniformity between experimental groups and/or excludes female mice from investigation. This makes it challenging to draw conclusions between experiments done with different minor cannabinoid compounds between labs or parse out potential sex differences that could be present. We chose five minor cannabinoids found in lower quantities within Cannabis: cannabinol (CBN), cannabidivarin (CBDV), cannabigerol (CBG), Δ8-tetrahydrocannabinol (Δ8-THC), and Δ9-tetrahydrocannabivarin (THCV). These compounds were then tested for their cannabimimetic and pain-relieving behaviors in a cannabinoid tetrad assay and a chemotherapy-induced peripheral neuropathy (CIPN) pain model in male and female CD-1 mice. We found that the minor cannabinoids we tested differed in the cannabimimetic behaviors evoked, as well as the extent. We found that CBN, CBG, and high dose Δ8-THC evoked some tetrad behaviors in both sexes, while THCV and low dose Δ8-THC exhibited cannabimimetic tetrad behaviors only in females. Only CBN efficaciously relieved CIPN pain, which contrasts with reports from other researchers. Together these findings provide further clarity to the pharmacology of minor cannabinoids and suggest further investigation into their mechanism and therapeutic potential. Significance Statement Minor cannabinoids are poorly studied ligands present in lower levels in Cannabis than cannabinoids like THC. In this study we evaluated 5 minor cannabinoids (CBN, CBDV, CBG, THCV, and Δ8-THC) for their cannabimimetic and analgesic effects in mice. We found that 4 of the 5 minor cannabinoids showed cannabimimetic activity, while one was efficacious in relieving chronic neuropathic pain. This work is important in further evaluating the activity of these drugs, which are seeing wider public use with marijuana legalization.
... Cannabis plants have been selectively bred over time to contain greater concentrations of THC, and it is now common for cannabis flower sold in dispensaries to contain upwards of 20-30% THC (Cash et al., 2020;Freeman et al., 2021;Vergara et al., 2017). Beyond THC, the cannabis plant contains hundreds of additional constituents, including cannabidiol or CBD, so-called "minor" cannabinoids (e.g., cannabigerol or CBG, THCV, etc.), and terpenoids or "terpenes" (e.g., D-limonene, pinene, beta-caryophyllene; Hazekamp et al., 2016;Vergara et al., 2017;Russo and Marcu, 2017). ...
... [2]. Based on this data, it seems unlikely that the type of MC (sativa, indica, or hybrid) or the terpene profile influences effectiveness since in general, β-myrcene is the most prevalent terpene in MC [26]. Similarly, it seems to be unlikely that taste and smell had a relevant impact, since most of the participants rated taste and smell as good or very good. ...
Background Up to now, it is unclear whether different medicinal cannabis (MC) strains are differently efficacious across different medical conditions. In this study, the effectiveness of different MC strains was compared depending on the disease to be treated.
Methods This was an online survey conducted in Germany between June 2020 and August 2020. Patients were allowed to participate only if they received a cannabis-based treatment from pharmacies in the form of cannabis flowers prescribed by a physician.
Results The survey was completed by n=1,028 participants. Most participants (58%) have used MC for more than 1 year, on average, 5.9 different strains. Bedrocan (pure tetrahydrocannabinol to pure cannabidiol [THC:CBD]=22:<1) was the most frequently prescribed strain, followed by Bakerstreet (THC:CBD=19:<1) and Pedanios 22/1 (THC:CBD=22:1). The most frequent conditions MC was prescribed for were different pain disorders, psychiatric and neurological diseases, and gastrointestinal symptoms. Overall, the mean patient-reported effectiveness was 80.1% (range, 0–100%). A regression model revealed no association between the patient-reported effectiveness and the variety. Furthermore, no influence of the disease on the choice of the MC strain was detected. On average, 2.1 side effects were reported (most commonly dry mouth (19.5%), increased appetite (17.1%), and tiredness (13.0%)). However, 29% of participants did not report any side effects. Only 398 participants (38.7%) indicated that costs for MC were covered by their health insurance.
Conclusions Patients self-reported very good efficacy and tolerability of MC. There was no evidence suggesting that specific MC strains are superior depending on the disease to be treated.
... Caryophyllene oxide is a sesquiterpene that is used in cosmetics, medicines, as a preservative in the food industry and in the training of drug detection dogs. It has anti-fungal, insecticidal and anti-platelet properties 28 . (E, E)-2,4-decadienal is an aromatic substance that is used in the perfumery industry and in the food industry as a flavoring, but due to its possible carcinogenicity, its use has terms and restrictions 29 . ...
Sumac (Rhus coriaria L.) is one of the medicinal plants of Anacardiaceae family and widely used as a spice in Iran and Arab countries. Rhus coriaria var. zebaria is a small tree or large shrub, wildly growing in Iraq and described as a new variety with special characteristics. These increase the importance of studying sumac in these areas. Here, the phytochemical variations and the antibacterial activity of 50 accessions of this variety from five different climatic conditions was evaluated in order to identify the best accession to use and the best area for its cultivation. This is the most comprehensive study on this plant. Essential oil compounds were identified using GC–MS method and according to the results, Z, E-2,13-octadecadien, caryophyllene oxide, 2,4-decadienal, E-caryophyllene and nonanoic acid were among the main compounds. Also, the variety is a rich source of minerals including K, Ca, Mg, Na, P, and N. Sumac fruit extract from Akre Xerds had the highest anthocyanin and the lowest amount was from Kavilca region. The radical scavenging effect of extract from Dostic area in the concentration of 400 µg/mL is closer to the effect of ascorbic acid. The largest inhibition was found in the sumac extracted oil of Xasto Zhere area against S. aureus in compared with penicillin and amoxicillin and enrofloxacin antibiotics.
Breast cancer is the most often diagnosed malignancy worldwide and the leading cause of cancer-related deaths in women. Chemotherapeutic resistance may hinder the efficacy of therapies for breast cancer, therefore finding novel therapeutic approaches is crucial. Terpenoids are widely distributed throughout the kingdom of plants and constitute a vast array of secondary metabolites mostly composed of isoprenoid components. Terpenoids are known to have a wide spectrum of biological features. Based on the structure, terpenoids are divided into six classes. Potent natural terpenoids have been widely acknowledged as key components of contemporary breast cancer pharmacotherapy. Several compounds within this class hold promise as viable agents against breast cancer. These substances now hold promise as therapeutic agents due to significant advancements in the elucidation of the precise mechanism behind their anticancer effect. Therefore, this chapter aims to present a current summary of the most recent advances in terpenoids' potential benefits against breast cancer. Furthermore, this review offers recommendations for the development of specific terpenoids as possible medicines for breast cancer in the future.
Chronic pain represents a complex and debilitating condition that affects millions of people worldwide, significantly compromising their quality of life. The conventional approach to treating this type of pain often relies on the use of opioid analgesics and anti-inflammatory drugs. While these agents are effective in the short term, they present several limitations, including the risk of dependence, severe side effects, and, in some cases, ineffectiveness in reducing pain. In this context, medical cannabis has emerged as a promising therapeutic alternative, given its potential ability to relieve pain effectively with a favorable safety profile. This work aims to provide a comprehensive and up-to-date review of the existing literature on the effects of medical cannabis in the treatment of chronic pain. Cannabis sativa contains several pharmacologically active compounds, the most prominent of which are delta-9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), which interact with the body’s endocannabinoid system, thereby modulating the pain response. Clinical evidence has shown that cannabinoids can significantly reduce the intensity of chronic pain, particularly in cases of neuropathy, multiple sclerosis, arthritis, and other painful conditions that are unresponsive to conventional treatments. However, the full integration of medical cannabis into clinical practice faces significant obstacles, including the need for standardized dosing, long-term safety data, and regulatory frameworks. These issues, alongside concerns over adverse effects and drug interactions, must be addressed to unlock the full therapeutic potential of cannabinoids, particularly for chronic pain patients, who endure both physical suffering and the added burden of stress.
Background
Phytochemicals have long remained an essential component of the traditional medicine system worldwide. Advancement of research in phytochemicals has led to the identification of novel constituents and metabolites from phytochemicals, performing various vital functions ranging from antimicrobial properties to anticarcinogenic roles. This plant is traditionally used by local people to manage inflammation. In this study, we aim to extract and chemically profile the essential oil from the leaves of Cleistocalyx operculatus (Roxb.) Merr. & Perry and study of the anti-inflammatory and anti-proliferative role of essential oil.
Methods
The hydro distillation method was used for the extraction of essential oil, and the GC-MS was applied for the chemical profiling. The percentage of cell viability was calculated using a crystal violet assay, colony formation assay was performed using Semiquantitative PCR, Propodium iodite staining was used for cell death assay, and Western blotting was used to determine antibodies and proteins. Schrodinger 2015 software was used for molecular docking.
Results
Myrcene, a monoterpene, constitutes 56% of the oil and could be attributed to its anti-inflammatory potential. Treatment of LPS-challenged mouse macrophages RAW264.7 cells with essential oil resulted in a decline in the inflammatory markers, such as IL-1β, TNFα, iNOS, COX-2, and NFκB. Further, essential oil inhibited cancer PC-3, A431, A549, and MCF-7 cell lines at concentrations lower than normal PNT2 and HEK-293 cell lines. This decline in proliferative potential can be attributed to a decline in anti-apoptotic proteins, such as procaspase 3 and PARP, an increase in CKIs, such as p21, and a decline in the Akt signaling responsible for survival.
Conclusion
The essential oil of the plant Cleistocalyx operculatus may be a potential lead for anti-inflammatory and anti-proliferative function.
This study explores the complementary or synergistic effects of medicinal cannabis constituents, particularly terpenes, concerning their therapeutic potential, known as the entourage effect. A systematic review of the literature on cannabis entourage effects was conducted using the PRISMA model. Two research questions conducted the review: (1) What are the Physiological Effects of Terpenes and Terpenoids found in Cannabis? (2) What are the proven Entourage Effects of Terpenes in Cannabis? The initial approach involved an exploratory search in electronic databases using predefined keywords and Boolean phrases across PubMed/MEDLINE, Web of Science, and EBSCO databases, using Medical Subject Headings (MeSH). Analysis of published studies shows no evidence of neuroprotective or anti-aggregatory effects of α-pinene and β-pinene against β-amyloid-mediated toxicity, however, modest lipid peroxidation inhibition by α-pinene, β pinene, and terpinolene may contribute to the multifaceted neuroprotection properties of these C. sativa-prevalent monoterpenes and their triterpene friedelin. Myrcene demonstrated anti-inflammatory proprieties topically, however, in combination with CBD did not show significant additional differences. Exploratory evidence suggests various therapeutic benefits of terpenes, such as myrcene for relaxing; linalool as sleep aid, exhaustion relief and mental stress; D-limonene as an analgesic; caryophyllene for cold tolerance and analgesia; valencene for cartilage protection, borneol for antinociceptive and anticonvulsant potential; and eucalyptol for muscle pain. While exploratory research suggests terpenes as influencers in the therapeutic benefits of cannabinoids, the potential for synergistic or additive enhancement of cannabinoid efficacy by terpenes remains unproven. Further clinical trials are needed to confirm these constituents' individual and combined effects.
Cannabis sativa L. is one of the oldest domesticated crops. Hemp-type cultivars, which predominantly produce non-intoxicating cannabidiol (CBD), have been selected for their fast growth, seed, and fibre production, while drug-type chemovars were bred for high accumulation of tetrahydrocannabinol (THC). We investigated how the generation of CBD-dominant chemovars by introgression of hemp- into drug-type Cannabis impacted plant performance. The THC-dominant chemovar showed superior sink strength, higher flower biomass and demand-driven control of nutrient uptake. By contrast, the CBD-dominant chemovar hyperaccumulated phosphate in sink organs leading to reduced carbon and nitrogen assimilation in leaves, which limited flower biomass and cannabinoid yield. RNA-seq analyses determined organ- and chemovar-specific differences in expression of genes associated with nitrate and phosphate homeostasis as well as growth-regulating transcription factors that were correlated with measured traits. Among these were genes positively selected for during Cannabis domestication encoding an inhibitor of the phosphate starvation response SPX DOMAIN GENE3, nitrate reductase and two nitrate transporters. Altered nutrient sensing, acquisition or distribution are likely a consequence of adaption to growth on marginal, low-nutrient input lands in hemp. Our data provide evidence that such ancestral traits may become detrimental for female flower development and consequently overall CBD yield in protected cropping environments.
Introduction: Cannabis cultivars were usually categorized based on their genetic profile as sativa, indica, or hybrid types. However, these three criteria do not allow sufficient differentiation between the numerous varieties of cannabis strains. Furthermore, this classification is based on morphological and bio-geographical properties of the plants and does not represent the chemical composition of different cultivars. The concentration of cannabinoids and terpenes are crucial for the pharmacological effect, not only because of the known entourage effect, and therefore needs to be considered by categorization. Materials and Methods: A total of 140 medicinal cannabis flowers available on the German market were analyzed regarding their individual terpene profile using GC-MS analysis. Statistical evaluation was performed to investigate correlations and data relations as well as for clustering. Results: Multivariate analysis showed correlations between individual terpenes. However, there was no statistical correlation between terpene profiles and their respective genetic profile. Terpene profiles of sativa, indica, and hybrid strains are quite heterogenous and clearly showed that there is no relation between terpenes and the estimated pharmacological effect. As a result, we suggest a new classification system based on individual terpene profiles to faster a comprehensive understanding of the expected medical effect. Discussion: Considering main terpenes, we established a concept of six clusters with various terpene profiles being attributed to different medicinal applications. We excluded tetrahydrocannabinol (THC) and cannabidiol (CBD) content from clustering as most of the strains were THC dominant and therefore distort the results. Our pattern of strains with similar terpene profiles might refine the existing classes of chemotypes with different THC:CBD content. Conclusion: The categorization of cannabis strains based on their terpene profiles allows a clearer, finer and, above all, more meaningful classification than the existing sativa/indica classification. Due to the entourage effect and the interactions between cannabinoids and terpenes, this group of substances is also given the necessary consideration when selecting the right medicine for the individual. Within the next steps, further studies are needed with the aim of mapping clinical validated effects to our chemovars. If it is possible to correlate therapy of symptoms to specific chemical profiles personalized cannabinoid therapy will be possible.
Cannabinoid decarboxylation via thermo‑chemical conversion has the potential to reduce the cannabinoid degrada‑tion and evaporation due to short reaction time and use of water as the solvent. When combined with pressurizedliquid extraction (PLE), thermo‑chemical conversion can be performed as the first stage in the extraction procedure.PLE utilizes a closed system at elevated temperatures and pressure to increase the solvation power, which contrib‑utes to decreased viscosity and increased diffusion rate. With this new in-extraction decarboxylation approach thereremain variables that need full understanding before up scaling from bench top to pilot or commercial scale. Herein,the thermo‑chemical decarboxylation kinetics was studied for industrial hemp via PLE at different temperatures(80–160 °C) and reaction times (1–90 min). The reaction was found to be pseudo‑first order. Model verification on CBDand CBG resulted in acceptable results; however, an anomaly in the minor cannabinoids suggests that cannabinoidconcentration may influence model kinetics
Tetrahydrocannabivarin (THCV) is a phytocannabinoid that is becoming popular across the North American cannabis market. THCV has been reported to reduce blood sugar and act as an appetite suppressant in several independent pre-clinical studies, which has earned it the popular nickname of "diet weed," despite few human studies of these effects. Additionally, THCV is usually and incorrectly categorized as an intoxicating analogue of tetrahydrocannabinol (THC), which causes confusion among both consumers and regulators. In this article, we examine what is known pre-clinically and clinically about THCV, as well as highlight mechanisms of action, in order to clarify the scientific differences between THCV and THC. THCV, although structurally similar to THC, has distinct pharmacological activity and physiological effects at the doses currently reported in the literature. We highlight areas of opportunity for further THCV research in order to determine the full and appropriate potential for unique health, wellness, and therapeutic applications of this compound.
For millennia, various cultures have utilized cannabis for food, textile fiber, ethno-medicines, and pharmacotherapy, owing to its medicinal potential and psychotropic effects. An in-depth exploration of its historical,
chemical, and therapeutic dimensions provides context for its contemporary understanding. The criminalization
of cannabis in many countries was influenced by the presence of psychoactive cannabinoids; however, scientific
advances and growing public awareness have renewed interest in cannabis-related products, especially for
medical use. Described as a ’treasure trove,’ cannabis produces a diverse array of cannabinoids and noncannabinoid compounds. Recent research focuses on cannabinoids for treating conditions such as anxiety,
depression, chronic pain, Alzheimer’s, Parkinson’s, and epilepsy. Additionally, secondary metabolites like
phenolic compounds, terpenes, and terpenoids are increasingly recognized for their therapeutic effects and their
synergistic role with cannabinoids. These compounds show potential in treating neuro and non-neuro disorders,
and studies suggest their promise as antitumoral agents. This comprehensive review integrates historical,
chemical, and therapeutic perspectives on cannabis, highlighting contemporary research and its vast potential in
medicine.
Pain, a complex and debilitating condition affecting millions globally, is a significant concern, especially in the context of post-operative recovery. This comprehensive review explores the complexity of pain and its global impact, emphasizing the modulation of voltage-gated sodium channels (VGSC or NaV channels) as a promising avenue for pain management with the aim of reducing reliance on opioids. The article delves into the role of specific NaV isoforms, particularly NaV 1.7, NaV 1.8, and NaV 1.9, in pain process and discusses the development of sodium channel blockers to target these isoforms precisely. Traditional local anesthetics and selective NaV isoform inhibitors, despite showing varying efficacy in pain management, face challenges in systemic distribution and potential side effects. The review highlights the potential of nanomedicine in improving the delivery of local anesthetics, toxins and selective NaV isoform inhibitors for a targeted and sustained release at the site of pain. This innovative strategy seeks to improve drug bioavailability, minimize systemic exposure, and optimize therapeutic outcomes, holding significant promise for secure pain management and enhancing the quality of life for individuals recovering from surgical procedures or suffering from chronic pain.
Hemp (Cannabis sativa L.) has been used for millennia as a rich source of food and fibers, whereas hemp flowers have only recently gained an increased market interest due to the presence of cannabinoids and volatile terpenes. Currently, the hemp flower processing industry predominantly focuses on either cannabinoid or terpene extraction. In an attempt to maximize the valorization of hemp flowers, the current study aimed to evaluate the phytochemical composition and antimicrobial properties of several extracts obtained from post-distillation by-products (e.g., spent material, residual distillation water) in comparison to the essential oil and total extract obtained from unprocessed hemp flowers. A terpene analysis of the essential oil revealed 14 monoterpenes and 35 sesquiterpenes. The cannabinoid profiling of extracts showed seven acidic precursors and 14 neutral derivatives, with cannabidiol (CBD) reaching the highest concentration (up to 16 wt.%) in the spent material extract. The antimicrobial assessment of hemp EO, cannabinoid-containing extracts, and single compounds (i.e., CBD, cannabigerol, cannabinol, and cannabichromene) against a panel of 20 microbial strains demonstrated significant inhibitory activities against Gram-positive bacteria, Helicobacter pylori, and Trichophyton species. In conclusion, this work suggests promising opportunities to use cannabinoid-rich materials from hemp flower processing in functional foods, cosmetics, and pharmaceuticals with antimicrobial properties.
Recently, malignant neoplasms have growingly caused human morbidity and mortality. Head and neck cancer (HNC) constitutes a substantial group of malignancies occurring in various anatomical regions of the head and neck, including lips, mouth, throat, larynx, nose, sinuses, oropharynx, hypopharynx, nasopharynx, and salivary glands. The present study addresses the phosphoinositide 3‐kinase (PI3K)/ protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway as a possible therapeutic target in cancer therapy. Finding new multitargeting agents capable of modulating PI3K/Akt/mTOR and cross‐linked mediators could be viewed as an effective strategy in combating HNC. Recent studies have introduced phytochemicals as multitargeting agents and rich sources for finding and developing new therapeutic agents. Phytochemicals have exhibited immense anticancer effects, including targeting different stages of HNC through the modulation of several signaling pathways. Moreover, phenolic/polyphenolic compounds, alkaloids, terpenes / terpenoids , and other secondary metabolites have demonstrated promising anticancer activities because of their diverse pharmacological and biological properties like antiproliferative, antineoplastic, antioxidant, and anti‐inflammatory activities. The current review is mainly focused on new therapeutic strategies for HNC passing through the PI3K/Akt/mTOR pathway as new strategies in combating HNC.
Terminalia Catappa fruits are recognized for their use in diabetes treatment, yet the mechanism by which they inhibit diabetes-related enzymes remain largely undefined. This study aimed to elucidate the therapeutic potential and interactions of T. catappa fruit extract through in vitro and in silico approaches. The compounds from T. catappa fruit were extracted using microwave-assisted extraction techniques, followed by qualitative phytochemical screening and quantitative analysis via GC-MS. The physicochemical properties were evaluated according to the Lipinski rule and ADMET criteria. Antidiabetic analyses, both in vitro and in silico, were performed on the secondary metabolites found in T. catappa fruit, targeting α-amylase and α-glucosidase enzymes. The methanol and ethyl acetate extracts of T. catappa fruit contained alkaloids, flavonoids, saponins, steroids, and terpenoids. These extracts inhibited α-glucosidase and α-amylase in a dose-dependent manner, with the methanol extract of T. catappa showing significantly higher inhibitory activity than pure acarbose (by two- and five-fold, respectively) and the ethyl acetate extract. Furthermore, the antioxidant activity of the methanolic extract was seven times greater than that of the ethyl acetate extract. Molecular docking studies supported these findings, revealing that the ΔG values of gibberellic acid, rescinnamine, and digoxin were comparable to those of acarbose. Notably, digoxin has higher ΔG values against α-amylase than acarbose, while gibberellic acid, rescinnamine, and nerolidol showed ΔG values similar to acarbose. Gibberellic acid, unique to the methanol extract, demonstrated high ΔG values, suggesting its significant role in the extract's enhanced glucosidase and amylase inhibitory activities. This study identifies specific compounds (digitoxin, rescinnamine, gibberellic acid, and nerolidol) and proposes the potential of multi-target drugs in diabetes treatment. Understanding these phytochemical constituents and their effects on diabetes-involved enzymes could benefit individuals with type 2 diabetes, particularly those at higher risk of complications.
Effects of essential oil components obtained by hydrodistillation of Ammi genus members (Ammi majus L., Ammi visnaga L. (Lam.)), which have important chemical and active components were investigated against two important storage pests; fig borer Cadra cautella (Walker) (Lepidoptera: Pyralidae) and flour moth Ephestia kuehniella Zeller (Lepidoptera: Pyralidae). A total of 23 and 14 components were detected in A. majus and A. visnaga, respectively, and the product yield was found to be 96.05%, 82.53%. Among them, the major components for A. majus are 2 heptadecanone, benzoic acid, 2 pentadecanone while for A. visnaga they are linalol, nonadecane, carvacrol. Essential oil of A. visnaga extended the adult emergence times in E. kuehniella and C. cautella while the increase in pupation time was found statistically significant only in E. kuehniella. A. visnaga essential oil reduced the adult life span in E. kuehniella at the highest dose while a decrease was detected in both doses applied in C. cautella. Adult weight and number of eggs decreased due to the application of A. visnaga in both insects. Also, alterations were observed in the adult emergence, pupation time, and pupal period. In E. kuehniella and C. cautella, adult life spans, weights and egg production of females showed statistically significant decreases depending on the application of A. majus essential oil. The findings obtained within the scope of the current study reveal that the essential oils of A. majus and A. visnaga species have the potential to be used in the control of storage pest insects.
The aim of this study was to evaluate the effect of oral cannabidiol (CBD) administration in addition to a conventional analgesic protocol on the clinical signs of 20 horses with mild joint osteoarthritis. The horses were randomly assigned to either the control group (C group) or the cannabidiol group (CBD group). Both groups were treated with phenylbutazone for 5 days. The CBD group received 0.03 mg/kg cannabidiol in hemp oil orally once daily for 14 days in addition to phenylbutazone treatment. All subjects were monitored for clinical parameters, oxidative status and blood counts. Pain and quality of life were also assessed using the Horse Chronic Pain Scale (HCPS). The CBD group showed a significant reduction in heart rate, respiratory rate, white blood cell count and oxidative stress (malondialdehyde lipid peroxidation). A significant reduction in HCPS scores was seen in both groups. Lower scores were recorded in the CBD group (3 med; range: 2/4) than in the C group (7 med; range: 4/10). The addition of a cannabidiol-based product to an analgesic protocol was well tolerated and showed positive effects on the treated subjects, improving their quality of life and pain relief.
Citrus fruits, members of the Rutaceae family, have seen a surge in the popularity of their essential oils (EO) due to their versatile industrial applications. These EOs are primarily derived from citrus fruit peels, a practice that not only reduces waste generation but also minimizes environmental contamination. Citrus EO serves as a natural and cost-effective substitute for synthetic preservatives and flavoring agents, contributing to the pursuit of safe and wholesome food, a paramount goal in the food industry. The antimicrobial properties of key compounds such as D-limonene, linalool, α & β-pinene, sabinene, β-myrcene, α-terpineol, and other bioactive chemicals are well-documented. Moreover, these components exhibit antioxidative and potential anticancer attributes. Additionally, citrus EO-based films and coatings offer diverse applications in the realm of food packaging materials. This comprehensive review delves into a variety of extraction methods, component characterization, and recent applications of citrus essential oils across different food categories. As the demand for safe and natural food continues to grow, citrus essential oils employed as food preservatives hold a promising future. Nonetheless, further research is imperative to explore broader applications and ascertain potential allergenic and toxicological consequences, ensuring the continued advancement of this promising field.
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-myrcene, (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.
Plants have been the predominant source of medicines throughout the vast majority of human history, and remain so today outside of industrialized societies. One of the most versatile in terms of its phytochemistry is cannabis, whose investigation has led directly to the discovery of a unique and widespread homeostatic physiological regulator, the endocannabinoid system. While it had been the conventional wisdom until recently that only cannabis harbored active agents affecting the endocannabinoid system, in recent decades the search has widened and identified numerous additional plants whose components stimulate, antagonize, or modulate different aspects of this system. These include common foodstuffs, herbs, spices, and more exotic ingredients: kava, chocolate, black pepper, and many others that are examined in this review.
Mosquitoes (Diptera: Culicidae) are major vectors of important pathogens and parasites. Malaria, dengue fever, yellow fever, filariasis, schistosomiasis and Japanese encephalitis cause millions of deaths every year. Mosquito control is being challenging due to the development of pesticide resistance and negative environmental concerns. In this scenario, plants employed in traditional Asian medicine may be alternative sources of newer and effective mosquitocides. In this research, we evaluated the larvicidal activity of Kadsura heteroclita leaf essential oil (EO) and its major chemical constituents (δ-Cadinene, Calarene and δ-4-Carene) against the malaria vector Anopheles stephensi, the dengue vector Aedes aegypti and the filariasis vector Culex quinquefasciatus. The chemical composition of the EO was analyzed by gas chromatography-mass spectroscopy. GC-MS revealed that the essential oil of K. heteroclita contained 33 compounds. The major chemical components were δ-Cadinene (18.3%), Calarene (14.8%) and δ-4-Carene (12.5%). The EO had a significant toxic effect against early third-stage larvae of An. stephensi, Ae. aegypti and Cx. quinquefasciatus, with LC50 values of 102.86, 111.79 and 121.97 µg/mL. The three major constituents extracted from the K. heteroclita EO were tested individually for acute toxicity against larvae of the three mosquito vectors. δ-Cadinene, Calarene and δ-4-Carene appeared most effective against An. stephensi (LC50 = 8.23, 12.34 and 16.37 µg/mL, respectively) followed by Ae. aegypti (LC50 = 9.03, 13.33 and 17.91 µg/mL), and Cx. quinquefasciatus (LC50 = 9.86, 14.49 and 19.50 µg/mL). Overall, this study adds knowledge to develop newer and safer natural larvicides against malaria, dengue and filariasis mosquito vectors.
Aims:
Several dietary compounds that are able to induce the brown fat-like phenotype in white adipocytes have been considered for treatment of obesity due to their ability to increase energy expenditure. Here, we report that limonene induces the brown fat-like phenotype in 3T3-L1 adipocytes by increasing expression of brown adipocyte-specific genes and proteins.
Main methods:
Limonene-induced browning in white adipocytes was investigated by determining expression levels of brown fat-specific genes and proteins by real-time RT-PCR, immunoblot analysis, and immunocytochemical staining.
Key findings:
Limonene enhanced mitochondrial biogenesis, as evidenced by increased mitochondrial content and immunofluorescent intensity. Limonene also significantly elevated protein levels of HSL, PLIN, p-AMPK, p-ACC, ACO, COX4, CPT1, and CYT C, suggesting its possible role in enhancement of lipolysis and lipid catabolism. Increased expression of PRDM16, UCP1, C/EBPβ, and other brown fat-specific markers by limonene was possibly mediated by activation of β3-adnergenic receptor (β3-AR), as inhibition of β3-AR inhibited up-regulation of brown fat-specific markers. Similarly, limonene-mediated activation of ERK and up-regulation of key brown adipocyte specific markers were eliminated by treatment with ERK antagonist.
Significance:
Taken together, these results suggest that limonene induces browning of 3T3-L1 adipocytes via activation of β3-AR and the ERK signaling pathway. In conclusion, our findings suggest that limonene plays a dual modulatory role in induction of the brown adipocyte-like phenotype as well as promotion of lipid metabolism and thus may have potential therapeutic implications for treatment of obesity.
Background:
β-Caryophyllene (BCP) is natural bicyclic sesquiterpene abundantly found in essential oils from various spices, fruits and medicinal as well as ornamental plants. It is approved by United States Food and Drug Administration and European agencies as food additive, taste enhancer and flavoring agent and termed as a phytocannabinoid.
Methods:
All the available literature on BCP and its synonyms were collected through different literature databases.
Results:
BCP was found to elicit a full agonist action on cannabinoid type 2 (CB2) receptors, a G-protein coupled receptor representing important therapeutic target in several diseases. Activation of CB2 receptors notably appeared devoid of psychotropic adverse effect of cannabinoids contrary to the CB1 receptors. In addition, it activates peroxisome proliferated activator receptors (PPARs) isoforms; PPAR-α &-γ and inhibits pathways triggered by the activation of toll like receptor complex; CD14/TLR4/MD2, reduce immune-inflammatory processes and exhibit synergy with μ-opioid receptor dependent pathways. Additionally, it found as potent antagonist of homomeric nicotinic acetylcholine receptors (α7-nAChRs) and devoid of effects mediated by serotonergic and GABAergic receptors. It also modulates numerous molecular targets by altering their gene expression, signaling pathways or through direct interaction. Various pharmacological activities such as cardioprotective, hepatoprotective, gastroprotective, neuroprotective, nephroprotective, antioxidant, anti-inflammatory, antimicrobial and immune-modulator have been reported in experimental studies. It has shown potent therapeutic promise in neuropathic pain, neurodegenerative and metabolic diseases.
Conclusion:
The present review provides a comprehensive insight of pharmacological and therapeutic potential of BCP, its molecular mechanism and signaling pathways in different pathological conditions. The review also examines the possibility of its further development as a novel candidate for various pathologies considering the polypharmacological and multifaceted therapeutic properties potential along with favorable oral bioavailability, lipophilicity and physicochemical properties.
Increasing knowledge on the hallmark characteristics of cancer and tumor pharmacology has promoted the introduction of phytochemicals, such as traditional Chinese medicine (TCM) in cancer therapy, which modulate numerous molecular targets and exert anti-cancer activities. β-elemene, an active and non-toxic compound isolated from the Chinese medicinal herb Rhizoma Zedoariae, has been explored as a potent anti-cancer agent against multiple cancers in extensive clinical trials and experimental research in vivo and in vitro. β-elemene exerts therapeutic potential via modulation of core hallmark capabilities of cancer by suppressing proliferative signaling, such as MAPK and PI3K/Akt/mTOR pathway, inducing cell death, up-regulating growth suppressors, deactivating invasion and metastasis and interacting replicative immortality and attenuating angiogenesis. Recent studies have significantly improved our understanding of anti-cancer activities and underlying molecular mechanisms of this Chinese medicine. This review presents these novel findings regarding the unique properties of β-elemene as an agent for cancer treatment, with an emphasis on multi-targeting biological and molecular regulation.
Although cytotoxic chemotherapy is widely used against epithelial ovarian cancer (EOC), adverse side effects and emergence of resistance can limit its utility. Therefore, new drugs with systemic delivery platforms are urgently needed for this disease. In this study, we developed linalool-incorporated nanoparticles (LIN-NPs) as a novel anticancer agent. We prepared LIN-NPs by the self-assembly water-in-oil-in-water (w/o/w) emulsion method. LIN-NP-mediated cytotoxicity and apoptosis was assessed in EOC cells and the role of reactive oxygen species (ROS) generation as the mechanism of action was evaluated. In addition, therapeutic efficacy of LIN-NP was assessed in cell lines and patient-derived xenograft (PDX) models for EOC. LIN-NPs had significant cytotoxicity and apoptotic activity against EOC cells including A2780, HeyA8, and SKOV3ip1. LIN-NP treatment increased apoptosis in EOC cells through ROS generation and a subsequent decrease in mitochondrial membrane potential and increase in caspase-3 levels. In addition, 100 mg/kg LIN-NPs significantly decreased tumor weight in the HeyA8 (P < 0.001) and SKOV3ip1 (P = 0.006) in vivo models. Although treatment with 50 mg/kg LIN-NP did not decrease tumor weight compared to the control group, combination treatment with paclitaxel significantly decreased tumor weight compared with paclitaxel alone in SKOV3ip1 xenografts (P = 0.004) and the patient-derived xenograft model (P = 0.020). We have developed LIN-NPs that induce ROS generation as a novel anti-cancer agent for EOC. These findings have broad applications for cancer therapy.
This study aimed to evaluate the susceptibility in vitro and in vivo of Trypanosoma evansi to terpinen-4-ol, γ-terpinene and α-terpinene, the three main compounds of tea tree oil (Melaleuca alternifolia) with known efficacy in the treatment of trypanosomosis. In vitro, a trypanocidal effect of terpinen-4-ol, γ-terpinene, and α-terpinene was observed when used alone or associated at 0.5, 1 and 2% concentrations i.e., the α-terpinene showed a faster trypanocidal effect when compared to chemotherapy (diminazene aceturate - D.A.). In vivo studies were performed in two experiments: I and II where experiment I used T. evansi infected mice treated with terpinen-4-ol, γ-terpinene and α-terpinene alone (at a dose of 1.0 mL kg(-1).) or associated (two compounds, dose of 0.5 mL kg(-1) of each compound; tree compounds, dose of 0.335 mL kg(-1) of each compound); Treatment with α-terpinene was able to extend animal longevity, but showed no curative efficacy. In experiment II, T. evansi infected mice were treated with D.A. associate with α-terpinene, where a curative efficacy of 57.14% was found, a much better result when D.A. was used alone (14.28%). In summary, α-terpinene associated with D.A. can be used as an alternative treatment for T. evansi infection. The compound α-terpinene from M. alternifolia essential oil is the one responsible for the trypanocidal effect, a fact confirmed by in vitro results and the increased longevity observed on treated mice.
Purpose:
Calcitonin gene-related peptide (CGRP) is an effector of acute migraine attack. And the CGRP antagonisms have shown some early promise in the treatment of migraine. Here, we performed a meta-analysis to evaluate the efficacy of CGRP antagonisms in treating acute migraine attack.
Methods:
Pubmed, Cochrane Library, Web of Science and OvidSP were systematically searched up to 9 April 2015 for randomized controlled trials (RCTs) which is dealing with the efficacy of CGRP antagonisms in treating acute migraine attack. The bias and quality of RCTs were assessed with Cochrane collaboration's tool for assessing risk of bias. Reviewer manager 5.2 was utilized for data analysis.
Results:
Totally 13 publications matched the inclusion criteria, including 10 independent RCTs and 6803 patients. Pooled analysis indicated that CGRP antagonisms had better outcomes in number of patients with pain free at 2h, 2-24h sustained pain free, phonophobia free at 2h, patients with photophobia free at 2h and nausea free at 2h post-dose, as compared with placebo. But CGRP antagonisms were no superior than 5-HT agonists in the indices above mentioned.
Conclusions:
CGRP antagonisms may be an effective and promising treatment for acute migraine attack.
The requirements for an acceptable cannabis assay have changed dramatically over the years resulting in a large number of laboratories using a diverse array of analytical methodologies that have not been properly validated. Due to the lack of sufficiently validated methods, we conducted a single- laboratory validation study for the determination of cannabinoids and terpenes in a variety of commonly occurring cultivars. The procedure involves high- throughput homogenization to prepare sample extract, which is then profiled for cannabinoids and terpenes by HPLC-diode array detector and GC-flame ionization detector, respectively. Spike recovery studies for terpenes in the range of 0.03–1.5% were carried out with analytical standards, while recovery studies for Δ⁹ -tetrahydrocannabinolic acid, cannabidiolic acid, Δ⁹ -tetrahydrocannabivarinic acid, and cannabigerolic acid and their neutral counterparts in the range of 0.3–35% were carried out using cannabis extracts. In general, accuracy at all levels was within 5%, and RSDs were less than 3%. The interday and intraday repeatabilities of the procedure were evaluated with five different cultivars of varying chemotype, again resulting in acceptable RSDs. As an example of the application of this assay, it was used to illustrate the variability seen in cannabis coming from very advanced indoor cultivation operations.
A large number of monoterpenoids have been detected in or isolated from essential oils and solvent extracts of fungi, algae, liverworts, and higher plants, but the presence of monoterpenoids in fern is negligible. Vegetables, fruits, and spices contain monoterpenoids; however, their fate in human and other animal bodies has not yet been fully investigated systematically. The recent development of analytical instruments makes it easy to analyze the chemical structures of very minor components, and the essential oil chemistry field has dramatically developed.
The nano/macroporous polycaprolactone (PCL) microspheres with cell active surfaces were developed as an injectable cell delivery system. Room temperature ionic liquid (RTIL) and camphene were used as a liquid mold and a porogen, respectively. Various-sized spheres of 244-601μm with pores of various size and shape of 0.02-100μm, were formed depending on the camphene/RTIL ratio (0.8-2.6). To give cell activity, the surface of porous microspheres were further modified with nerve growth factors (NGF) containing gelatin to give a thin NGF/gelatin layer, to which the neural progenitor cells (PC-12) attached and extended their neurites on to the surface layers of the microspheres. The developed microspheres may be potentially applicable as a neuronal cell delivery scaffold for neuron tissue engineering.