405 research outputs found
Pharmacology of non-psychoactive phytocannabinoids and their potential for treatment of cardiometabolic disease.
No full textThe use of Cannabis sativa by humans dates back to the third millennium BC, and it has been utilized in many forms for multiple purposes, including production of fibre and rope, as food and medicine, and (perhaps most notably) for its psychoactive properties for recreational use. The discovery of Δ9-tetrahydrocannabinol (Δ9-THC) as the main psychoactive phytocannabinoid contained in cannabis by Gaoni and Mechoulam in 1964 (J Am Chem Soc 86, 1646–1647), was the first major step in cannabis research; since then the identification of the chemicals (phytocannabinoids) present in cannabis, the classification of the pharmacological targets of these compounds and the discovery that the body has its own endocannabinoid system (ECS) have highlighted the potential value of cannabis-derived compounds in the treatment of many diseases, such as neurological disorders and cancers. Although the use of Δ9-THC as a therapeutic agent is constrained by its psychoactive properties, there is growing evidence that non-psychoactive phytocannabinoids, derived from both Cannabis sativa and other plant species, as well as non-cannabinoid compounds found in Cannabis sativa, have real potential as therapeutics. This chapter will focus on the possibilities for using these compounds in the prevention and treatment of cardiovascular disease and related metabolic disturbances
What makes a cherry red?: an investigation into flavonoid pathway regulation in sweet cherry (Prunus avium L.) fruit.
No full textColour is an important fruit quality indicator because many consumers make their selections based primarily on this trait. Inheritance of colour has been studied within sweet cherry (Prunus avium L.) populations and as a result fruit colour is thought to be determined by three genetic factors. A flesh colour factor (F) and the major skin colour factor (A) are the main determinants of fruit colour, where red pigmentation is incompletely dominant over yellow. A third factor, the minor skin colour factor (B), can produce blush skin but is epistatically masked by a dominant A allele. The pigments that colour fruit are known as anthocyanins, synthesised via the transcriptionally regulated flavonoid pathway, which also synthesizes the related secondary metabolites, condensed tannins and flavonols. In other fruit and flower species, mutations in flavonoid pathway or regulatory genes can lead to non-functional alleles that explain the inheritance of colour. However the genes encoding the genetic colour factors are not known in sweet cherry. Therefore, this research has endeavoured to study the cherry flavonoid pathway and its transcriptional regulation, with a view to determining the genetic differences responsible for yellow, blush, red and black cultivars. To achieve this aim, genes encoding flavonoid pathway enzymes and putative regulators of flavonoid synthesis were isolated from the red sweet cherry cultivar ‘Lapins’. PaMYBA1, an R2R3-MYB factor, possessing a high degree of sequence similarity with characterised anthocyanin regulators and conserved C-terminal motifs common within this type of protein, was identified. Functional characterisation of PaMYBA1 demonstrated its ability to activate transcription from the promoters of chalcone synthase (MdCHS), which encodes an enzyme that performs the first committed step in the synthesis of flavonoids, and the anthocyanin biosynthetic gene UDP-glycosyl:flavonoid-3-O-glycosyltransferase (MdUFGT). Furthermore, correlation between anthocyanin accumulation and the expression profile of PaMYBA1 in developing ‘Lapins’ fruit and light-treated blush-skinned ‘Ranier’ fruit suggest that PaMYBA1 might be an important colour factor. Transcript analysis revealed that PaMYBA1 is necessary for the production of colour in cherries; PaMYBA1 is not expressed in the solid yellow fruit of ‘Yellow Glass’ that lacks anthocyanins. However, similar levels of expression of PaMYBA1 in blush, red and black sweet cherry fruit indicate that there are additional factors that contribute to differences in colour intensity. The intense colour and increased flavonoid levels of the black sweet cherry ‘Sam’, compared with the blush and red fruits tested, correlated with a large increase in the expression of the putative tannin regulator PaMYBPA1 in this cultivar. In a functional assay, PaMYBPA1 could trans-activate not only the promoters of the tannin genes anthocyanidin reductase (VvANR) and leucaonthocyanidin reductase (VvLAR), but also of MdCHS and MdUFGT. Therefore, it is possible that PaMYBPA1 could regulate both tannin and anthocyanin synthesis, particularly when expressed at high levels. Taking into consideration the expression of flavonoid pathway genes in different sweet cherry cultivars and tissues, and under different environmental conditions, together with published scientific observations of the genetic factors contributing to fruit colour, we have developed a working model for flavonoid pathway regulation in sweet cherry fruit. Aspects of the model remain to be determined, such as the involvement of two additional anthocyanin-type MYB factors PaMYBA2 and PaMYBA3 in fruit pigmentation. However, it provides a general understanding of differences in the activity of the flavonoid pathway between sweet cherry cultivars, and moves us closer to knowing the identity of the inherited factors that determine skin and flesh colour in sweet cherry fruit.Thesis (Ph.D) -- University of Adelaide, School of Agriculture, Food and Wine, 201
New insights into the yin and yang of the endocannabinoid system in health and disease
No full textThis article is part of a themed section on Endocannabionoids, of which the author is guest editor. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc
Soil and water management in cherry orchards
No full textTitle from PDF caption (viewed on July 12, 2017).This archived document is maintained by the State Library of Oregon as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Mode of access: Internet from the Oregon Government Publications Collection.Text in English
Investigation into control of cherry fruit fly, Rhagoletis cerasi (L., 1758) (Diptera: Tephritidae), in organic cherry production
No full text1st International Organic Agriculture and Biodiversity Symposium -- SEP 27-29, 2017 -- Bayburt, TURKEYWOS: 000433021100004The study was conducted at two locations, Pozanti (Adana) and Darbogaz (Ulukisla, Nigde) in 2015-2017. It aimed to determine the effects of the emergence time of cherry fruit fly, Rhagoletis cerasi (L., 1758) (Diptera: Tephritidae), the dynamics of adult flight and the control methods that could be used in organic cherry production. It investigated the effectiveness of netting trees, textile mulch, mass capture, plant-based insecticides and insecticide application against cherry fruit fly. Population monitoring revealed that the population of cherry fruit fly was low at Pozanti and slightly higher at Darbogaz. Clear statistical differences were observed between the untreated control and the treatments evaluated. The most effective control was obtained from with netting (100% efficacy). It was concluded that the other methods evaluated could be useful in organic cherry production.Cukurova UniversityCukurova University [FDK-2015-3200]This study is the PhD project of senior author and was supported by Cukurova University as scientific research project number FDK-2015-3200
Natural products as sources of novel drugs.
No full textThis book reflects the state of the art in the field of natural product drug discovery. The work explores what advances have been made in discovering novel compounds from terrestrial, marine and microbial sources for use in the treatment and management of both non-communicable (e.g. cardiovascular, neurodegenerative) and communicable (e.g. malaria) diseases. Each chapter is authored by international experts who present detailed analysis of the pipeline of natural product-derived drugs in their field. This book makes a valuable contribution to the field and appeals to researchers in all branches of natural product research
Studies on the role of GPR55 in cardiovascular physiology and pathophysiology.
No full textAtherosclerosis is a multifactorial, chronic inflammatory condition characterised by endothelial dysfunction, hyperlipidaemia and the accumulation of fatty deposits within the tunica intima of medium-to-large sized muscular arteries. This disease can prove fatal with patients suffering lethal myocardial infarction or stroke. Recently, two studies investigating the role of G-protein-coupled receptor 55 (GPR55) in atherosclerosis reported conflicting results; one reported a pro-atherogenic role for GPR55 and the other, an anti-atherogenic role for this receptor. Interestingly, another study demonstrated that the activation of GPR55 by lysophosphatidylinositol (LPI) in cultured rat neonatal ventricular cardiomyocytes provokes distinct cellular functions that are dependent on the location of GPR55, leading to suggestions that GPR55 may regulate cardiomyocyte function at two cellular sites and be a potential therapeutic target for cardiac disorders. While it has been demonstrated that GPR55 is important in the maintenance of cardiac function of healthy mice, what is currently unknown is if GPR55 has a role in the cardiovascular remodelling and cardiac function of atherosclerosis prone mice. To address this, the present studies were conducted to investigate 1) the role of GPR55 in atherogenesis, 2) if GPR55 has a role in the cardiac function of mice suffering from atherosclerosis, 3) the signalling pathway by which LPI activates cardiomyocytes, 4) the impact of GPR55 activation on the outcome of myocardial ischaemia/reperfusion (I/R) injury and, 5) the signalling mechanisms by which GPR55 elicits any observed effects on the myocardium in response to such injury. Using C57BL/6 (wildtype; WT), apolipoprotein E knockout (ApoE-/-; mouse model of atherosclerosis), GPR55 knockout (GPR55-/-) and novel ApoE-/-/GPR55-/- mice, this study has established that in the presence of high fat feeding (to accelerate atherosclerosis), GPR55 has a complex role whereby it both regulates risk factors associated with atherosclerosis (i.e. body weight and fat mass) yet promotes the development of fatty streaks within the vasculature, via a lipid independent mechanism. In terms of cardiac function, GPR55 exerted a protective role by maintaining the systolic function of high fat fed ApoE-/- mice, yet negatively affected the contractile reserve of these mice. With regard to infarct size, the present study established that LPI-induced activation of GPR55 (pre-global ischaemia) exacerbates myocardial tissue injury via a Rho-associated protein kinase (ROCK) dependent mechanism. Finally, this study established that LPI signals through the same signalling pathway as it did in the isolated heart, in both mouse and human-induced pluripotent stem cell-derived cardiomyocytes thus suggesting a translational role for GPR55 in the human heart. In conclusion, despite further research being required, the data presented within this thesis provides evidence that GPR55 may have the potential to be targeted for therapeutic gains in atherosclerosis and myocardial I/R injury
Hydrocyanic Acid Potential of Black Cherry Leaves
No full textBlack cherry (Prunus serotina L.) leaves have been known to be a source of hydrocyanic acid poisoning of cattle since the late 1800 s. Results of early studies indicated that the black cherry was one of the most toxic of the cyanogenetic plants. An early idea which has persisted to the present has been that black cherry leaves must be wilted before they are toxic to cattle. Black cherry trees are found throughout the eastern United States and as far west as Arizona and North and South Dakota. In the spring of 1972, the author of the present study conducted a survey of County Agricultural Extension Agents in Kentucky to determine the distribution of black cherry trees in agricultural areas, and to evaluate the concern which cattle producers have about the threat of hydrocyanic acid poisoning from cherry trees. Survey questionnaires were returned by agents in 97 counties (Appendix A ). Some of the findings were: (1) black cherry trees are common occurrences in most counties; (2) several ruminant animals have died following the consumption of black cherry leaves, presumably from hydrocyanic acid poisoning; (3) approximately 83 percent of the respondents believed that black cherry leaves must be wilted before they are toxic; and (4) a majority of county agents indicated that their cattle producers either remove black cherry trees from pastures or check pasture areas after summer storms and remove any fallen cherry trees or branches. Objectives of the present study included: (1) to determine the levels of hydrocyanic acid potential (HCN-p) in black cherry leaves; (2) to determine whether there are HCN-p differences among black cherry trees; (3) to study the effect of aging of leaves on HCN-p; and (4) to ascertain the effect of wilting or drying of leaves on HCN-p
Determining the role of the LPI/GPR55 system in the development of obesity and associated cardiovascular consequences.
No full textObesity has reached worldwide epidemic proportions and with this increased incidence of obesity, comes an increase in incidence of the comorbidities associated with obesity such as diabetes and cardiovascular disease (CVD). The underlying mechanisms which connect these diseases are still poorly understood. One system which has been shown to be up-regulated in the setting of obesity and diabetes is that of the G-protein coupled receptor-55/Lysophosphatidylinositol (GPR55/LPI). Despite being upregulated in the setting of obesity, the function of GPR55 in obesity and other disease states remains elusive. Therefore, the present study aimed to 1) investigate the role of GPR55 in obesity by characterising the phenotype of the GPR55 knockout (GPR55-/-) mouse when challenged with a high fat diet (HFD) intervention, 2) elucidate any effect of the GPR55 knockout and HFD intervention on the myocardial infarct size sustained following a period of ischaemia/reperfusion (I/R) and 3) make use of an in vitro model to elucidate the mechanisms by which changes occur in the adipose tissue of mice fed a HFD. GPR55-/- mice fed a HFD for 12-weeks gained significantly more weight in the form of fat mass, compared to wild-type (WT) controls and consequently become obese. Obese GPR55-/- mice displayed hypertrophic adipose tissue concurrent with the significant dysregulation of plasma lipids, increases in specific circulating LPI species, increased lipid deposition within the liver and a change in adipose tissue gene expression profile. These changes were not observed in GPR55-/- mice fed a standard diet or WT mice fed a HFD. Following a period of I/R, the myocardial infarct size in hearts from WT HFD fed mice was significantly smaller than in hearts from WT standard diet fed mice. This reduction in infarct size due to HFD intervention was not dependent on RISK-pathway activation and was not observed in hearts from GPR55-/- mice, therefore demonstrating that the cardio-protective effect of a HFD on infarct size is dependent on GPR55. In vitro studies using 3T3-L1 cells determined that the changes in adipose tissue gene expression of HFD fed mice was not due to enhanced stimulation with LPI or via hypoxic mechanisms. The results of these studies demonstrate that GPR55 has an anti-obesity function in vivo and also mediates the cardio-protective effect of a HFD on myocardial infarct size, through currently unknown mechanisms
Cellular mechanisms of acute hypoxic pulmonary vasoconstriction in intrapulmonary veins.
No full textIn the pulmonary circulation, alveolar hypoxia contributes to blood flow regulation. Hypoxic pulmonary vasoconstriction (HPV) involves both pulmonary arteries and veins, but little is known of the contractile mechanisms specific to the veins. The aim of these studies was to examine the hypoxic response in small porcine intrapulmonary veins in relation to the arterial response, and investigate the effects of hypoxia on ion conductances in single myocytes from intrapulmonary veins. In wire myography experiments, intrapulmonary veins contracted more than sizematched arteries in response to hypoxia and agonists KCl and PGF2α. Venous contractions were inhibited by removal of extracellular Ca2+ or in the presence of Clchannel blocker NFA, effects not seen in the arteries. To examine the mechanisms of venous contraction at cellular level, single pulmonary vein smooth muscle cells (PVSMC) were freshly isolated and characterised morphologically and electrophysiologically for the first time. In patch-clamp studies, hypoxia reversibly inhibited a whole-cell outward current in the presence of BKCa channel antagonist Penitrem A. By subtracting currents recorded in normoxia and hypoxia, a novel hypoxia-sensitive K+ current (IK(H)) was revealed in PVSMC. IK(H) was a rapidly activating, partially inactivating current and was sensitive to KV channel blocker 4-AP. The biophysical properties of IK(H) revealed the voltage window of current availability with a peak near the resting membrane potential of PVSMC. In conclusion, these findings highlight differences between the contractile properties of veins and arteries and reveal a significant contribution of Ca2+ influx and an NFA-sensitive conductance during venous contraction to agonists and hypoxia. Furthermore, the results suggest that a novel hypoxia-sensitive KV current contributes to membrane potential under resting conditions in PVSMC and its inhibition by hypoxia may contribute to the initiation of HPV in porcine intrapulmonary veins
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