Effects of cannabidiol on miRNA expression in naïve mice
Ontology highlight
ABSTRACT: The non-psychotomimetic phytocannabinoid cannabidiol (CBD) has shown anticonvulsant effects in several seizure models in rats and mice. However, the mechanisms by which CBD exerts its antiepileptic effects are not fully elucidated. MicroRNAs (miRNA) are short non-coding RNAs which regulate protein expression. Dysregulation of miRNAs can contribute to the pathology of various diseases, including epilepsy. This could indicate that the modulation of miRNAs is a potential mechanism of action for the therapeutic effects of CBD. Therefore, we sequenced hippocampal samples from CBD or vehicle treated naive mice to see the effects of CBD on miRNA expression.
Project description:Cannabidiol (CBD) is a phytocannabinoid that has anti-inflammatory, immunomodulatory, antioxidant, anxiolytic, antipsychotic, and anticonvulsant effects. The metabolism of CBD occurs in the liver within a few hours after the dose is administered. This study aims to examine the effects of CBD on behavior, immune system activity, and stress levels, and to determine its impact on transcriptomic alterations in selected murine organs.
Project description:Cannabidiol (CBD) is a phytocannabinoid known for its anti-inflammatory, immunomodulatory, antioxidant, anxiolytic, antipsychotic, and anticonvulsant effects. The systemic administration of CBD also has the potential to impact kidney function, either beneficially or adversely. This study aims to examine the effects of CBD on behavior, immune system activity, and stress levels, and to determine its impact on transcriptomic alterations in selected organs of mice.
Project description:In the current study, we aimed at exploring the effects of the major non-psychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland functions. We found that CBD behaved as a highly effective anti-acne agent, targeting all the three key, sebocyte-specific steps of the pathogenesis (i.e. without compromising viability or basal sebaceous lipid production, CBD normalized pro-acne agents-induced excessive lipid synthesis, reduced proliferation and exerted anti-inflammatory actions). The goal of the present microarray analyses was to identify signaling pathways and target genes being involved in mediating the above beneficial effects of CBD.
Project description:In the current study, we aimed at exploring the effects of the major non-psychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland functions. We found that CBD behaved as a highly effective anti-acne agent, targeting all the three key, sebocyte-specific steps of the pathogenesis (i.e. without compromising viability or basal sebaceous lipid production, CBD normalized pro-acne agents-induced excessive lipid synthesis, reduced proliferation and exerted anti-inflammatory actions). The goal of the present microarray analyses was to identify signaling pathways and target genes being involved in mediating the above beneficial effects of CBD. Microarray analyses were performed by using three independent sets of control (vehicle-treated) and CBD-treated (10 M-NM-<M, 24-hr) human, immortalized SZ95 sebocytes. The first two sets of the samples were analyzed by two-color microarrays (M-bM-^@M-^\rep1M-bM-^@M-^] and M-bM-^@M-^\rep2M-bM-^@M-^]). Later on, the RNA from the second sample set was used for the M-bM-^@M-^\rep2-1M-bM-^@M-^] hybridization (techical repeat). Finally, we analyzed the third (biological) sample set by using one-color microarray (M-bM-^@M-^\rep3M-bM-^@M-^]).
Project description:Cannabidiol (CBD) oral spray on murine oral ulcer significantly inhibited inflammation, relieved pain and accelerated healing process. To gain insight into transcriptional regulation of CBD on cells related to healing progress of oral ulcer, we performed RNA-Seq on the immortalized human oral keratinocyte HOK-16B cell lines stimulated with LPS and ATP, after 10μM CBD or vehicle excipient pretreatment.
Project description:Cannabidiol (CBD), a phytochemical derived from Cannabis sativa L., has been demonstrated to exhibit promising anti-tumor properties in multiple cancer types. However, the effects of CBD on Hepatocellular carcinoma cells (HCC) remains unknown. We have shown that CBD effectively suppresses HCC cell growth in vivo and in vitro, and induced HCC cell pyroptosis in a caspase-3/GSDME-dependent manner. We further demonstrated that accumulation of Integrative Stress Response (ISR) and mitochondrial stress may contribute to the initiation of pyroptotic signaling by CBD. Simultaneously, CBD can repress aerobic glycolysis through modulation of the ATF4-IGFBP1-Akt axis, due to the depletion of ATP and crucial intermediate metabolites. Collectively, these observations indicate that CBD could be considered as a potential compound for HCC therapy.
Project description:Mutations in mitochondrial energy-producing genes lead to a heterogeneous group of untreatable disorders known as primary mitochondrial diseases (MD). Leigh syndrome (LS) is the most common pediatric MD and is characterized by progressive neuromuscular affectation and premature death. Here, we show that daily cannabidiol (CBD) administration significantly extends lifespan and ameliorates pathology in two LS mouse models, and cellular function in fibroblast from LS patients. CBD delays motor decline and neurodegenerative signs, improves social deficits and breathing abnormalities, decreases thermally induced seizures, and improves neuropathology in affected brain regions. Mechanistically, we identify peroxisome proliferator-activated receptor gamma (PPARg) as a key contributor to CBD’s beneficial effects, and provide proof of dysregulated PPARg expression and activity as a common feature in both mouse neurons and fibroblasts from LS patients. Taken together, our results provide the first evidence for CBD as a potential treatment for LS.
Project description:Cannabidiol (CBD) showed antiproliferative activity and induction of apoptosis in chronic myelogenous leukaemia cancer cells (K562 cells). A consolidated DARTS (Drug Affinity Response Target Stability) and t-LIP-MRM (targeted- Limited Proteolysis-Multiple Reaction Monitoring Mass spectrometry) platform was applied to unveil the interactome of CBD and to shed light on its mechanism of action. Both approaches point to the identification of DNA topoisomerase 2-alpha (TOP2A) as a major CBD target in K562 cells.
Project description:The spread of SARS-CoV-2 and ongoing COVID-19 pandemic underscores the need for new treatments. Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1a RNase endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against use of non-medical formulations including edibles, inhalants or topicals as a preventative or treatment therapy at the present time.
Project description:Cannabidiol (CBD) actions in the brain are largely complex and not fully understood. One important brain structure that is a target for CBD, and for which health-beneficial CBD consequences can be seen is the hypothalamus. Given the fundamental role of gene expression in the hypothalamus's regulatory functions, this study undertook the analysis of changes arising in hypothalamic cells’ transcriptomes following various CBD treatments. For this purpose, we used a hypothalamic cellular model, namely we employ adult-derived mHypoA-2/12 mouse cell lines. In the course of the study, the neural cells were treated with different CBD doses (ranging from 0.325 to 3 µM) and vehicle as a control for 6 and 24 hours. The experiment setup allowed us to evaluate both the dosage and time-dependent effect of CBD on hypothalamic cells, particularly on their viability, apoptosis, and transcriptome profile.