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  • Endocannabinoid System (ECS), Inflammation
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Non-psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors-, endocannabinoids-, and NF-κB-mediated signaling

Abstract Cannabis sativa L. is increasingly emerging for its protective role in modulating neuroinflammation, a complex process orchestrated among others by microglia, the resident immune cells of the central nervous system. Phytocannabinoids, especially cannabidiol (CBD), terpenes, and other constituents trigger several upstream and downstream microglial intracellular pathways. Here, we investigated the molecular mechanisms of a CBD- and terpenes-enriched C. sativa extract (CSE) in an in vitro model of neuroinflammation. We evaluated the effect of CSE on the inflammatory response induced by exposure to lipopolysaccharide (LPS) in BV-2 microglial cells, compared with CBD and β-caryophyllene (CAR), CB2 receptors (CB2r) inverse and full agonist, respectively. The LPS-induced upregulation of the...
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Anti-inflammatory effects of cannabidiol against lipopolysaccharides in cardiac sodium channels

Abstract Background Sepsis, caused by a dysregulated response to infections, can lead to cardiac arrhythmias. However, the mechanisms underlying sepsis-induced inflammation, and how inflammation provokes cardiac arrhythmias, are not well understood. We hypothesized that cannabidiol (CBD) may ameliorate lipopolysaccharide (LPS)-induced cardiotoxicity, via Toll-like receptors (TLR4) and cardiac sodium channels (NaV1.5). Methods and results We incubated human immune cells (THP-1 macrophages) with LPS for 24 h, then extracted the THP-1 incubation media. ELISA assays showed that LPS (1 or 5 μg·ml−1), in a concentration-dependent manner, or MPLA (TLR4 agonist, 5 μg·ml−1) stimulated the THP-1 cells to release inflammatory cytokines (TNF-α and IL-6). Prior incubation (4 h) with CBD (5 μM)...
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Cannabidiol Improves Random-Pattern Skin Flap Survival in Rats: Involvement of Cannabinoid Type-2 Receptors

Please use this link to access publication Abstract Background One of the major complications associated with random-pattern skin flaps is distal necrosis. Cannabidiol (CBD) has recently gained much attention as a therapeutic anti-inflammatory agent. We aimed to evaluate the efficacy of CBD on the random-pattern skin flap survival (SFS) in rats and to explore the possible involvement of cannabinoid type-2 (CB2) receptors. Methods In this controlled experimental study, we randomly divided male Wistar rats into seven study groups (six rats each). We performed a random-pattern skin flap model in each rat following pretreatment with vehicle (control) or multiple doses of CBD (0.3, 1, 5, or 10 mg/kg)....
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Cannabidiol Improves Antioxidant Capacity and Reduces Inflammation in the Lungs of Rats with Monocrotaline-Induced Pulmonary Hypertension

Abstract: Cannabidiol (CBD) is a plant-derived compound with antioxidant and anti-inflammatory properties. Pulmonary hypertension (PH) is still an incurable disease. CBD has been suggested to ameliorate monocrotaline (MCT)-induced PH, including reduction in right ventricular systolic pressure (RVSP), a vasorelaxant effect on pulmonary arteries and a decrease in the white blood cell count. The aim of our study was to investigate the effect of chronic administration of CBD (10 mg/kg daily for 21 days) on the parameters of oxidative stress and inflammation in the lungs of rats with MCT-induced PH. In MCT-induced PH, we found a decrease in total antioxidant capacity (TAC) and glutathione level...
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Cannabidiol Does Not Impact Acute Anabolic or Inflammatory Signaling in Skeletal Muscle In Vitro

Abstract Background: Cannabidiol (CBD) is becoming increasingly popular for the treatment of clinical conditions including as an aid for muscle recovery. Previous work demonstrated that CBD exhibited mild effects on skeletal muscle, with a tendency to increase anabolic signaling and decrease inflammatory signaling. Methods: To gain mechanistic insight and extend these findings, we conducted a set of experiments using C2C12 myotubes. Results: Increasing the dose of CBD (1–5 μM) provided with insulin-like growth factor 1 (IGF-1) showed no effect on anabolic signaling through mTORC1 (S6K1 [Thr389], p=0.27; rpS6 [Ser240/244], p=0.81; or 4E-BP1 [Thr37/46], p=0.87). Similarly, inflammatory signaling through nuclear factor kappa B (NF-κB) (p105, p=0.88; p50, p=0.93; or phosphorylated p65 [Ser536], p=0.84) in response...
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Cannabidiol and Beta-Caryophyllene in Combination: A Therapeutic Functional Interaction

Abstract Cannabis contains over 500 distinct compounds, which include cannabinoids, terpenoids, and flavonoids. However, very few of these compounds have been studied for their beneficial effects. There is an emerging concept that the constituents of the cannabis plant may work in concert to achieve better therapeutic benefits. This study is aimed at determining if the combination of a minor cannabinoid (cannabidiol, CBD) and a terpene (beta-caryophyllene, BCP) works in concert and if this has any therapeutic value. We used an inflammatory pain model (formalin) in mice to test for any functionality of CBD and BCP in combination. First, we determined the analgesic effect of...
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Neuroprotection of Cannabidiol, Its Synthetic Derivatives and Combination Preparations against Microglia-Mediated Neuroinflammation in Neurological Disorders

Abstract The lack of effective treatment for neurological disorders has encouraged the search for novel therapeutic strategies. Remarkably, neuroinflammation provoked by the activated microglia is emerging as an important therapeutic target for neurological dysfunction in the central nervous system. In the pathological context, the hyperactivation of microglia leads to neuroinflammation through the release of neurotoxic molecules, such as reactive oxygen species, proteinases, proinflammatory cytokines and chemokines. Cannabidiol (CBD) is a major pharmacologically active phytocannabinoids derived from Cannabis sativa L. CBD has promising therapeutic effects based on mounting clinical and preclinical studies of neurological disorders, such as epilepsy, multiple sclerosis, ischemic brain injuries, neuropathic pain, schizophrenia and...
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The dose-dependent effect of a stabilized cannabidiol nanoemulsion on ocular surface inflammation and intraocular pressure

Please use this link to access this publication. Abstract Cannabidiol (CBD) is a phytocannabinoid that has a great clinical therapeutic potential. Few studies have been published on its efficacy in ocular inflammations while its impact on intraocular pressure (IOP), a major risk factor for glaucoma, remains unclear. Moreover, due to its lability and high lipophilicity, its formulation within a prolonged stable topical ophthalmic solution or emulsion able to penetrate the highly selective corneal barrier is challenging. Therefore, various CBD nanoemulsions (NEs) were designed and evaluated for stability in accelerated conditions. Further, the optimal formulation was tested on a murine LPS-induced keratitis inflammation model. Lastly, increasing CBD...
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Anti-inflammation and gingival wound healing activities of Cannabis sativa L. subsp. sativa (hemp) extract and cannabidiol: An in vitro study

Please use this link to access this publication. Abstract Objective To evaluate the anti-inflammatory and gingival wound healing activities of Cannabis sativa L. subsp. sativa (hemp) extract and cannabidiol (CBD). Design The cellular bioactivities of hemp extract and CBD were determined the inhibition of TNF-α and IL-1β in LPS-induced murine macrophage (RAW 264.7) cells by using ELISA while wound healing activity in human gingival fibroblast (HGF-1) cells was performed by a scratch test assay. The cytotoxicity was also concerned and evaluated by MTT assay. Results The hemp extract and CBD significantly decreased TNF-α release by up to 91.05 ± 2.91% and 50.78 ± 7.21% of LPS activity, respectively, in a dose-dependent manner, compared to 10 µg/mL hydrocortisone (61.67 ± 3.79%)....
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Prophylactic Administration of Cannabidiol Reduces Microglial Inflammatory Response to Kainate-Induced Seizures and Neurogenesis

Please use this link to access this publication. Abstract Microglia, the dynamic innate immune cells of the central nervous system, become activated in epilepsy. The process of microglial activation in epilepsy results in the creation of an inflammatory environment around the site of seizure onset, which contributes to the epileptogenic process and epilepsy progression. Cannabidiol (CBD) has been effective for use as an adjunctive treatment for two severe pediatric seizure disorders. Newly recognized as an Food and Drug Administration (FDA)-approved drug treatment in epilepsy, it has gained in popularity primarily for pain management. Although CBD is readily available in stores and online retailers, its...
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