Endocannabinoid System as a Promising Therapeutic Target in Inflammatory Bowel Disease – A Systematic Review

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 22, 2021

Inflammatory bowel disease (IBD) is a general term used to describe group of chronic inflammatory conditions the gastrointestinal tract unknown etiology, including two primary forms: Crohn's (CD) and ulcerative colitis (UC). The endocannabinoid system (ECS) plays an important role in modulating many physiological processes intestinal homeostasis, modulation motility, visceral sensation, or immunomodulation inflammation IBD. It consists cannabinoid receptors (CB1 CB2), transporters for cellular uptake ligands, endogenous bioactive lipids (Anandamide 2-arachidonoylglycerol), enzymes responsible their synthesis degradation (fatty acid amide hydrolase monoacylglycerol lipase), manipulation which through agonists antagonists system, shows potential therapeutic ECS disease. This review summarizes components on inflammation, suggesting advantages cannabinoid-based therapies

Language: Английский

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Cannabinoid receptor-2 attenuates neuroinflammation by promoting autophagy-mediated degradation of the NLRP3 inflammasome post spinal cord injury

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 26, 2022

Neuroinflammation following spinal cord injury (SCI) results in prolonged neurological damage and locomotor dysfunction. Polarization of microglia is vital to regulation neuroinflammation, although the underlying mechanisms have not yet been elucidated. Endocannabinoid receptor subtype 2 (CB2R) reported ameliorate neurodegeneration via immunomodulation activities. However, machinery context SCI remains unclear.A lipopolysaccharide-induced inflammation model a mouse were employed investigate regulatory role CB2R polarization response excess neuroinflammation. Markers autophagy measured by Western blot analysis, immunofluorescence, flow cytometry, enzyme-linked immunosorbent assays. Histological staining with hematoxylin eosin, Nissl, Luxol® fast blue was conducted using commercial kits. The function hindlimbs experimental mice evaluated Basso Mouse Scale, Louisville Swim footprint assay.The showed that promoted M2 differentiation, increased interleukin (IL)-10 expression, inhibited M1 differentiation decreased expression IL-1β IL-6. activation also ubiquitination NLRP3 inflammasome interacted autophagy-related proteins p62 microtubule-associated 1B light chain 3. Treatment activator JWH-133 reduced loss myelin, apoptosis neurons, glial scarring, leading improved functional recovery hindlimbs, while antagonist AM630 produced opposite results.Taken together, these suggested attenuated neuroinflammation targeting microglial promoting clearance, thereby facilitating post-SCI.

Language: Английский

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Perineural Invasion in Pancreatic Ductal Adenocarcinoma: From Molecules towards Drugs of Clinical Relevance

Cancers, Journal Year: 2022, Volume and Issue: 14(23), P. 5793 - 5793

Published: Nov. 24, 2022

Pancreatic ductal adenocarcinoma is one of the most threatening solid malignancies. Molecular and cellular mediators that activate paracrine signalling also regulate dynamic interaction between pancreatic cancer cells nerves. This reciprocal interface leads to perineural invasion (PNI), defined as ability invade nerves, similar vascular lymphatic metastatic cascade. Targeting PNI in might help ameliorate prognosis pain relief. In this review, modern knowledge has been analysed critically presented. We focused on molecular pathways promoting progression, with particular emphasis neuropathic generation, we reviewed current pharmacological inhibitors axis. represents a common hallmark PDAC correlates recurrence, poor patients. The among cells, immune nerves biologically relevant each stage disease stimulates great interest, but real impact administration novel agents clinical practice limited. It still early days for PNI-targeted treatments, further advanced studies are needed understand whether they could be effective tools setting.

Language: Английский

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Cannabinol: History, Syntheses, and Biological Profile of the Greatest “Minor” Cannabinoid

Plants, Journal Year: 2022, Volume and Issue: 11(21), P. 2896 - 2896

Published: Oct. 28, 2022

Cannabis (Cannabis sativa L.) is an outstanding source of bioactive natural products, with more than 150 different phytocannabinoids isolated throughout the decades; however, studies their bioactivity have historically concentrated on so-called "big four" [∆9-THC (1a), CBD (2a), CBG (3a) and CBC (4a)]. Among remaining which traditionally been referred to as "minor cannabinoids", cannabinol (CBN, 5a) stands out for its important repercussions implications global scientific landscape. Throughout this review, we will describe why CBN (5a) deserves a prominent place within "cannabinome", providing overview history, syntheses developed, bioactivity, highlighting promising pharmacological potential significant impact that study chemistry had development new synthetic methodologies.

Language: Английский

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Endocannabinoid Modulation in Neurodegenerative Diseases: In Pursuit of Certainty

Biology, Journal Year: 2022, Volume and Issue: 11(3), P. 440 - 440

Published: March 14, 2022

Neurodegenerative diseases are an increasing cause of global morbidity and mortality. They occur in the central nervous system (CNS) lead to functional mental impairment due loss neurons. Recent evidence highlights link between neurodegenerative inflammatory CNS. These typically associated with several neurological disorders. have fundamental differences regarding their underlying physiology clinical manifestations, although there aspects that overlap. The endocannabinoid (ECS) is comprised receptors (type-1 (CB1R) type-2 (CB2R) cannabinoid-receptors, as well transient receptor potential vanilloid 1 (TRPV1)), endogenous ligands enzymes synthesize degrade endocannabinoids (ECBs). studies revealed involvement ECS different pathological these present review will explore roles cannabinoid (CBRs) pharmacological agents modulate CBRs or activity reference Alzheimer’s Disease (AD), Parkinson’s (PD), Huntington’s (HD) multiple sclerosis (MS).

Language: Английский

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Cannabinoids and triple-negative breast cancer treatment

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 8, 2024

Triple-negative breast cancer (TNBC) accounts for about 10-20% of all cases and is associated with an unfavorable prognosis. Until recently, treatment options TNBC were limited to chemotherapy. A new successful systemic immunotherapy immune checkpoint inhibitors, but tumor-specific biomarkers are needed improve patient outcomes. Cannabinoids show antitumor activity in most preclinical studies models do not appear have adverse effects on Clinical data evaluate efficacy safety humans. Importantly, the endocannabinoid system linked immunosuppression. Therefore, cannabinoid receptors could be a potential biomarker inhibitor therapy or novel mechanism reverse resistance immunotherapy. In this article, we provide overview currently available information how cannabinoids may influence standard TNBC.

Language: Английский

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Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System

Biomolecules, Journal Year: 2021, Volume and Issue: 11(6), P. 790 - 790

Published: May 24, 2021

Neurodegenerative disorders are a widespread cause of morbidity and mortality worldwide, characterized by neuroinflammation, oxidative stress neuronal depletion. The broad-spectrum neuroprotective activity the Mediterranean diet is widely documented, but it not yet known whether its nutritional caloric balance can induce modulation endocannabinoid system. In recent decades, many studies have shown how tone enhancement may be promising new therapeutic strategy to counteract main hallmarks neurodegeneration. From phylogenetic point view, human co-evolution between system dietary habits could play key role in pro-homeostatic lifestyle: this adaptive among our ancestors has been compromised modern Western diet, resulting “clinical deficiency syndrome”. This review aims evaluate evidence accumulated literature on neuroprotective, immunomodulatory antioxidant properties related system, suggesting prospects for research clinical interventions against neurodegenerative diseases light nutraceutical paradigm.

Language: Английский

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Cannabidiol treatment improves metabolic profile and decreases hypothalamic inflammation caused by maternal obesity

Frontiers in Nutrition, Journal Year: 2023, Volume and Issue: 10

Published: March 9, 2023

The implications of maternal overnutrition on offspring metabolic and neuroimmune development are well-known. Increasing evidence now suggests that obesity poor dietary habits during pregnancy lactation can increase the risk central peripheral dysregulation in offspring, but mechanisms not sufficiently established. Furthermore, despite many studies addressing preventive measures targeted at mother, very few propose practical approaches to treat damages when they already installed.Here we investigated potential cannabidiol (CBD) treatment attenuate effects induced by a cafeteria diet hypothalamic inflammation profile Wistar rats.We have observed range imbalances sex-dependant manner, with higher deposition visceral white adipose tissue, increased plasma fasting glucose lipopolysaccharides (LPS) levels both sexes, serum cholesterol triglycerides only occurred females, while insulin homeostatic model assessment index (HOMA-IR) was male offspring. We also found an overexpression pro-inflammatory cytokines tumor necrosis factor-alpha (TNFα), interleukin (IL) 6, 1β hypothalamus, trademark neuroinflammation. Interestingly, expression GFAP, marker for astrogliosis, reduced obese mothers, indicating adaptive mechanism utero Treatment 50 mg/kg CBD oil oral gavage able reduce tissue revert resistance males, LPS TNFα IL6 hypothalamus sexes.Together, these results indicate intricate interplay between counterparts pathogenicity therapeutic CBD. In this context, impairment internal circuitry caused neuroinflammation runs tandem disruptions important processes, which be attenuated ends.

Language: Английский

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The interplay of leptin and the peripheral endocannabinoid system in energy homeostasis and obesity; modulation by linoleic acid and exercise

Advanced Exercise and Health Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Receptor-Dependent and Independent Regulation of Voltage-Gated Ca2+ Channels and Ca2+-Permeable Channels by Endocannabinoids in the Brain

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(15), P. 8168 - 8168

Published: July 29, 2021

The activity of specific populations neurons in different brain areas makes decisions regarding proper synaptic transmission, the ability to make adaptations response external signals, as well triggering regulatory pathways sustain neural function. endocannabinoid system (ECS) appears be a very important, highly expressed, and active control central nervous (CNS). Functionally, it allows cells respond quickly processes that occur during but can also induce long-term changes. endocannabinoids (eCBs) belong large family bioactive lipid mediators includes amides, esters, ethers long-chain polyunsaturated fatty acids. They are produced "on demand" from precursors located membranes, exhibit short half-life, play key role retrograde messengers. eCBs act mainly through two receptors, CB1R CB2R, which G-protein coupled receptor superfamily (GPCRs), exert their action via multiple non-receptor pathways. depends on Ca2+, regulate downstream Ca2+ signaling. In this review, we focus regulation neuronal calcium channels by most effective members eCBs-2-arachidonoylglycerol (2-AG), anandamide (AEA) originating AEA-N-arachidonoylglycine (NAGly), better understand contribution ECS function under physiological conditions.

Language: Английский

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