Enhancing Tetrahydrocannabinol’s Therapeutic Efficacy in Inflammatory Bowel Disease: The Roles of Cannabidiol and the Cannabinoid 1 Receptor Allosteric Modulator ZCZ011

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 148 - 148

Published: Jan. 23, 2025

Background/Objectives: Current inflammatory bowel disease (IBD) treatments focus on symptomatic relief, highlighting the need for innovative approaches. Dysregulation of cannabinoid 1 (CB1) receptor, part endocannabinoid system, is linked to colitis. While tetrahydrocannabinol (THC) alleviates colitis via CB1 activation, its psychotropic effects limit clinical use. ZCZ011, a CB1R allosteric modulator, and cannabidiol (CBD), non-psychoactive cannabinoid, offer alternatives. This study investigated combining sub-therapeutic THC doses with ZCZ011 or CBD in murine model dextran sodium sulphate (DSS)-induced Methods: Acute was induced 4% DSS 7 days, followed by 3 days water. Chronic modelled over 24 alternating concentrations. The combination 2.5 mg/kg 20 10 evaluated. Key markers were assessed determine efficacy safety, including activity index (DAI), inflammation, cytokine levels, GLP-1, organ health. Results: DSS-induced resulted increased DAI scores, cytokines, inflammation dysregulation GLP-1 ammonia. at significantly improved but ineffective 5 mg/kg. alone showed transient effects. However, either alleviated markers, restored colon integrity reestablished homeostasis. also maintained favourable haematological biochemical profiles, notable reduction colitis-induced elevated ammonia levels. Conclusions: demonstrates synergistic potential low-dose combined as novel, effective safer therapeutic strategy ulcerative

Language: Английский

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The Silent Threat to Women’s Fertility: Uncovering the Devastating Effects of Oxidative Stress

Antioxidants, Journal Year: 2023, Volume and Issue: 12(8), P. 1490 - 1490

Published: July 26, 2023

Oxidative stress (OS), which arises through an imbalance between the formation of reactive oxygen species (ROS) and antioxidant defenses, plays a key role in pathophysiology female infertility, with latter constituting just one number diseases linked to OS as potential cause. The aim present article is review literature regarding association infertility. Among reproductive considered are endometriosis polycystic ovary syndrome (PCOS), while environmental pollutants, lifestyle variables, underlying medical conditions possibly resulting additionally examined. Current evidence points likely contributing above disorders, amount damage done by being influenced such variables duration severity exposure individual’s age genetic predisposition. Also discussed processes via may affect fertility, these including DNA mitochondrial dysfunction. Finally, last section manuscript contains evaluation treatment options, antioxidants modification, capable minimizing infertile women. prime message underlined this importance considering diagnosis Further studies are, nevertheless required identify best regimen its ideal duration.

Language: Английский

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Inflammation and cancer: friend or foe?

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

Published: May 10, 2024

Chronic inflammation plays a crucial role in the onset and progression of pathologies like neurodegenerative cardiovascular diseases, diabetes, cancer, since tumor development chronic are linked, sharing common signaling pathways. At least 20% breast colorectal cancers associated with triggered by infections, irritants, or autoimmune diseases. Obesity, inflammation, cancer interconnection underscore importance population-based interventions maintaining healthy body weight, to disrupt this axis. Given that dietary inflammatory index is correlated an increased risk adopting anti-inflammatory diet supplemented nutraceuticals may be useful for prevention. Natural products their derivatives offer promising antitumor activity favorable adverse effect profiles; however, natural bioactive drugs challenging due variability complexity, requiring rigorous research processes. It has been shown combining products, such as non-steroidal (NSAIDs), corticosteroids, statins, plant-derived demonstrate clinical utility accessible adjuvants traditional therapeutic approaches, known safety profiles. Pharmacological approaches targeting multiple proteins involved pathogenesis emerge particularly option. systemic multifactorial nature comprehensive strategies essential long term success therapy. To gain insights into carcinogenic phenomena discover diagnostic clinically relevant biomarkers, pivotal understand genetic variability, environmental exposure, habits, TME composition, establish based on molecular analysis. Furthermore, use endocannabinoid, cannabinoid, prostamide-type compounds potential targets biomarkers requires further investigation. This review aims elucidate specific etiological agents mediators contributing persistent reactions development. explores treatment, emphasizing urgent need cost-effective address cancer-associated inflammation.

Language: Английский

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Effects of a Cannabinoid-Based Phytocomplex (Pain ReliefTM) on Chronic Pain in Osteoarthritic Dogs

Animals, Journal Year: 2025, Volume and Issue: 15(1), P. 101 - 101

Published: Jan. 5, 2025

Twenty-one adult crossbreed dogs with chronic pain due to severe osteoarthrosis were enrolled in the study (placebo vs. treatment groups). The experimental group received dietary supplement (Pain ReliefTM, Giantec, Isernia, Italy) for 30 days evaluate its effects on metabolism and relief. During trial, Helsinki Chronic Pain Index significantly decreased (p < 0.01) group, indicating reduced improved quality of life. Additionally, treated showed improvements oxidative stress, demonstrated by a reduction reactive oxygen metabolites, an increase biological antioxidant potential. Interleukins 6 levels while interleukins 10 increased, thus suggesting anti-inflammatory effect supplement. Importantly, no adverse observed. Results suggest that ReliefTM is effective ameliorating osteoarthritis dogs, improving their

Language: Английский

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Evaluating the Mechanism of Cell Death in Melanoma Induced by the Cannabis Extract PHEC-66

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 268 - 268

Published: Jan. 31, 2024

Research suggests the potential of using cannabinoid-derived compounds to function as anticancer agents against melanoma cells. Our recent study highlighted remarkable in vitro effects PHEC-66, an extract from Cannabis sativa, on MM418-C1, MM329, and MM96L cell lines. However, complete molecular mechanism behind this action remains be elucidated. This aims unravel how PHEC-66 brings about its antiproliferative impact these lines, utilising diverse techniques such real-time polymerase chain reaction (qPCR), assays assess inhibition CB1 CB2 receptors, measurement reactive oxygen species (ROS), apoptosis assays, fluorescence-activated sorting (FACS) for cycle analysis. The outcomes obtained suggest that triggers lines by increasing expression pro-apoptotic markers (BAX mRNA) while concurrently reducing anti-apoptotic (Bcl-2 mRNA). Additionally, induces DNA fragmentation, halting progression at G1 checkpoint substantially elevating intracellular ROS levels. These findings imply might have adjuvant therapy treatment malignant melanoma. it is essential conduct further preclinical investigations delve deeper into efficacy.

Language: Английский

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First-year hemp farmers’ motives and resources to cultivate hemp

Journal of Agriculture Food Systems and Community Development, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: Jan. 1, 2025

Recent legislative changes have opened new ave­nues of hemp production for farmers seeking to diversify their operations. With the availability these opportunities comes need better understand decision making processes growers. The purpose this study was explore what motivated first-year grow and resources they utilized decision-making. Fifteen engaged in one-on-one interviews, which were ana­lyzed using qualitative research methods. Three dis­tinct themes emerged that undergirded farmer motivations hemp: personal characteristics, identified advantages as a crop, triala­bility compatibility. Additionally, four central sought out: grower networks, digital media, gov­ernment-based resources, print media. findings align with components Rogers’ Diffusion Innovation Theory recent related hemp-based prod­ucts. Based on findings, we recommend developing expanding educational those interested entering aid decision-making process assist them navigate entry into cultivation.

Language: Английский

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A Self-Emulsifying Nanococktail of Pomegranate and Cannabidiol Reduces Cognitive Decline in Mice

Nutrition and Dietary Supplements, Journal Year: 2025, Volume and Issue: Volume 17, P. 19 - 28

Published: Feb. 1, 2025

Introduction: Stress and inflammation in the early stages of cognitive decline has spurred interest use antioxidants as prophylactic therapeutic agents. Several studies have established neuroprotective capacities a pomegranate oil nano-formulation (Nano-PSO). In parallel, cannabis-derived cannabidiol (CBD) prevented social recognition deficits reduced neuroinflammation mice. This work assessed impact Nano-PSO:CBD on memory learning. Methods: A battery hemp extracts was screened for their effects acetylcholine esterase inhibition neuronal protection activities. The best-performing extract in-vitro assays nano-formulated via self-emulsifying system with PSO administered to aged mice MK-801-induced decline, which were then subjected Morris water maze test Y-maze test, respectively. Results: Aged chronically fed performed 22– 31% shorter escape latency (p ≤ 0.05), 23% distance swam increased average speed compared control Mice pretreated prior MK-801 had significantly higher percentage entries into novel arm untreated controls. Discussion: CBD salutary effect memory, learning spatial should be further studied clinical context. Keywords: cognition, nanoformulation, CBD, seed oil, nano-omega 5, brain protect, punicic acid

Language: Английский

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Δ9-Tetrahydrocannabinol induces blood-brain barrier disruption: involving the activation of CB1R and oxidative stress

Neuropharmacology, Journal Year: 2025, Volume and Issue: 270, P. 110366 - 110366

Published: Feb. 15, 2025

Language: Английский

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Phytomolecules as Alzheimer’s Therapeutics: A Comprehensive Review

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 288, P. 117401 - 117401

Published: Feb. 18, 2025

Language: Английский

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Involvement of SIRT3/FOXO1 and TLR4/NF-κB/NLRP3 pathways in protective effects of Δ(9)-tetrahydrocannabinol on diabetic cardiomyopathy in rats

Turkish Journal of Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Abstract Objectives Diabetic cardiomyopathy (DCM) is a chronic complication of type 2-diabetes mellitus, leading to heart failure. Addressing DCM requires comprehensive therapeutic approach. This study examines the protective role Δ(9)-tetrahydrocannabinol (THC) in by assessing its impact on cardiac function, inflammation, oxidative stress, and mitochondrial health exploring involvement SIRT3/FOXO1 TLR4/NF-κB/NLRP3 signaling pathways. Methods Over four-week period, THC (1.5 mg/kg, administered intraperitoneally) was given type-2 diabetic Sprague-Dawley rats. Cardiac function evaluated using carotid catheter vivo while integrity assessed through fluorometric techniques. Moreover, biochemical biomarkers protein expression key proteins were measured via ELISA immunoblotting. Results Compared untreated rats, treatment showed pronounced effects, improving reducing markers DCM. It significantly lowered NF-κB, NLRP3, IL-1β, TNF-α diabetes-induced stress heart, as evidenced decreased malondialdehyde levels increased glutathione catalase levels. also prevented membrane depolarization reactive oxygen species production substantially suppressed upregulation TLR4 MyD88 increasing FOXO1 Inhibition pathway 3-TYP reversed cardioprotective effects THC, negating NF-κB/NLRP3/IL-1β without influencing TLR4/MyD88. Conclusions These results underscore that offers significant protection against damage mitigating functional changes associated with DCM, primarily modulation SIRT3/FOXO1/mitochondrial

Language: Английский

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