María Eugenia Oliva

Introduction: Excessive intake of added sugars promotes metabolic disease, but the earliest myocardial responses to sugar-driven metabolic overload and their modulation by plant-derived bioactive compounds remain incompletely understood. We investigated whether a short-term sucrose-rich diet induces early cardiac remodeling and whether a full-spectrum cannabis oil (CO) can prevent these alterations. Methods: Male Wistar rats were assigned for 3 weeks to a reference diet, a sucrose-rich diet, or a sucrose-rich diet plus full-spectrum CO (cannabidiol [CBD]: tetrahydrocannabinol [THC] ratio 2:1; 1 mg/kg/day, orally). Results: Throughout the study period, the sucrose-rich diet significantly increased systolic and diastolic blood pressure (group effect, p = 0.0003 and p = 0.0029, respectively) and circulating cardiac injury markers (creatine kinase-MB [CK-MB], p = 0.0048; lactate dehydrogenase [LDH], p = 0.0173), promoted myocardial triglyceride accumulation ( p = 0.0002), and altered lipid metabolism-related regulators (e.g., fatty acid synthase [FAS], p = 0.0002; sterol regulatory element-binding protein 1c [SREBP-1c], p = 0.0007). These changes were accompanied by oxidative stress (reactive oxygen species [ROS], p < 0.0001), impaired antioxidant defenses (catalase [CAT], p < 0.0001), inflammatory and endothelial activation (nuclear factor-κB [NF-κB], p = 0.0049; vascular cell adhesion molecule-1 [VCAM-1], p < 0.0001), early fibrotic remodeling (myocardial collagen content, p < 0.0001), histological and ultrastructural injury, and increased cardiac cannabinoid receptor type 1 (CB ₁ R, p = 0.0001) and cannabinoid receptor type 2 (CB ₂ R, p = 0.0003) protein expression, whereas electrocardiographic parameters (heart rate, PR interval, QRS complex, corrected QT interval [QTc]) remained unchanged (all p > 0.05). Discussion: Cannabis oil administration prevented or markedly attenuated most of these alterations, including cardiac lipid accumulation, redox imbalance, inflammatory and remodeling-related signaling, structural damage, and cannabinoid receptor upregulation. These findings show that the myocardium is an early target of sucrose-driven metabolic overload and identify full-spectrum CO as a plant-derived bioactive intervention capable of limiting early cardiac metabolic and redox-inflammatory remodeling in this preclinical model. Further studies are required to define the contribution of individual phytocannabinoids and to determine whether cannabinoid receptor signaling contributes to these effects.

Introduction: Metabolic dysfunction–associated steatotic liver disease (MASLD) is closely linked to alterations in liver lipid metabolism, oxidative stress, fibrosis, and dysregulation of the endocannabinoid system (ECS). Although increasing evidence supports a role for cannabinoids in metabolic disorders, most preclinical studies have been conducted in male models, leaving female-specific responses largely unexplored. Methods: This study evaluated the effects of oral administration of a full-spectrum cannabis oil (CBD:THC 2:1) on MASLD-related alterations and ECS regulation in female Wistar rats fed a sucrose-rich diet (SRD). Rats were assigned to reference diet (RD), SRD, or SRD plus cannabis oil (1 mg/kg/day) for 3 weeks. Results: SRD-fed rats developed liver steatosis and increased NAFLD activity score (NAS), accompanied by enhanced de novo lipogenesis, reduced mitochondrial fatty acid oxidation, increased oxidative stress, early fibrotic changes, and ECS overactivation. Cannabis oil administration improved liver lipid metabolism, reduced NAS and fibrosis markers, attenuated lipid peroxidation and oxidative stress, increased NrF2 and decreased NF-κB p65 expression, and normalized hepatic CB1 expression and circulating endocannabinoid levels. Discussion: These findings demonstrate that full-spectrum cannabis oil is associated with improved MASLD-related outcomes and modulation of ECS tone in a female-specific model of diet-induced metabolic liver disease.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health concern globally, often associated with excessive sugar intake and metabolic dysregulation. In this study, we explored early hepatic alterations induced by a short-term sucrose-rich diet (SRD) and evaluated the preventive effects of a full-spectrum cannabis oil (CO) with a CBD:THC ratio of 2:1. Methods: Male Wistar rats were assigned to three groups: reference diet, SRD, and SRD plus CO (SRD + CO). CO was administered daily to the SRD + CO group from the onset of SRD exposure and throughout the 3-week experimental period. Liver fibrosis was assessed through hydroxyproline content, total collagen, TGF-β, and CB1R expression. Endothelial dysfunction was evaluated by measuring nitric oxide (NO) levels, endothelial nitric oxide synthase, myeloperoxidase, and VCAM-1 expression. Inflammatory responses were analyzed through hepatic expression of IL-10, TNF-α, PAI-1, MCP-1, F4/80, and CB2R. Transmission electron microscopy was performed on liver tissue to evaluate ultrastructural alterations. Results: SRD induced significant hepatic fibrosis, endothelial dysfunction, and inflammation. Ultrastructural analysis revealed nuclear alterations, including chromatin condensation, reduced mitochondrial number, intracellular lipid accumulation, increased glycogen deposits, and stromal changes characterized by perisinusoidal and periportal fibrosis with inflammatory cell infiltration. CO administration attenuated these pathological features and was accompanied by modulation of cannabinoid receptor expression. Conclusion: These findings highlight the preventive effects of CBD- and THC-containing CO against early liver alterations associated with MASLD.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder caused by oxidative stress and dysregulation of lipid metabolism. The endocannabinoid system (ECS), particularly the type 1 cannabinoid (CB1) receptor, plays a crucial role in NAFLD progression. Cannabinoids, such as cannabidiol (CBD) and tetrahydrocannabinol (THC), along with terpenes, such as beta-myrcene and d-limonene, have shown potential therapeutic effects on liver health, particularly in reducing oxidative stress and modulating lipid metabolism. This study aimed to analyse the effects of five cannabis oils (COs), each with different CBD:THC ratios and terpenes content, on hypertension, dyslipidemia, hepatic steatosis, oxidative stress, and CB1 receptor expression in an experimental model of NAFLD induced by a sucrose-rich diet (SRD) in Wistar rats for 3 weeks. Methods: Male Wistar rats were fed either a: (1) reference diet (RD; standard commercial laboratory diet) or a: (2) sucrose-rich diet (SRD) for 3 weeks. 3 to 7 SRD + CO as following: (3) SRD + THC; (4) SRD + CBD; (5) SRD + CBD:THC 1:1; (6) SRD + CBD:THC 2:1; and (7) SRD + CBD:THC 3:1. The COs were administered orally at a dose of 1.5 mg total cannabinoids/kg body weight daily. The cannabinoid and terpenes content of all COs used in the study was determined. The terpenes found in COs were beta-myrcene, d-limonene, terpinolene, linalool, beta-caryophyllene, alpha-humulene, (-)-guaiol, (-)-alpha-bisabolol. During the experimental period, body weight, food intake and blood pressure were measured. Serum glucose, triglyceride, total cholesterol, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP) levels were evaluated. Liver tissue histology, NAFLD activity score (NAS), triglyceride and cholesterol content, lipogenic enzyme activities, enzyme related to mitochondrial fatty acid oxidation, reactive oxygen species (ROS), thiobarbituric acid reactive substance (TBARS), and antioxidant enzyme activities were also evaluated. The CB1 receptor expression was also determined. Results: The results showed that SRD-fed rats developed hypertension, dyslipidemia, liver damage, hepatic steatosis, lipid peroxidation, and oxidative stress. This was accompanied by upregulation of liver CB1 receptor expression. CBD-rich CO, CBD:THC 1:1 ratio CO; CBD:THC 2:1 ratio CO and CBD:THC 3:1 ratio CO showed antihypertensive properties. THC-rich CO, CBD:THC 1:1 ratio CO; CBD:THC 2:1 ratio CO showed the greatest beneficial effects against hepatic steatosis and liver damage. All COs exhibited antioxidant effects in liver tissue. This was associated with normal liver CB1 receptor expression. Conclusions: This study demonstrated that COs, particularly THC-rich CO, CBD:THC ratio 1:1 CO, CBD:THC ratio 2:1 CO and terpenes, can effectively reduce dyslipidemia, liver damage and hepatic steatosis in SRD-induced NAFLD. COs with a higher proportion of CBD in their composition showed antihypertensive properties. All the COs exhibited antioxidant properties. These findings suggest that COs, especially those with CBD:THC ratios of 1:1 and 2:1 and terpenes, may represent a promising therapeutic approach for managing NAFLD and preventing its progression to more severe liver disease.

This study evaluated the effects and molecular mechanisms of astaxanthin (AXT) extracted from freshwater crabs (Dilocarcinus pagei) on lipotoxicity, impaired lipid metabolism, and oxidative stress in sucrose-rich diet (SRD) fed rats.

Introduction: This study aimed to analyze the effects of cannabis oil (cannabidiol:tetrahydrocannabinol [CBD:THC], 2:1 ratio) on the mechanisms involved in hepatic steatosis and oxidative stress in an experimental model of metabolic syndrome (MS) induced by a sucrose-rich diet (SRD). We hypothesized that noninvasive oral cannabis oil administration improves hepatic steatosis through a lower activity of lipogenic enzymes and an increase in carnitine palmitoyltransferase-1 (CPT-1) enzyme activity involved in the mitochondrial oxidation of fatty acids. Furthermore, cannabis oil ameliorates liver oxidative stress through the regulation of the main regulatory factors involved, nuclear factor erythroid 2 (NrF2) and nuclear factor-kB (NF-κB) p65. For testing this hypothesize, a relevant experimental model of MS was induced by feeding rats with a SRD for 3 weeks. Methods: Male Wistar rats were fed the following diets for 3 weeks: reference diet: standard commercial laboratory diet, SRD, and SRD + cannabis oil: noninvasive oral administration of 1 mg/kg body weight cannabis oil daily. The full-spectrum cannabis oil presents a total cannabinoid CBD:THC 2:1 ratio. Serum glucose, triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (AP), N-arachidonoylethanolamine or anandamide and 2-arachidonoylglycerol endocannabinoids levels, thiobarbituric acid reactive substance (TBARS) levels, and non-enzymatic antioxidant capacity (ferric ion-reducing antioxidant power [FRAP]) were evaluated. In the liver tissue: histology, nonalcoholic fatty liver disease activity score (NAS), triglycerides and cholesterol content, lipogenic enzyme activities (fatty acid synthase, acetyl-CoA carboxylase, malic enzyme, and glucose-6-phosphate dehydrogenase), enzyme related to mitochondrial fatty acid oxidation (CPT-1), reactive oxygen species, TBARS, FRAP, glutathione, catalase, glutathione peroxidase, and glutathione reductase enzyme activities. 4-hydroxynonenal, NrF2, and NF-κB p65 levels were analyzed by immunohistochemistry. Results: The results showed that SRD-fed rats developed dyslipidemia, liver damage, hepatic steatosis (increase of key enzymes related to the novo fatty acid synthesis and decrease of key enzyme related to mitochondrial fatty acid oxidation), lipid peroxidation, and oxidative stress. Hepatic NrF2 expression was significantly decreased and NF-κB p65 expression was increased. Cannabis oil administration improved dyslipidemia, liver damage, hepatic steatosis, lipid peroxidation (improving enzymes involved in lipid metabolism), and oxidative stress. In the liver tissue, NrF2 expression increased, and NF-κB p65 expression was reduced. Conclusion: The present study revealed new aspects of liver damage and steatosis, lipid peroxidation, and oxidative stress in dyslipidemic insulin-resistant SRD-fed rats. We demonstrated new properties and molecular mechanisms of cannabis oil (CBD:THC, 2:1 ratio) on lipotoxicity and hepatic oxidative stress in an experimental model of MS.

Metabolic syndrome (MS) is a cluster of risk factors for the development of cardiovascular disease and type 2 diabetes mellitus. Some dietary bioactive compounds such as peptides can exert dual antioxidant and anti-inflammatory effects. The aim of this study was to analyze the effects of microencapsulated brewers’ spent grain peptides (BSG-P-MC) on hepatic injury, lipid peroxidation, oxidative stress and inflammation in the liver-spleen axis in Wistar rats fed with a sucrose-rich diet (SRD). Male rats received for 100 days a reference diet (RD), SRD or RD and SRD containing 700 mg per kg body weight per day of BSG-P-MC. The results demonstrated that BSG-P-MC reversed injury, lipid peroxidation, and oxidative stress in the liver. For the spleen, BSG-P-MC decreased the levels of lipid peroxidation, CAT activity, NFκB, PAI-1 and F4/80 protein mass levels with respect to the SRD-fed rats. Three peptides identified by LC-MS/MS from BSG-P-MC after in vitro gastrointestinal digestion showed high in silico free radical scavenging activity (LPRDPYVDPMAPLPR, ANLPRDPYVDPMAPLPRSGPE and ANLPRDPYVDPMAPLPR). Moreover, two identified peptides presented high in silico anti-inflammatory properties (LTIGDTVPNLELDSTHGKIR and VDPDEKDAQGQLPSRT). This study is the first report of antioxidant and anti-inflammatory properties of microencapsulated BSG-peptides exerted in the liver-spleen axis in a MS rodent model.

The aim of study were to analyze liver inflammation and endothelial dysfunction in an experimental model of Metabolic Syndrome induced by administration of a sucrose-rich diet and to evaluate the effects of chia seed as a therapeutic strategy.