Effects of five cannabis oils with different CBD: THC ratios and terpenes on hypertension, dyslipidemia, hepatic steatosis, oxidative stress, and CB1 receptor in an experimental model.

IF 4.3 Q1 PHARMACOLOGY & PHARMACY
Valentina Degrave, Michelle Berenice Vega Joubert, Camila Filippa, Paola Ingaramo, Lucía Torregiani, Yamile Soledad Caro, María Mercedes De Zan, María Eugenia D'Alessandro, María Eugenia Oliva
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引用次数: 0

Abstract

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.

不同CBD: THC比例和萜烯的五种大麻油对高血压、血脂异常、肝脂肪变性、氧化应激和CB1受体的影响
背景:非酒精性脂肪性肝病(NAFLD)是一种由氧化应激和脂质代谢失调引起的常见肝脏疾病。内源性大麻素系统(ECS),特别是1型大麻素(CB1)受体,在NAFLD的进展中起着至关重要的作用。大麻素,如大麻二酚(CBD)和四氢大麻酚(THC),以及萜烯,如β -月桂烯和d-柠檬烯,已显示出对肝脏健康的潜在治疗作用,特别是在减少氧化应激和调节脂质代谢方面。本研究旨在分析不同CBD:THC比例和萜烯含量的五种大麻油(COs)对Wistar大鼠富蔗糖饮食(SRD)诱导的NAFLD实验模型中高血压、血脂异常、肝脂肪变性、氧化应激和CB1受体表达的影响。方法:雄性Wistar大鼠分别饲喂:(1)参考日粮(RD;标准商业实验室饮食)或(2)富蔗糖饮食(SRD) 3周。3 ~ 7 SRD + CO如下:(3)SRD + THC;4) srd + cbd;(5) srd + cbd: thc 1:1;(6) srd + cbd: thc 2:1;(7) SRD + CBD:THC 3:1。COs每天口服总大麻素1.5 mg /kg体重。测定了研究中使用的所有COs的大麻素和萜烯含量。在COs中发现的萜烯有-月桂烯、d-柠檬烯、松油烯、芳樟醇、-石竹烯、-葎草烯、(-)-愈创木酚、(-)- - -双abolol。实验期间测定大鼠体重、摄食量和血压。测定血清葡萄糖、甘油三酯、总胆固醇、尿酸、谷丙转氨酶(ALT)、天冬氨酸转氨酶(AST)和碱性磷酸酶(AP)水平。评估肝脏组织组织学、NAFLD活性评分(NAS)、甘油三酯和胆固醇含量、脂肪生成酶活性、线粒体脂肪酸氧化相关酶、活性氧(ROS)、硫代巴比妥酸活性物质(TBARS)和抗氧化酶活性。测定CB1受体的表达。结果:srd喂养大鼠出现高血压、血脂异常、肝损害、肝脂肪变性、脂质过氧化和氧化应激。这伴随着肝脏CB1受体表达的上调。富含CBD的CO, CBD:THC 1:1比CO;CBD:THC 2:1比CO和CBD:THC 3:1比CO具有降压作用。富THC CO, CBD:THC 1:1比CO;CBD:THC 2:1比CO对肝脂肪变性和肝损害的有益作用最大。所有COs在肝组织中均表现出抗氧化作用。这与正常的肝脏CB1受体表达有关。结论:本研究表明,COs特别是富含THC的CO、CBD:THC比1:1 CO、CBD:THC比2:1 CO和萜烯类化合物可有效降低srd诱导的NAFLD的血脂异常、肝损害和肝脂肪变性。CBD含量较高的COs具有抗高血压的作用。所有COs均表现出抗氧化性能。这些发现表明,COs,特别是那些CBD:THC比例为1:1和2:1和萜烯的COs,可能是一种有希望的治疗NAFLD和防止其发展为更严重肝脏疾病的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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