Cannabidiol (CBD) Upregulates Vitamin D3 Receptors (VDRs) Expression That Modulates Cytokines (TNF-α, IL-6), Tissue Elasticity, Cellular Senescence, and Mitochondrial ATP Generation in Human and Rodent Cell Lines

IF 1.3 Q4 NUTRITION & DIETETICS

Nutrition and Dietary Supplements Pub Date : 2023-11-01 DOI:10.2147/nds.s435447

Mahendra Trivedi, Alice Branton, Dahryn Trivedi, Sambhu Mondal, Snehasis Jana

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引用次数: 0

Abstract

Background: Cannabidiol (CBD) is a non-psychoactive cannabinoid derived from Cannabis sativa L. with very low toxicity for human and a wide variety of therapeutic uses as medicine. The study objective is to evaluate the impact of CBD on vitamin D 3 receptor (VDR) protein expressions, tissue elasticity, anti-inflammatory, and anti-senescence activity in human and rodent cell lines. Methods: Cell viability was estimated by MTT assay. Relative quantification (RQ) of VDR protein expression was measured by RT-PCR. Tissue elasticity was measured by atomic force microscopy (AFM). Cellular senescence and ATP were performed using trypan blue exclusion test and colorimetric assay, respectively. Results: Cell viability assay data showed CBD was safe and nontoxic upto 7.5 μM. The VDR protein expression was significantly increased by 109.71% ( p = 0.013), 236.96% ( p ≤ 0.001), 170% ( p ≤ 0.001), 100% ( p = 0.019), 80% ( p = 0.021), 427.27% ( p ≤ 0.001), 366.67% ( p ≤ 0.001), 56.31% ( p = 0.016), and 63.84% ( p ≤ 0.001) in MG-63, MDA-MB-231, SH-SY5Y, HEK-293, HT-29, EaHy-926, HepG2, A-549, and C2C12 cells, respectively compared to the normal control group. CBD treatment significantly reduced the levels of TNF-α (46.58%; p ≤ 0.049) and IL-6 (43.61%; p ≤ 0.001) at CBD-5 μM compared to the vehicle control group. Tissue elasticity was significantly ( p ≤ 0.001) increased by 37.09% and 49.49% in CBD-2.5 and CBD-5 μM, respectively, compared to the vehicle control group. Significantly ( p ≤ 0.001) reduced senescence cells by 39.22% in CBD-5 μM than the vehicle control group. The level of ATP was significantly ( p ≤ 0.001) increased by 90.55, 117.06, and 153.54% in CBD-1, CBD-2.5, and CBD-5 μM, respectively, compared to the vehicle control group. Conclusion: Overall, data suggest that CBD considerably improved VDR protein expression, inflammation, cell growth, tissue elasticity, and enhanced mitochondrial bioenergetics in multiple cell lines. In this study, for the first time, we showed the evidence suggesting that the VDR plays a critical and multifaceted role in various types of human cells. Keywords: cannabidiol, inflammation, elasticity, VDR expression, senescence, ATP

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大麻二酚(CBD)上调维生素D3受体(VDRs)的表达，调节人类和啮齿动物细胞系中细胞因子(TNF-α， IL-6)，组织弹性，细胞衰老和线粒体ATP的产生

背景:大麻二酚(Cannabidiol, CBD)是一种从大麻中提取的非精神活性大麻素，对人体毒性极低，作为药物有广泛的治疗用途。本研究的目的是评估CBD对人和啮齿动物细胞系维生素d3受体(VDR)蛋白表达、组织弹性、抗炎和抗衰老活性的影响。方法:采用MTT法测定细胞活力。RT-PCR检测VDR蛋白表达的相对定量(RQ)。用原子力显微镜(AFM)测定组织弹性。细胞衰老和ATP分别采用台盼蓝排除法和比色法测定。结果:细胞活力测定数据显示，CBD在7.5 μM范围内安全无毒。与正常对照组相比，MG-63、MDA-MB-231、SH-SY5Y、HEK-293、HT-29、EaHy-926、HepG2、A-549、C2C12细胞中VDR蛋白表达量分别显著升高109.71% (p = 0.013)、236.96% (p≤0.001)、170% (p≤0.001)、100% (p = 0.019)、80% (p = 0.021)、427.27% (p≤0.001)、366.67% (p≤0.001)、56.31% (p = 0.016)、63.84% (p≤0.001)。CBD治疗显著降低TNF-α水平(46.58%;p≤0.049)和IL-6 (43.61%;p≤0.001)。与对照组相比，CBD-2.5 μM组和CBD-5 μM组的组织弹性分别显著(p≤0.001)提高了37.09%和49.49%。与对照相比，CBD-5 μM组衰老细胞明显减少39.22% (p≤0.001)。与对照组相比，CBD-1、CBD-2.5和CBD-5 μM组ATP水平分别显著升高90.55%、117.06和153.54% (p≤0.001)。结论:总体而言，数据表明CBD可显著改善多种细胞系的VDR蛋白表达、炎症、细胞生长、组织弹性，并增强线粒体生物能量。在这项研究中，我们首次展示了证据，表明VDR在各种类型的人类细胞中起着关键的多方面作用。关键词:大麻二酚，炎症，弹性，VDR表达，衰老，ATP

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来源期刊

Nutrition and Dietary Supplements NUTRITION & DIETETICS-

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审稿时长

16 weeks

期刊介绍： Nutrition and Dietary Supplements is an international, peer-reviewed, open access journal focusing on research into nutritional requirements in health and disease, impact on metabolism and the identification and optimal use of dietary strategies and supplements necessary for normal growth and development. Specific topics covered in the journal include: Epidemiology, prevalence of related disorders such as obesity, diabetes, dyslipidemias Biochemistry and cellular metabolism of nutrients Effect of nutrition on metabolic control Impact of hormones and genetics on nutrient handling Identification of cofactors and development of effective supplementation strategies Dietary strategies Behavior modification Consumer and patient adherence, quality of life Public Health Policy & Health Economics.