Sui Ke, Tveter Kevin M, Bawagan Fiona G, Buckendahl Patricia, Martinez Savannah A, Jaffri Zehra H, MacDonell Avery T, Wu Yue, Duran Rocio M, Shapses Sue A, Roopchand Diana E
Department of Food Science, NJ Institute for Food Nutrition and Health (Rutgers Center for Lipid Research and Center for Nutrition Microbiome and Health), Rutgers, The State University of New Jersey, New Brunswick, NJ, United States.
Molecular Imaging Center, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States.
Front Pharmacol. 2022 Jun 21;13:900667. doi: 10.3389/fphar.2022.900667. eCollection 2022.
Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, inflammation, and increased risk of cardiometabolic disease and osteoporosis. The risk-benefit profile of hormone replacement therapy is not favorable in postmenopausal women therefore better treatment options are needed. Cannabidiol (CBD), a non-psychotropic phytocannabinoid extracted from hemp, has shown pharmacological activities suggesting it has therapeutic value for postmenopause, which can be modeled in ovariectomized (OVX) mice. We evaluated the efficacy of cannabidiol (25 mg/kg) administered perorally to OVX and sham surgery mice for 18 weeks. Compared to VEH-treated OVX mice, CBD-treated OVX mice had improved oral glucose tolerance, increased energy expenditure, improved whole body areal bone mineral density (aBMD) and bone mineral content as well as increased femoral bone volume fraction, trabecular thickness, and volumetric bone mineral density. Compared to VEH-treated OVX mice, CBD-treated OVX mice had increased relative abundance of fecal species and several gene expression changes in the intestine and femur consistent with reduced inflammation and less bone resorption. These data provide preclinical evidence supporting further investigation of CBD as a therapeutic for postmenopause-related disorders.
绝经后卵巢17β-雌二醇（E2）的丧失与肠道菌群失调、炎症以及心血管代谢疾病和骨质疏松症风险增加有关。激素替代疗法的风险效益状况对绝经后女性不利，因此需要更好的治疗选择。大麻二酚（CBD）是一种从大麻中提取的非精神活性植物大麻素，已显示出药理活性，表明其对绝经后具有治疗价值，这可以在去卵巢（OVX）小鼠中模拟。我们评估了对OVX和假手术小鼠口服给予大麻二酚（25mg/kg）18周的疗效。与给予赋形剂处理的OVX小鼠相比，给予CBD处理的OVX小鼠口服葡萄糖耐量得到改善，能量消耗增加，全身面积骨矿物质密度（aBMD）和骨矿物质含量提高，股骨骨体积分数、小梁厚度和体积骨矿物质密度增加。与给予赋形剂处理的OVX小鼠相比，给予CBD处理的OVX小鼠粪便物种的相对丰度增加，并且在肠道和股骨中有几种基因表达变化，这与炎症减轻和骨吸收减少一致。这些数据提供了临床前证据，支持进一步研究将CBD作为绝经后相关疾病的治疗方法。
