The Ritchie Centre, Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Level 5, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria, 3168, Australia.
Monash Proteomics and Metabolomics Facility, Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Reprod Sci. 2021 May;28(5):1489-1497. doi: 10.1007/s43032-020-00439-5. Epub 2021 Jan 6.
Sulforaphane, an isothiocyanate found in cruciferous vegetables such as broccoli, shows promise as an adjuvant therapy for preeclampsia. To inform future clinical trials, we set out to determine the bioavailability of sulforaphane in non-pregnant and preeclamptic women. In six healthy female volunteers, we performed a crossover trial to compare the bioavailability of sulforaphane and metabolites afforded by an activated and non-activated broccoli extract preparation. We then undertook a dose escalation study of the activated broccoli extract in 12 women with pregnancy hypertension. In non-pregnant women, an equivalent dose of activated broccoli extract gave higher levels of sulforaphane and metabolites than a non-activated extract (p < 0.0001) and greater area under the curve (AUC) (3559 nM vs. 2172 nM, p = 0.03). Compared to non-pregnant women, in women with preeclampsia, the same dose of activated extract gave lower levels of total metabolites (p < 0.000) and AUC (3559 nM vs. 1653 nM, p = 0.007). Doubling the dose of the activated extract in women with preeclampsia doubled levels of sulforaphane and metabolites (p = 0.02) and AUC (1653 nM vs. 3333 nM, p = 0.02). In women with preeclampsia, activated broccoli extract was associated with modest decreases in diastolic blood pressure (p = 0.05) and circulating levels of sFlt-1 (p = 0.0002). A myrosinase-activated sulforaphane formulation affords better sulforaphane bioavailability than a non-activated formulation. Higher doses of sulforaphane are required to achieve likely effective doses in pregnant women than in non-pregnant women. Sulforaphane may improve endothelial function and blood pressure in women with pregnancy hypertension.
西兰花等十字花科蔬菜中含有的萝卜硫素作为子痫前期的辅助治疗方法具有广阔的应用前景。为了指导未来的临床试验,我们旨在确定萝卜硫素在非妊娠和子痫前期妇女中的生物利用度。在 6 名健康的女性志愿者中,我们进行了一项交叉试验,以比较经过激活和未激活的西兰花提取物制剂提供的萝卜硫素和代谢产物的生物利用度。然后,我们在 12 名患有妊娠高血压的女性中进行了萝卜硫素激活西兰花提取物的剂量递增研究。在非妊娠女性中,与非激活提取物相比,激活的西兰花提取物的等效剂量可产生更高水平的萝卜硫素和代谢产物(p<0.0001)和更大的曲线下面积(AUC)(3559 nM 比 2172 nM,p=0.03)。与非妊娠女性相比,患有子痫前期的女性给予相同剂量的激活提取物时,总代谢产物的水平和 AUC 均较低(3559 nM 比 1653 nM,p<0.000)。在患有子痫前期的女性中,将激活提取物的剂量增加一倍,可使萝卜硫素和代谢产物的水平增加一倍(p=0.02),AUC 也增加一倍(1653 nM 比 3333 nM,p=0.02)。在患有子痫前期的女性中,激活的西兰花提取物可使舒张压适度降低(p=0.05)和循环中 sFlt-1 水平降低(p=0.0002)。与非激活制剂相比,经过糜蛋白酶激活的萝卜硫素制剂可提供更好的萝卜硫素生物利用度。与非妊娠女性相比,妊娠女性需要更高剂量的萝卜硫素才能达到可能的有效剂量。萝卜硫素可能改善妊娠高血压女性的内皮功能和血压。