Effect of Long-Term Hydroxytyrosol Administration on Body Weight,Fat Mass and Urine Metabolomics: A Randomized Double-Blind Prospective Human Study

Hydroxytyrosol (HT) is a natural antioxidant found in olive products and characterized by well-documented beneficial effects on human health. Several research studies are ongoing that aim to investigate its potency and molecular mechanism of action. The present study aimed to investigate the potential effect of HT on human obesity through a randomized double-blind prospective design. HT in two different doses (15 and 5 mg/day) and a placebo capsule was administered to 29 women with overweight/obesity for six months and their weight and fat mass were monitored at three time points (baseline, 4, 12 and 24 weeks). Statistically significant weight and visceral fat mass loss (%weight loss: p = 0.012, %visceral fat loss: p = 0.006) were observed in the group receiving the maximum HT dosage versus placebo after 4 weeks of the intervention, with attenuation of these findings at 12 and 24 weeks of the study. Urine samples were collected during the intervention and analyzed via liquid chromatography–high-resolution mass spectrometry for untargeted metabolomic purposes and comparisons between study groups were performed. HT administration was safe and well-tolerated. To the best of our knowledge, this is the first human cohort investigating the effects of HT on obesity for a prolonged study period.     

应用UPLC-Orbitrap-MS分析草乌及其不同炮制品化学成分差异

草乌是有毒药之一,需经过炮制后方能使用。中药中草乌常用的炮制方法为水煮至内无白心,口尝微有麻舌感,蒙古族药中常用诃子制草乌,2种方法均能减毒。该实验利用UPLC-Orbitrap-MS对生草乌、药典法制草乌、诃子制草乌进行分析,比较炮制前后化学成分变化,为阐明诃子制草乌炮制减毒原理提供依据。通过比对生草乌与各炮制品的正负离子模式离子流出峰分析草乌炮制前后成分变化情况,并以化合物炮制前后离子峰面积比为炮制前后变化指数,将草乌主要活性成分经2种炮制方法炮制后的含量变化趋势进行对比,发现生草乌经药典法炮制后,新增14-O-anisoylneoline,dehydro-mesaconitine等14种成分,同时N-demethyl-mesaconitine,aconitine消失,且双酯型生物碱含量明显减少,单酯型和醇胺型生物碱含量明显增加,说明药典法制草乌是通过降低主要毒性成分双酯型生物碱的含量来减毒的;草乌经诃子汤炮制后,原草乌中含有的生物碱类化学成分变化较小,新增gallic acid,chebulic acid,shikimic acid等9种诃子中含有的化学成分,猜测诃子制草乌的减毒机制可能与诃子中化学成分有关。该研究结论表明药典法制草乌与诃子制草乌中化学成分有质的不同,二者具有不同的减毒原理。