Ilie Elena Iuliana, Popescu Liliana, Luță Emanuela-Alice, Biță Andrei, Corbu Alexandru Radu, Mihai Dragoș Paul, Pogan Ana Corina, Balaci Teodora Dalila, Mincă Alexandru, Duțu Ligia Elena, Olaru Octavian Tudorel, Boscencu Rica, Gîrd Cerasela Elena
Faculty of Pharmacy, University of Medicine and Pharmacy "Carol Davila", Traian Vuia 6, 020956 Bucharest, Romania.
Department of Pharmacognosy & Phytotherapy, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Petru Rareș 2, 200349 Craiova, Romania.
Biomedicines. 2024 Jun 27;12(7):1431. doi: 10.3390/biomedicines12071431.
Lipid metabolism dysregulation can lead to dyslipidemia and obesity, which are major causes of cardiovascular disease and associated mortality worldwide. The purpose of the study was to obtain and characterize six plant extracts (ACE-; RSE-; CHE-; CE-; AGE-; CGE-) as promising adjuvant therapies for the prevention and treatment of dyslipidemia and its related metabolic diseases. Phytochemical screening revealed that RSE was the richest extract in total polyphenols (39.62 ± 13.16 g tannic acid/100 g dry extract) and phenolcarboxylic acids (22.05 ± 1.31 g chlorogenic acid/100 g dry extract). Moreover, the spectrophotometric chemical profile highlighted a significant concentration of flavones for CGE (5.32 ± 0.26 g rutoside/100 g dry extract), in contrast to the other extracts. UHPLC-MS quantification detected considerable amounts of phenolic constituents, especially chlorogenic acid in CGE (187.435 ± 1.96 mg/g extract) and rosmarinic acid in RSE (317.100 ± 2.70 mg/g extract). Rosemary and hawthorn extracts showed significantly stronger free radical scavenging activity compared to the other plant extracts ( < 0.05). Pearson correlation analysis and the heatmap correlation matrix indicated significant correlations between phytochemical contents and in vitro antioxidant activities. Computational studies were performed to investigate the potential anti-obesity mechanism of the studied extracts using target prediction, homology modeling, molecular docking, and molecular dynamics approaches. Our study revealed that rosmarinic acid (RA) and chlorogenic acid (CGA) can form stable complexes with the active site of carbonic anhydrase 5A by either interacting with the zinc-bound catalytic water molecule or by directly binding Zn. Further studies are warranted to experimentally validate the predicted CA5A inhibitory activities of RA and CGA and to investigate the hypolipidemic and antioxidant activities of the proposed plant extracts in animal models of dyslipidemia and obesity.
脂质代谢失调可导致血脂异常和肥胖，而这是全球心血管疾病及相关死亡率的主要原因。本研究的目的是获取并表征六种植物提取物（ACE-；RSE-；CHE-；CE-；AGE-；CGE-），将其作为预防和治疗血脂异常及其相关代谢疾病的有前景的辅助疗法。植物化学筛选显示，RSE是总多酚（39.62±13.16克单宁酸/100克干提取物）和酚酸（22.05±1.31克绿原酸/100克干提取物）含量最丰富的提取物。此外，与其他提取物相比，分光光度化学图谱突出显示CGE中黄酮类化合物浓度显著（5.32±0.26克芦丁/100克干提取物）。超高效液相色谱-质谱定量检测到大量酚类成分，尤其是CGE中的绿原酸（187.435±1.96毫克/克提取物）和RSE中的迷迭香酸（317.100±2.70毫克/克提取物）。迷迭香和山楂提取物显示出比其他植物提取物更强的自由基清除活性（<0.05）。Pearson相关分析和热图相关矩阵表明植物化学成分与体外抗氧化活性之间存在显著相关性。使用靶点预测、同源建模、分子对接和分子动力学方法进行了计算研究，以探究所研究提取物的潜在抗肥胖机制。我们的研究表明，迷迭香酸（RA）和绿原酸（CGA）可通过与锌结合的催化水分子相互作用或直接结合锌，与碳酸酐酶5A的活性位点形成稳定复合物。有必要进行进一步研究，以实验验证RA和CGA对CA5A的预测抑制活性，并在血脂异常和肥胖动物模型中研究所提出的植物提取物的降血脂和抗氧化活性。
