Lipidomics Reveals the Therapeutic Effects of EtOAc Extract ofOrthosiphon stamineusBenth. on Nephrolithiasis
Lipidomics Reveals the Therapeutic Effects of EtOAc Extract ofOrthosiphon stamineusBenth. on Nephrolithiasis
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DOI：
10.3389/fphar.2020.01299
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发表时间：
2020-08-21
影响因子：
5.6
通讯作者：
Dong, Xin
中科院分区：
文献类型：
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作者：
Chao, Yufan;Gao, Songyan;Dong, Xin
背景肾结石是一种在全球范围内高发的全身性代谢性疾病，与脂质介导的氧化应激和炎症密切相关。OS是一种传统中草药，主要含有黄酮类、咖啡酸衍生物和萜类化合物，具有治疗尿路结石的作用。然而，OS治疗肾结石的有效成分及其调节机制仍不清楚。作为一种强大的抗氧化剂，草本植物中的黄酮类化合物可以通过清除自由基来减轻草酸钙结石的形成。因此，本研究以乙酸乙酯提取物(EEOS，主要为黄酮类)为研究对象，旨在揭示EEOS治疗肾结石的潜在内在机制。方法用乙酸乙酯进一步提取75%乙醇提取物，得到总黄酮含量为88.82%的乙酸乙酯提取物。其次，对提取物进行成分分析，并将其用于动物实验。采用基于超高效液相色谱-TripleTOF 5600质谱仪的非靶向脂质组学方法(UPLC-QTOF-MS)检测正常对照组、模型组和EEOS治疗组大鼠肾脏脂质变化。最后，用多元统计分析确定模型组和EEOS组小鼠血脂谱的差异。结果模型组和EEOS干预组小鼠的51种脂代谢产物有显著差异，包括甘油磷胆碱、甘油磷乙醇胺、甘油磷肌醇和甘油磷酸甘油酯。与模型组比较，EEOS组大鼠肾脏甘油磷脂酯化的omega-3多不饱和脂肪酸和甘油磷脂亚类的组成发生了明显变化。结论EEOS可通过改善甘油磷脂代谢介导的氧化应激和炎症反应抑制结石的形成。本研究从脂质分子水平揭示了EEOS治疗肾结石的可能机制，为进一步研究OS的疗效提供了新的方向。
Background Nephrolithiasis is a systemic metabolic disease with a high prevalence worldwide and is closely related to lipid-mediated oxidative stress and inflammation.Orthosiphon stamineusBenth. (OS) is a traditional medicinal herb mainly containing flavonoids, caffeic acid derivatives, and terpenoids, which has the effect of treating urinary stones. However, the active ingredients of OS for the treatment of kidney stones and their regulatory mechanisms remain unknown. As a powerful antioxidant, flavonoids from herbs can mitigate calcium oxalate stone formation by scavenging radical. Thus, this work focused on EtOAc extract of OS (EEOS, mainly flavonoids) and aimed to reveal the potential intrinsic mechanism of EEOS in the treatment of kidney stones disease. Methods Firstly, 75% ethanol extract of OS was further extracted with EtOAc to obtain EtOAc extract containing 88.82% flavonoids. Secondly, the extract was subjected to component analysis and used in animal experiments. Then, an untargeted lipidomics based on ultrahigh performance liquid chromatography coupled with TripleTOF 5600 mass spectrometer (UPLC-QTOF-MS) was performed to test the lipid changes of kidneys in the control group, model group and EEOS treatment groups. Finally, multivariate statistical analysis was used to identify differences between the lipid profiles of mice in the model group and the EEOS group. Results Fifty-one lipid metabolites were significantly different between the mice in the model group and the EEOS intervention group, including glycerophosphocholines, glycerophosphoethanolamines, glycerophosphoinositols, and glycerophosphoglycerols. And the composition of glycerophospholipids-esterified omega-3 polyunsaturated fatty acids and glycerophospholipid subclasses in the kidneys of the EEOS group significantly changed compared to model group. Conclusions The EEOS can inhibit the stones formation by improving oxidative stress and inflammation mediated by glycerophospholipid metabolism. This study reveals the potential mechanism of EEOS for kidney stones treatment at the lipid molecule level, providing a new direction for further study of the efficacy of OS.