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综合组学分析揭示了该干预措施对高甘油三酯血症患者多种信号通路的调节作用——一项临床试验试点。

Integrated omics analysis revealed the intervention modulated multiple signaling pathways in hypertriglyceridemia patients-a pilot clinical trial.

作者信息

Shirolkar Amey, Yadav Aarti, Nale Amit, Phogat Jatin, Dabur Rajesh

机构信息

Department of Biochemistry, National Research Institute of Basic Ayurvedic Sciences (NRIBAS), Kothrud, Pune, Maharashtra 411038 India.

Department of Biochemistry, Maharshi Dayanand University, Rohtak, Haryana 124001 India.

出版信息

J Diabetes Metab Disord. 2022 Feb 1;21(1):379-397. doi: 10.1007/s40200-022-00985-6. eCollection 2022 Jun.

Abstract

PURPOSE

Hypertriglyceridemia (HTG) is strongly associated with the various types of disease conditions and evolving as epidemics. Hence, it is important to identify molecules that lower the triglyceride and chylomicron levels. is an illustrious Ayurveda drug, has proved juvenile and immunomodulatory properties.

METHODS

Twenty four (24) patients having >499 mg/dL TG and 130-230 mg/dL of cholesterol were randomized and given 100 mL/day (~3.0 g) water extract of (TCE) for 14 days. Basal parameters were analyzed before and after TC intervention to analyzed primary outcomes. Further, unbiased metabolomics and proteomics profiling was explored to assess the efficacy of TCE in HTG patients.

RESULTS

TCE intervention decreased the levels of triglycerides, and VLDL to 380.45 ± 17.44, and 31.85 ± 5.88, and increased the HDL levels to 47.50 ± 9.05 mg/dL significantly (p < 0.05). Metabolomics analysis identified the significant alteration in 69 metabolites and 72 proteins in plasma of HTG patients. TCE intervention reduced the level of isoprostanes, ROS, BCAA, and fatty acid derivatives, significantly. The annotation databases, Metboanalyst predicted Akt and Rap1 signaling, and ECM-receptor interaction is the most affected in HTG patients. TCE intervention normalized these events by increasing the peroxisome biogenesis and modulating Akt and Rap1 signaling pathway.

CONCLUSION

intervention suppresses the baseline in HTG patients. Omics analysis showed that TCE intervention modulates the Akt and Rap signaling, and peroxisome biogenesis to control the cellular switches and signaling pathways. Hence, TCE can be used as a supplement or alternate of standard drugs being used in the management of HTG.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s40200-022-00985-6.

摘要

目的

高甘油三酯血症(HTG)与多种疾病状况密切相关且呈流行趋势。因此,识别降低甘油三酯和乳糜微粒水平的分子很重要。[药物名称]是一种著名的阿育吠陀药物,已被证明具有促生长和免疫调节特性。

方法

将24例甘油三酯(TG)>499mg/dL且胆固醇为130 - 230mg/dL的患者随机分组,给予每天100mL(约3.0g)的[药物名称]水提取物(TCE),持续14天。在TCE干预前后分析基础参数以分析主要结局。此外,进行无偏代谢组学和蛋白质组学分析以评估TCE对HTG患者的疗效。

结果

TCE干预使甘油三酯和极低密度脂蛋白(VLDL)水平分别降至380.45±17.44和31.85±5.88,并使高密度脂蛋白(HDL)水平显著升高至47.50±9.05mg/dL(p<0.05)。代谢组学分析确定了HTG患者血浆中69种代谢物和72种蛋白质有显著变化。TCE干预显著降低了异前列腺素、活性氧(ROS)、支链氨基酸(BCAA)和脂肪酸衍生物的水平。注释数据库Metboanalyst预测Akt和Rap1信号传导以及细胞外基质受体相互作用在HTG患者中受影响最大。TCE干预通过增加过氧化物酶体生物发生并调节Akt和Rap1信号通路使这些事件恢复正常。

结论

[药物名称]干预可抑制HTG患者的基线水平。组学分析表明,TCE干预调节Akt和Rap信号传导以及过氧化物酶体生物发生,以控制细胞开关和信号通路。因此,TCE可作为HTG管理中使用的标准药物的补充或替代品。

补充信息

在线版本包含可在10.1007/s40200 - 022 - 00985 - 6获取的补充材料。

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