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

Abstract

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. Tinospora cordifolia is an illustrious Ayurveda drug, has proved juvenile and immunomodulatory properties. Twenty four (24) patients having >499mg/dL TG and 130-230mg/dL of cholesterol were randomized and given 100mL/day (~3.0g) water extract of T. cordifolia (TCE) for 14days. 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. 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 ± 9.05mg/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. T. cordifolia 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. The online version contains supplementary material available at 10.1007/s40200-022-00985-6.