RESUMO
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. Tinospora cordifolia 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 T. cordifolia (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: 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. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-00985-6.
RESUMO
This study was conducted to explore the antimicrobial mechanism of metabolites from Saraca asoca (SA1) using differential proteomics and metabolic profile of Pseudomonas aeruginosa after treatment with effective sub-MIC dose of 312 µg/mL. SA1 fraction was found to contain antibacterial metabolites catechol, protocatechuic acid, and epigallocatechin gallate. Proteome analysis revealed 33 differentially expressed proteins after SA1 treatment. Protein network analysis showed that SA1 treatment upregulated the DNA topological and metabolic processes. Furthermore, it revealed that T2SS, cellular component biogenesis, and response to chemical stimuli were inhibited by SA1 treatment, supported by down-regulated Na+/H+ antiporter, SdeX, ompK, and trbD proteins. Statistical analysis of mass data revealed the altered level of 20 metabolites includes HSLs, PQS, rhamnolipid, and pyocyanin. Proteome and metabolome results showed that treatment impaired cell membrane functions and quorum-sensing system. It was further confirmed by increased MDA (3.95 fold), and rhamnolipids (4.3 fold) production and, therefore, oxidative stress (36.9%) after SA1 treatment.
