Gut Microbiome-Associated Mechanisms of Seeraka Rasayanam in Dyslipidemia: A Systems Pharmacology Approach

Abstract

Dyslipidemia is a major metabolic disorder associated with chronic inflammation, oxidative stress, endothelial dysfunction, and cardiovascular complications. Emerging evidence suggests that gut microbiota dysbiosis plays a critical role in lipid metabolic disturbances through mechanisms involving endotoxemia, microbial metabolites, and inflammatory signaling pathways. Seeraka Rasayanam, a traditional Siddha polyherbal formulation, mentioned in Agathiyar kurunthirattu contains multiple phytochemicals with potential microbiome-modulating and anti-inflammatory properties. Objective: The present study aimed to explore the gut microbiome-associated mechanisms of Seeraka Rasayanam in dyslipidemia using a microbiome-centered systems pharmacology approach. Materials and Methods: The phytochemical constituents of Seeraka Rasayanam were identified through literature mining and phytochemical databases. Microbiome-associated phytochemicals were analyzed for their potential interactions with gut microbial communities, microbial metabolites, and host inflammatory pathways. Literature-based systems pharmacology integration was performed to identify microbiome-related signaling pathways implicated in dyslipidemia. Results: Major phytochemicals including piperine, thymoquinone, gingerol, gallic acid, plumbagin, and piperlongumine demonstrated potential associations with beneficial gut microbial populations such as lactobacillus, bifidobacterium, akkermansia and roseburia species. These interactions were linked with enhanced production of microbial metabolites including butyrate, propionate, acetate, and secondary bile acids. Integrated pathway analysis revealed potential modulation of TNF, NF-κB, IL-17, PPAR, PI3K–Akt, and AGE–RAGE signaling pathways associated with inflammation, oxidative stress, endothelial dysfunction, and lipid metabolism. Conclusion: The findings suggest that Seeraka Rasayanam may exert anti-dyslipidemic effects through modulation of gut microbiota-associated inflammatory and metabolic pathways. The proposed microbiome-centered systems pharmacology framework provides a mechanistic basis for future experimental validation of Siddha formulations in metabolic disorders.