Integrating Structural Characterization, Network Pharmacology, and Experimental Validation Reveals the Anti-Liver Aging Mechanism of Acorus tatarinowii Polysaccharides

Liver aging is critical in chronic liver disease progression and systemic aging. Certain polysaccharides from traditional Chinese medicine have attracted increasing interest for their potential to delay liver aging. Acorus tatarinowii exhibits significant hepatoprotection, and its polysaccharides are key bioactive components against aging-related inflammation. However, the mechanism by which Acorus tatarinowii polysaccharides (ATP) protect against liver aging remains poorly understood. The structural features of ATP were characterized, and network pharmacology and bioinformatics were employed to predict key targets and pathways. Furthermore, the hepatoprotective effects of ATP were evaluated in D-galactose-induced aging rats. ATP (56.1 kDa) consisted of rhamnose, arabinose, galactose, glucose, xylose, and galacturonic acid. 272 potential targets were identified. Functional enrichment suggested that these targets were mainly involved in inflammatory response, oxidative stress, Toll-like receptor signaling, and the Keap1-Nrf2 pathway. WGCNA and machine learning identified TLR4 and Nrf2 as potential key targets. In vivo experiments showed that ATP significantly alleviated hepatic atrophy and steatosis, suppressed hepatic TLR4, NF-κB, and HO-1 expression, and activated Nrf2 expression. These findings suggest that ATP ameliorates liver aging, and its hepatoprotective effect is correlated with the regulation of the TLR4/NF-κB and Nrf2 pathways, indicating its potential as a natural anti-aging agent for liver protection.