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Huolisu Oral Liquid (HLS), a well-known traditional Chinese medicine (TCM) prescription, is an over-the-counter drug that is registered and approved by the State Food and Drug Administration (Approval No. Z51020381). HLS has been widely applied in the clinical treatment of cognitive disorders and has effects on delaying aging. The antioxidant effects of HLS are closely related to its antiaging activities, but the underlying mechanisms are unclear. In this study, the potential antioxidant ingredients of HLS were screened based on serum pharmacochemistry and network pharmacology, and the potential mechanisms involved in HLS antioxidant effects were preliminarily explored. Further, the antioxidant effects of HLS were verified by  in vivo  and  in vitro  experiments. The results showed that potential antioxidant ingredients could affect the toxic advanced glycation end products-receptor for advanced glycation end products (TAGE-RAGE) signaling, mitogen-activated protein kinase (MAPK) signaling, interleukin (IL)-17 signaling, tumor necrosis factor (TNF) signaling, toll-like receptors (TLRs), cyclic adenosine monophosphate (cAMP) signaling, hypoxia-inducible factor (HIF)-1 signaling, and other related pathways by regulating GAPDH, AKT1, TP53, MAPK1, JUN, and other associated targets. Thus, HLS may reduce inflammation, control the release of inflammatory cytokines, and regulate mitochondrial autophagy and metabolic abnormalities to ultimately play an antioxidant role. This is the first study attempting to construct a multilevel network of “HLS-antioxidant targets” based on serum pharmacochemistry and network pharmacology to explore the relationship between HLS and antioxidation and the molecular mechanisms of antioxidation combined with bioinformatics functional analysis and lays a foundation for further elucidating the antioxidant mechanisms of HLS.

The Molecular Mechanism of Antioxidation of Huolisu Oral Liquid Based on Serum Analysis and Network Analysis