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.