Hawthorn fruit extract ameliorates H2O2-induced oxidative damage in neuronal PC12 cells and prolongs the lifespan of Caenorhabditis elegans via the IIS signaling pathway

Hawthorn (Crataegus pinnatifida) fruit has a long history of use as traditional Chinese medicine and is shown to have many health benefits including antioxidant and anti-aging. In this study, the anti-aging mechanism of hawthorn fruit extract (HFE) is predicted by network pharmacology and further verified in H₂O₂-induced PC12 cells and Caenorhabditis elegans. Network pharmacology predicted that the antiaging mechanism of HFE is mainly involved in phosphoinositide 3-kinase (PI3K)/AKT and the insulin/insulin-like growth factor-1 (IIS) signaling pathway. HFE significantly improved cell viability, increased superoxide dismutase, catalase, and glutathione peroxidase activity, decreased lactate dehydrogenase release, the level of reactive oxygen species (ROS), and malondialdehyde content in H₂O₂-induced PC12 cells (p < 0.05). HFE significantly increased the mean lifespan of C. elegans by 28.43% (100 μg mL^-1) and enhanced the stress resistance to H₂O₂, paraquat, juglone, ultraviolet radiation, and heat shock. HFE also suppressed the accumulation of aging pigments, improved the body bending ability, increased antioxidant enzyme activities, and reduced the contents of ROS and malondialdehyde. In addition, relevant gene expression, lifespan experiments with mutant strains, and molecular docking studies supported the results that HFE might extend lifespan through the IIS signal pathway.