Antioxidant Activity of Ethanolic Litchi chinensis Seed Extract in Oxidative Stress Model Mice and Identification of Blood-Entering Prototype Components

Litchi chinensis seeds are rich in flavonoids and exhibit potent antioxidant activity. This study constructed a D-galactose-induced oxidative stress model in mice and applied ultra-high performance liquid chromatography–mass spectrometry (UHPLC-MS), network pharmacology, and molecular docking to clarify the antioxidant activity and material basis of ethanolic litchi seed extract. Litchi seed extract was orally given by gavage at 100 and 200 mg/kg in antioxidant tests, whereas a dosage of 500 mg/kg was adopted for the detection of absorbed constituents in plasma. The results showed that the total flavonoid content of litchi seed extract reached 68.37%. The extract could markedly reduce malondialdehyde (MDA) levels and elevate superoxide dismutase (SOD) activity in the serum, liver and kidney tissues of model mice, thereby mitigating oxidative damage. Thirteen prototype compounds absorbed into blood were characterized by UHPLC-MS. Most of these substances were flavonoids, with isorhamnetin, quercetin and naringenin as the major representatives. Core targets including IGF1R, PIK3R1, EGFR, PIK3CA, ERBB2 and proto-oncogene tyrosine-protein kinase Src (SRC) were screened using network pharmacology, among which SRC was identified as the pivotal hub target. Molecular docking results revealed that isorhamnetin, quercetin, naringenin, and diosmetin were able to bind stably to the SRC protein. The present study demonstrated that litchi seed extract exhibits remarkable antioxidant activity, with isorhamnetin, quercetin, naringenin, and diosmetin as the main bioactive antioxidant components.