Kaempferol Derivatives from Hippophae rhamnoides Linn. Ameliorate H2O2‐Induced Oxidative Stress in SH‐SY5Y Cells by Upregulating Nrf2

Abstract As a medicinal and edible resource, Hippophae rhamnoides Linn. subsp. sinensis Rousi is rich in bioactive secondary metabolites, including flavonoids and their derivatives, which offer protective effects against oxidative damage. This study reported the isolation of three new kaempferol derivatives from the seed residue of H. rhamnoides – Hippophandine A, B, and C (compounds 1–3 ). Their structures were elucidated by high‐resolution electrospray ionization mass spectrometry (HR‐ESI‐MS), nuclear magnetic resonance (NMR), and chemical analyses. The compounds were evaluated for their ability to mitigate hydrogen peroxide (H 2 O 2 )‐induced cell death in SH‐SY5Y cells. The results elucidated that Hippophandine A−C at concentrations of 1, 5, and 10 μM reduced the levels of malondialdehyde (MDA) and increased the activity of antioxidative enzymes, such as superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). Furthermore, they significantly altered the protein expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and its downstream heme oxygenase‐1 (HO‐1), which is an indicator of redox detection in H 2 O 2 ‐induced SH‐SY5Y.