Rosa chinensis cv. 'JinBian' flowers alleviates brain damage and cognitive deficit by inhibiting ferroptosis via the Keap1/Nrf2/GPX4 pathway and regulating gut microbiota.

The ethyl acetate fraction (RE) had the highest phenolic and flavonoid contents and strongest antioxidant scavenging capacities among all RCF fractions.

• Four fractions were obtained from RCF via liquid-liquid extraction: dichloromethane (RD), ethyl acetate (RE), n-butanol (RB), and residual water (RW)
• RE exhibited the strongest ABTS⁺ and DPPH⁺ scavenging capacities compared to the other fractions
• RE had the highest total phenolic and total flavonoid contents among all fractions tested

UHPLC-ESI-HRMS/MS analysis identified 28 phytochemicals in RE, primarily gallic acid derivatives and flavonoid derivatives.

• Analysis was performed using ultra-high performance liquid chromatography electrospray ionization high-resolution tandem mass spectrometry (UHPLC-ESI-HRMS/MS)
• The 28 identified phytochemicals were primarily categorized as gallic acid derivatives and flavonoid derivatives
• RCF has been noted to be enriched in flavonoids and exhibits significant antioxidant effects

RE significantly inhibited ROS accumulation and increased antioxidant enzyme activities in H₂O₂-induced SH-SY5Y cells.

• In vitro assays used H₂O₂-induced SH-SY5Y neuroblastoma cells as a model
• RE treatment increased antioxidant markers including GSH (glutathione), CAT (catalase), and SOD (superoxide dismutase)
• RE significantly inhibited reactive oxygen species (ROS) accumulation in the oxidatively stressed neuronal cells

RE alleviated memory impairment and anxiety-like behavior in D-galactose-induced aging mice.

• In vivo model used D-galactose-induced mice to simulate aging-related cognitive decline
• Behavioral assessments included the Morris water maze test (spatial memory) and the crucifixion anxiety test (anxiety-like behavior)
• RE treatment ameliorated both memory impairment and anxiety-like behavior compared to the D-galactose model group

RE activated the Keap1/Nrf2-regulated antioxidant pathway and suppressed ferroptosis in D-galactose-induced mice.

• RE treatment increased total antioxidant capacity (T-AOC), GSH, GPX4, NQO1, SOD1, and HO-1 in brain tissue
• Upregulation of GPX4 is a key indicator of ferroptosis suppression, as GPX4 is a central regulator of ferroptotic cell death
• The mechanism was identified as operating via the Keap1/Nrf2/GPX4 pathway

RE attenuated neuronal apoptosis through inhibition of the GSK-3β/Tau/Bcl-2 signaling axis in D-galactose-induced mice.

• RE treatment modulated the GSK-3β/Tau/Bcl-2 axis-regulated apoptosis pathway
• RE also inhibited acetylcholinesterase (AChE) activity, which is relevant to cholinergic neurotransmission and cognitive function
• Modulation of AMPK-regulated autophagy was also observed alongside the apoptosis findings

RE improved gut microbiota diversity in D-galactose-induced aging mice, particularly increasing beneficial bacteria.

• RE treatment increased the abundance of beneficial bacteria including Lactobacillus and Bifidobacterium
• Overall gut microbiota diversity was improved following RE treatment
• Gut microbiota modulation was identified as an additional mechanism through which RE exerts neuroprotective effects