Berberine ameliorates iron ranges and ferroptosis within the mind of three × Tg-AD mice.
PMID:
Phytomedicine. 2023 Sep ;118:154962. Epub 2023 Jul 17. PMID: 37506403
Summary Title:
Berberine ameliorates iron ranges and ferroptosis within the mind of three × Tg-AD mice.
Summary:
BACKGROUND: Berberine (BBR) is a pure alkaloid extracted from the herb Coptis chinensis. This compound has the power to penetrate the blood-brain barrier (BBB) and exhibit neuroprotective worth within the therapy of Alzheimer’s illness (AD). AD is a neurodegenerative illness characterised byβ-amyloid (Aβ) deposition, hyperphosphorylated tau and different characters. Iron accumulation and ferroptosis had been additionally detected in AD mind, which can lead to neuronal harm. Nevertheless, it’s nonetheless unclear whether or not BBR can suppress ferroptosis in AD and alleviate its underlying pathology.PURPOSE: This examine investigated whether or not BBR might have an effect on ferroptosis and associated signaling pathways in triple transgenic AD (3 × Tg-AD) mice.METHODS: 4-month-old 3 × Tg-AD mice acquired oral administration of BBR at a dose of fifty mg/kg for 7.5 months. Cognitive operate and nervousness ranges in mice had been assessed utilizing the morris water maze take a look at, open area take a look at, and novel object recognition take a look at. Western blot, immunohistochemistry, and ICP-MS had been employed to evaluate the pathology of AD, mind iron metabolism, and ferroptosis signaling pathways. Transmission electron microscopy was used to detect mitochondrial modifications. The synergistic results of BBR mixed with Nrf2 had been investigated utilizing molecular docking packages and floor plasmon resonance expertise. Co-inmunoprecipitation assay was used to look at the impact of BBR on the binding skill of Nrf2 and Keap1.RESULTS: The outcomes indicated that continual therapy of BBR mitigated cognitive problems in 3 × Tg-AD mannequin mice. Reductions in Aβplaque, hyperphosphorylated tau protein, neuronal loss, and ferroptosis within the brains of three × Tg-AD mice steered that BBR may alleviate mind harm. As well as, BBR therapy attenuated ferroptosis, as evidenced by decreased ranges of iron, MDA, and ROS, whereas enhancing SOD, GSH, GPX4, and SLC7A11. In keeping with the in vivo assay, BBR inhibited RSL3-induced ferroptosis in N2a-sw cells. BBR elevated the expression ranges of GPX4, FPN1 and SLC7A11 by regulating Nrf2 transcription ranges, thereby inhibiting ferroptosis. Molecular docking packages and floor plasmon resonance expertise demonstrated the direct mixture of BBR with Nrf2. Co-inmunoprecipitation evaluation confirmed that BBR inhibited the interplay between Keap1 and Nrf2.CONCLUSION: For the primary time, these outcomes confirmed that BBR may inhibit iron ranges and ferroptosis within the brains of three × Tg-AD mannequin mice and partially shield towards RSL3-induced ferroptosis by way of the activation of Nrf2 signaling.
