Novel chlorine-containing curcumin analogue CAK06 promotes neuroprotection and rapid antidepressant through Nrf2-induced anti-inflammatory and antioxidant effects

Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00600 - e00600

Published: April 1, 2025

Currently, conventional antidepressants are often limited by poor efficacy and delayed onset, there is an urgent need for the development of rapid acting antidepressant alternatives. The aim this study was to develop novel with a onset action inhibiting inflammation oxidative stress. A series chlorine-containing curcumin analogues were designed synthesized. Among them, compound CAK06 exhibited highest potency most robust activity, as demonstrated through ABTS free radical ion scavenging assays, relative proliferation rate measurements, both hydrogen peroxide corticosterone injury models. In lipopolysaccharide-induced BV2 cell stress model, treatment resulted in 69 ​% decrease nitric oxide levels 52 reduction fluorescence intensity reactive oxygen species compared model group. qRT-PCR results showed that upregulated expression anti-inflammatory antioxidant genes while downregulating pro-inflammatory genes. CUMS depression exerted effects after 14 days oral administration. Notably, 28 days, produced more pronounced improvement depression-like behaviors widely used fluoxetine. Mechanistically, molecular docking, Western blot, Elisa indicated may alleviate stress, inflammatory responses, enhance synaptic plasticity mice via Nrf2-HO-1/BDNF-TrkB pathway. These suggest new exhibits effects, positioning it promising candidate.

Language: Английский

Physical exercise ameliorates pain, mood alterations and neuroinflammation in a murine model of osteoarthritis

Life Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 123710 - 123710

Published: May 1, 2025

Language: Английский