6'-O-caffeoylarbutin attenuates D-galactose-induced brain and liver damage in aging mice via regulating SIRT1/NF-κB pathway

Background: Aging-related liver and brain damage caused by oxidative stress and inflammation significantly impacts health and quality of life. Natural bioactive compounds, such as 6'-O-caffeoylarbutin (CA), which is primarily distributed in Vaccinium species, have been studied for their antioxidant and anti-inflammatory properties. This study aims to investigate the protective effect on liver and brain damage induced by D-galactose (D-gal) in mice and to explore its potential molecular mechanisms.

Purpose: This study aims to investigate the protective effects of CA on D-galactose (D-gal)-induced liver and brain damage in mice and to explore its potential molecular mechanisms.

Methods: CA was prepared from Vaccinium dunalianum and identified using UHPLC-ESI-HR-MS/MS. Molecular docking and network pharmacology analysis were performed to predict the binding of CA with SIRT1 and NF-κB1 targets. In vivo, a D-gal-induced aging mouse model was established to evaluate the biochemical, oxidative stress, and inflammatory parameters. The effects of CA on oxidative stress and inflammation were examined through enzymatic activity assays, cytokine level measurements, and histopathological analysis. Western blotting was used to validate the involvement of the SIRT1/NF-κB pathway.

Results: CA treatment significantly alleviated liver and brain damage in D-gal-induced mice by decreasing AChE, AST, and ALT activities, improving organ indices, and reducing histopathological alterations. CA enhanced antioxidant defense by increasing SOD, CAT, and T-AOC activities, elevating GSH levels, and decreasing MDA content. Furthermore, CA suppressed the inflammatory response by downregulating IL-6 and TNF-α levels. Mechanistically, CA inhibited NF-κB p65 phosphorylation and suppressed iNOS and COX-2 expression, likely via activation of the SIRT1 protein.

Conclusion: This study demonstrates that CA protects against D-gal-induced oxidative stress and inflammation in liver and brain tissues via the SIRT1/NF-κB pathway, supporting its potential as a bioactive compound for preventing aging-related liver and brain damage.

6′-O-caffeoylarbutin; SIRT1/NF-кB signalling pathway; inflammation; network pharmacology; oxidative stress.