Tenuifolin in the prevention of Alzheimer's disease-like phenotypes: Investigation of the mechanisms from the perspectives of calpain system, ferroptosis, and apoptosis

by Selleckchem | Oct 26 2023

Polygala tenuifolia was documented to calm the mind and promote wisdom. However, its underlying mechanisms are still unclear. This study aimed to investigate the mechanisms underlying the effects of tenuifolin (Ten) on Alzheimer's disease (AD)-like phenotypes. We first applied bioinformatics methods to screen the mechanisms of P. tenuifolia in the treatment of AD. Thereafter, the d-galactose combined with Aβ1-42 (GCA) was applied to model AD-like behaviors and investigate the action mechanisms of Ten, one active component of P. tenuifolia. The data showed that P. tenuifolia actioned through multi-targets and multi-pathways, including regulation of synaptic plasticity, apoptosis, and calcium signaling, and so forth. Furthermore, in vitro experiments demonstrated that Ten prevented intracellular calcium overload, abnormal calpain system, and down-regulation of BDNF/TrkB signaling induced by GCA. Moreover, Ten suppressed oxidative stress and ferroptosis in HT-22 cells induced by GCA. Calpeptin and ferroptosis inhibitor prevented the decrease of cell viability induced by GCA. Interestingly, calpeptin did not interrupt GCA-induced ferroptosis in HT-22 cells but blocked the apoptosis. Animal experiments further demonstrated that Ten prevented GCA-induced memory impairment in mice and increased synaptic protein expression while reducing m-calpain expression. Ten prevents AD-like phenotypes through multiple signaling by inhibiting oxidative stress and ferroptosis, maintaining the stability of calpain system, and suppressing neuronal apoptosis.

Comments:

The study you mentioned aimed to investigate the mechanisms underlying the effects of tenuifolin (Ten), an active component of Polygala tenuifolia, on Alzheimer's disease (AD)-like phenotypes. The researchers used bioinformatics methods to screen the mechanisms of P. tenuifolia in the treatment of AD. They then employed a combination of d-galactose and Aβ1-42 (GCA) to model AD-like behaviors and study the action mechanisms of Ten.

The data from the study indicated that P. tenuifolia exerts its effects through multiple targets and pathways, including the regulation of synaptic plasticity, apoptosis, and calcium signaling, among others. In vitro experiments demonstrated that Ten prevented intracellular calcium overload, abnormal calpain system activity, and down-regulation of BDNF/TrkB signaling induced by GCA.

Furthermore, Ten was found to suppress oxidative stress and ferroptosis in HT-22 cells induced by GCA. The researchers also observed that calpeptin, a calpain inhibitor, and a ferroptosis inhibitor prevented the decrease in cell viability induced by GCA. Interestingly, calpeptin did not interfere with GCA-induced ferroptosis in HT-22 cells but blocked apoptosis.

Animal experiments conducted as part of the study further demonstrated that Ten prevented GCA-induced memory impairment in mice. It also increased the expression of synaptic proteins while reducing m-calpain expression. These findings suggest that Ten prevents AD-like phenotypes through multiple signaling pathways by inhibiting oxidative stress and ferroptosis, maintaining the stability of the calpain system, and suppressing neuronal apoptosis.

In summary, the study provides insights into the potential mechanisms underlying the beneficial effects of Ten, an active component of P. tenuifolia, on AD-like phenotypes. It suggests that Ten acts through multiple targets and pathways, including synaptic plasticity, apoptosis, calcium signaling, oxidative stress, and ferroptosis, to prevent memory impairment and promote neuronal health in the context of AD.