Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0400)
Name
Tetrahydroxy stilbene glycoside
Drug Type
Traditional Chinese Medicin
Full List of Ferroptosis Target Related to This Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Alzheimer disease ICD-11: 8A20
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Pathways in cancer hsa05200
Cell Process Cell ferroptosis
In Vitro Model mHTs (Mouse hippocampus tissues)
In Vivo Model
APPswe/PSEN1dE9 (APP/PS1) double transgene mice, which were generated by the introduction of human APPswe and PS1-dE9 mutations onto the C57BL/6 background and also wild type (WT) littermates, aged 5 months, were purchased from Beijing HFK Bioscience Co., Ltd. (Beijing, China). The mice received food and water ad libitum under standard husbandry conditions (22-25, 55-65% relative humidity, and 12h/12h lightdark cycle) and acclimated 1 week for the experiments. Mice were randomly divided into 5 groups, including WT control group, APP/PS1 model group, and APP/PS1 + TSG (60, 120 and 180 mg/kg) different dosage groups. Mice were orally treated with TSG every other day for 2 months. WT and model groups were treated with equivalent vehicle.

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Response regulation Tetrahydroxy stilbene glycoside (TSG) promoted the activation of GSH/GPX4/ROS and Keap1/Nrf2/ARE signaling pathways. Notably, markers related to ferroptosis including increased lipid peroxidation, enhanced neuroinflammation such as NLRP3, and also the expression of DMT1, ACSL4 and NCOA4, were reduced by TSG administration. In addition, TSG enhanced antioxidative stress via the upregulation of SOD, and the expression of FTH1, CD98 and xCT. Hence, TSG should be taken into consideration during treatment of Alzheimer's disease in the future.
References
Ref 1 Tetrahydroxy stilbene glycoside ameliorates Alzheimer's disease in APP/PS1 mice via glutathione peroxidase related ferroptosis. Int Immunopharmacol. 2021 Oct;99:108002. doi: 10.1016/j.intimp.2021.108002. Epub 2021 Jul 29.