Insamgobonhwan Protects Neuronal Cells from Lipid ROS and Improves Deficient Cognitive Function

Iron is an essential element in the central nervous system that is involved in many of its important biological processes, such as oxygen transportation, myelin production, and neurotransmitter synthesis. Previous studies have observed the selective accumulation of iron in A beta aggregates and neurofibrillary tangles in the brains of patients with Alzheimer's disease, and excess of this accumulation is associated with accelerated cognitive decline in Alzheimer's patients. Emerging evidence suggests that ferroptosis, cell death due to iron accumulation, is a potential therapeutic target for treating Alzheimer's disease. Insamgobonhwan (GBH) is a well-regarded traditional medicine from Donguibogam that possess antioxidant properties and has been suggested to slow the aging process. However, the neuroprotective role of GBH against lipid peroxidation-induced ferroptosis and its positive cognitive effects remain unexplored. Here, we investigated the ability of GBH to protect against RSL3-induced ferroptosis in vitro and to suppress amyloid-beta-induced cognitive impairment in vivo. First, we treated HT22 cells with RSL3 to induce ferroptosis, which is an inhibitor of glutathione peroxidase 4 (GPX4) and induces lethal lipid hydroperoxide accumulation, reactive oxygen species (ROS) production, and ferroptotic cell death. GBH treatment inhibited cell death and lipid peroxidation, which were increased by RSL3 administration. In addition, GBH restored the expression of ferroptosis marker proteins, such as GPX4, HO-1 and COX-2, which were altered by RSL3. Next, we examined whether the protective ability of GBH in cells was reproduced in animals. We concluded that GBH treatment inhibited A beta-induced lipid peroxidation and improved A beta-induced cognitive impairment in mice.

Automated summary

Iron plays a crucial role in the central nervous system, being involved in important biological processes such as oxygen transportation, myelin production, and neurotransmitter synthesis. Excess accumulation of iron has been associated with accelerated cognitive decline in Alzheimer's patients. Studies suggest that ferroptosis, cell death due to iron accumulation, could be a potential therapeutic target for Alzheimer's disease. Additionally, Insamgobonhwan (GBH), a traditional medicine, has antioxidant properties and may protect against lipid peroxidation-induced ferroptosis.