Mechanism of drug-containing serum of Dianxianqing granules in inhibiting microglial ferroptosis
- VernacularTitle:癫痫清颗粒含药血清抑制小胶质细胞铁死亡的机制研究
- Author:
Guangkun FAN
1
;
Yue QI
2
;
Jixian WANG
1
;
Wei CHEN
3
;
Chunpeng XIA
1
;
Yihang WANG
1
;
Yue ZHAO
3
;
Yang AN
4
Author Information
1. College of Pharmacy，Liaoning University of Traditional Chinese Medicine，Liaoning Dalian 116600，China
2. Dept. of Pharmaceutical Technology，Xuzhou Medical Higher Vocational School，Jiangsu Xuzhou 221116，China
3. Dept. of Traditional Chinese Medicine Pharmacy，Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine，Shenyang 110034，China
4. Graduate School，Liaoning University of Traditional Chinese Medicine，Shenyang 110847，China
- Publication Type:Journal Article
- Keywords:
Dianxianqing granules;
mitochondrial permeability transition pore;
GSH/GPX4 pathway;
ferroptosis;
microglia
- From:
China Pharmacy
2026;37(3):317-323
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the potential mechanism by which drug-containing serum of Dianxianqing granules （DXQ） inhibits microglial ferroptosis. METHODS Male SD rats were given normal saline and Dianxianqing granules solution via intragastric administration to prepare normal serum and DXQ， respectively. Mice microglia BV2 cells were collected and successfully transfected with a negative control small interfering RNA （si-NC）， and then they were included in the si-NC group and cultured under normal conditions. Cells successfully transfected with small interfering RNA targeting glutathione peroxidase 4 （GPX4） （si-GPX4） were divided into the si-GPX4 group， the CsA group （treated with 1 μmol/L cyclosporine A）， and the DXQ- L， DXQ-M and DXQ-H groups （treated with 5%， 7% and 10% DXQ， respectively）. These groups were subsequently treated with their corresponding drug solutions and ferroptosis inducer Erastin （10 μmol/L）. The intracellular levels of total iron ions， glutathione （GSH）， reactive oxygen species （ROS）， and the expression of mitochondrial superoxide were determined in each group after 48 h of treatment. Additionally， mitochondrial membrane potential， the opening degree of mitochondrial permeability transition pore （MPTP）， and mRNA expressions of GPX4 and cyclophilin D （CypD） were detected. Furthermore， the expressions of ferroptosis-related proteins[GPX4， transferrin receptor 1 （TfR1） and ferritin heavy chain 1 （FTH1）]， as well as MPTP-related proteins [adenine nucleotide translocator （ANT）， cytochrome C （CytC）， mitochondrial calcium uniporter （MCU） and CypD] were assessed. RESULTS Compared with si-NC group， the levels of total iron ions and ROS， the expression level of mitochondrial superoxide， the opening degree of MPTP， protein and its mRNA expressions of CypD as well as protein expressions of TfR1 and MCU were increased or up-regulated significantly （P＜0.01）； however， GSH content， mitochondrial membrane potential， protein and mRNA expressions of GPX4， and protein expressions of FTH1， ANT and CytC were decreased or down-regulated significantly （P＜0.01）. Compared with the si-GPX4 group， the cells in the DXQ-M， DXQ-H groups showed a general improvement in the above quantitative indicators （P＜0.01 or P＜0.05）. CONCLUSIONS DXQ can enhance antioxidant capacity by activating the GSH/GPX4 pathway， regulate the expressions of TfR1 and FTH1 protein to correct iron ion homeostasis， inhibit excessive opening of MPTP to improve mitochondrial function， and ultimately suppress microglial ferroptosis.
