Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00075)
Name
Subarachnoid Hemorrhage
ICD
ICD-11: 8B01
Full List of Target(s) of This Ferroptosis-centered Disease
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Subarachnoid hemorrhage [ICD-11: 8B01]
Responsed Drug Astragaloside IV Investigative
 Drug Info 
Responsed Regulator Kelch-like ECH-associated protein 1 (KEAP1) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model hBCs (Brain cells)
In Vivo Model
SAH model was constructed by applying endovascular perforation in the rats, according to the protocol introduced in a previous study (Wei et al., 2020), except for slight modifications. Briefly, after performing intraperitoneal anesthesia with 40 mg/kg sodium pentobarbital, the right common carotid, external and internal carotid arteries of the rats were exposed and isolated. The right external carotid artery was ligated, and a 4-0 single-strand nylon thread was used to insert the right internal carotid artery through the stump of the external carotid artery and the bifurcation of the common carotid artery. When resistance is felt when the suture enters the intracranial segment, proceed approximately 3 mm to penetrate internal carotid artery at the bifurcation of middle cerebral artery. The suture was held in this position for 10 s and was then withdrawn. The rats in the Sham group went through an identical procedure, without the suture at the point of resistance. Throughout the experiment, the body temperature of the rats was sustained at around 37 by using a thermal blanket. After the wounds were sutured, the rats were placed in a separate cage and neurological function was closely observed.

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Response regulation Astragaloside IV (AS-IV) triggered Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of subarachnoid hemorrhage (SAH). The Nrf2 inhibitor ML385 blocked the beneficial effects of neuroprotection. Ferroptosis is profoundly implicated in facilitating EBI in SAH, and that AS-IV thwarts the process of ferroptosis in SAH by activating Nrf2/HO-1 pathway. The liberation of Nrf2 from Keap1, its cytoplasmic repressor will provoke Nrf2 accumulation in the nucleus.
Heme oxygenase 1 (HMOX1)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Subarachnoid hemorrhage [ICD-11: 8B01]
Responsed Drug Astragaloside IV Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model hBCs (Brain cells)
In Vivo Model
SAH model was constructed by applying endovascular perforation in the rats, according to the protocol introduced in a previous study (Wei et al., 2020), except for slight modifications. Briefly, after performing intraperitoneal anesthesia with 40 mg/kg sodium pentobarbital, the right common carotid, external and internal carotid arteries of the rats were exposed and isolated. The right external carotid artery was ligated, and a 4-0 single-strand nylon thread was used to insert the right internal carotid artery through the stump of the external carotid artery and the bifurcation of the common carotid artery. When resistance is felt when the suture enters the intracranial segment, proceed approximately 3 mm to penetrate internal carotid artery at the bifurcation of middle cerebral artery. The suture was held in this position for 10 s and was then withdrawn. The rats in the Sham group went through an identical procedure, without the suture at the point of resistance. Throughout the experiment, the body temperature of the rats was sustained at around 37 by using a thermal blanket. After the wounds were sutured, the rats were placed in a separate cage and neurological function was closely observed.

    Click to Show/Hide
Response regulation Astragaloside IV (AS-IV) triggered Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of subarachnoid hemorrhage (SAH). The Nrf2 inhibitor ML385 blocked the beneficial effects of neuroprotection. These results consistently suggest that ferroptosis is profoundly implicated in facilitating EBI in SAH, and that AS-IV thwarts the process of ferroptosis in SAH by activating Nrf2/HO-1 pathway.
References
Ref 1 Astragaloside IV attenuates ferroptosis after subarachnoid hemorrhage via Nrf2/HO-1 signaling pathway. Front Pharmacol. 2022 Aug 19;13:924826. doi: 10.3389/fphar.2022.924826. eCollection 2022.