Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0125)
Name
Baicalein
Synonyms
baicalein; 491-67-8; 5,6,7-Trihydroxyflavone; Noroxylin; 5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one; Biacalein; BaiKalein; 5,6,7-trihydroxy-2-phenylchromen-4-one; Baicelein; 5,6,7-trihydroxy-2-phenyl-chromen-4-one; MFCD00017459; NSC 661431; NSC-661431; CHEBI:2979; UNII-49QAH60606; NSC661431; 49QAH60606; 5,6,7-Trihydroxy-2-phenyl-4H-1-benzopyran-4-one; CHEMBL8260; 4H-1-Benzopyran-4-one, 5,6,7-trihydroxy-2-phenyl-; DTXSID2022389; 5,7-Trihydroxyflavone; BAICALEIN (USP-RS); BAICALEIN [USP-RS]; Sho-saiko-to; SMR000112462; SR-01000597499; Baicalein, 8; Baicalein,(S); 3WL; Baicalein, 14; Baicalein, 98%; Spectrum_000427; Tocris-1761; SpecPlus_000758; BAICALEIN [MI]; BAICALEIN [INCI]; Spectrum2_000466; Spectrum3_001608; Spectrum4_000537; Spectrum5_001418; BAICALEIN [WHO-DD]; Oprea1_765614; BSPBio_003215; KBioGR_001173; KBioSS_000907; MLS002473007; MLS006011756; BIDD:ER0121; DivK1c_006854; SCHEMBL139617; SPECTRUM1504002; SPBio_000572; DTXCID802389; GTPL5144; KBio1_001798; KBio2_000907; KBio2_003475; KBio2_006043; KBio3_002435; HMS1922O22; HMS2267F15; HMS3268C22; HMS3412F14; HMS3649O19; HMS3655P18; HMS3676F14; BCP14393; HY-N0196; TNP00121; BBL027840; BDBM50009001; CCG-38705; LMPK12111095; NSC729192; s2268; STL146746; AKOS005747014; AC-7991; CS-6159; NSC-729192; SDCCGMLS-0066744.P001; Baicalein, analytical reference material; SMP1_000037; NCGC00017236-01; NCGC00017236-02; NCGC00017236-03; NCGC00017236-04; NCGC00017236-05; NCGC00017236-06; NCGC00017236-07; NCGC00017236-08; NCGC00017236-10; NCGC00017236-11; NCGC00025282-01; NCGC00025282-02; NCGC00025282-03; NCGC00025282-04; NCGC00178204-01; AS-57923; PD132943; SY057137; 5,6,7-Trihydroxy-2-phenyl-chroman-4-one; FT-0622548; SW219229-1; T2721; EN300-303171; S00113; 5,7-Trihydroxy-2-phenyl-4H-1-benzopyran-4-one; A827663; Q-100550; Q2879363; SR-01000597499-1; SR-01000597499-3; SR-01000597499-4; SR-01000597499-6; W-202870; 5,6,7-Trihydroxy-2-phenyl-(4H)-1-benzopyran-4-one; BRD-K72327355-001-02-2; BRD-K72327355-001-06-3; Z1824568302

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Structure
Formula
C15H10O5
IUPAC Name
5,6,7-trihydroxy-2-phenylchromen-4-one
Canonical SMILES
C1=CC=C(C=C1)C2=CC(=O)C3=C(O2)C=C(C(=C3O)O)O
InChI
InChI=1S/C15H10O5/c16-9-6-11(8-4-2-1-3-5-8)20-12-7-10(17)14(18)15(19)13(9)12/h1-7,17-19H
InChIKey
FXNFHKRTJBSTCS-UHFFFAOYSA-N
PubChem CID
5281605
Full List of Ferroptosis Target Related to This Drug
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
 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 Marker/Suppressor
Responsed Disease Degenerative arthritis ICD-11: FA05
 Disease 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 hCDs (Chondrocytes)
In Vivo Model
C57BL/6J (WT) mice (8 weeks old, male) were purchased from Nanjing Medical university, and AMPK-KO mice were purchased from Shanghai Model Organisms. They were used to create an OA model by destabilization of the medial meniscus surgery (DMM) (n = 6 per group). Briefly, after the mice were anaesthetized, a medial articular incision was made to expose the leftjoint cavity, and then the tibial collateral ligament was transected. Finally, the articular incision was closed. In the control group, only the joint cavity was opened. One week after surgery, 1 mg/kg baicalein (MCE, HY-N0196) per knee, 1 mg/kg ML385 (MCE, HY-100523) per knee, 1 mg/kg AICAR (MCE, HY-13417) per knee or 1 mg/kg of the ferroptosis inhibitor ferrostatin-1 (Fer-1, MCE, HY-100579) was injected into the joint cavity of the mice once a week. Meanwhile, saline was injected into the control group. Mice were sacrificed after surgery 10 weeks.

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Response regulation Baicalein alleviated osteoarthritis (OA) development by improving the activity of AMPKa/Nrf2/HO-1 signaling to inhibit chondrocyte ferroptosis, revealing baicalein to be a potential therapeutic strategy for OA. AMPKa preserved Nrf2 abundance in chondrocytes and promoted Nrf2 into nucleus by promoting Keap1 degradation
Heme oxygenase 1 (HMOX1)
 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 Degenerative arthritis ICD-11: FA05
 Disease 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 hCDs (Chondrocytes)
In Vivo Model
C57BL/6J (WT) mice (8 weeks old, male) were purchased from Nanjing Medical university, and AMPK-KO mice were purchased from Shanghai Model Organisms. They were used to create an OA model by destabilization of the medial meniscus surgery (DMM) (n = 6 per group). Briefly, after the mice were anaesthetized, a medial articular incision was made to expose the leftjoint cavity, and then the tibial collateral ligament was transected. Finally, the articular incision was closed. In the control group, only the joint cavity was opened. One week after surgery, 1 mg/kg baicalein (MCE, HY-N0196) per knee, 1 mg/kg ML385 (MCE, HY-100523) per knee, 1 mg/kg AICAR (MCE, HY-13417) per knee or 1 mg/kg of the ferroptosis inhibitor ferrostatin-1 (Fer-1, MCE, HY-100579) was injected into the joint cavity of the mice once a week. Meanwhile, saline was injected into the control group. Mice were sacrificed after surgery 10 weeks.

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Response regulation Baicalein alleviated osteoarthritis (OA) development by improving the activity of AMPKa/Nrf2/HO-1 signaling to inhibit chondrocyte ferroptosis, revealing baicalein to be a potential therapeutic strategy for OA. AMPKa preserved Nrf2 abundance in chondrocytes and promoted Nrf2 into nucleus by promoting Keap1 degradation
Unspecific Target
In total 3 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Responsed Disease Traumatic brain injury ICD-11: NA07
 Disease Info 
Responsed Regulator Endoplasmic reticulum chaperone BiP (HSPA5) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model rRHs (Rat right hemispheres)
In Vivo Model
Healthy male Sprague-Dawley rats (weighing 370 g-420 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. The rats were randomized into five groups. Rats in sham group (n = 6) underwent the same anesthetic and surgical procedures, excluding cardiac arrest and CPR. All of the remaining four groups were given the interventions within 10 minutes of ROSC. Rats in CPR group (n = 6) received an intraperitoneal injection of 0.9% saline (1 mL/kg). Rats in baicalein group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein at the same time, based on previous studies. Rats in tunicamycin group (n = 6) were intraperitoneally injected with tunicamycin (2 mg/kg body weight) (22-24). Rats in baicalein + tunicamycin group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein and 2 mg/kg (body weight) tunicamycin. All groups were given the same volume of normal saline solvent (2 mL/kg).

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Response regulation Our research suggests that baicalein inhibited ferroptosis after ROSC by targeting ALOX15. Iron content, and MDA were reduced. More importantly, baicalein alleviated ER stress by inhibiting the expression of GRP78, ATF4, and CHOP. Baicalein is a potential drug to relieve brain injury after ROSC.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Responsed Disease Traumatic brain injury ICD-11: NA07
 Disease Info 
Responsed Regulator Cyclic AMP-dependent transcription factor ATF-4 (ATF4) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model rRHs (Rat right hemispheres)
In Vivo Model
Healthy male Sprague-Dawley rats (weighing 370 g-420 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. The rats were randomized into five groups. Rats in sham group (n = 6) underwent the same anesthetic and surgical procedures, excluding cardiac arrest and CPR. All of the remaining four groups were given the interventions within 10 minutes of ROSC. Rats in CPR group (n = 6) received an intraperitoneal injection of 0.9% saline (1 mL/kg). Rats in baicalein group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein at the same time, based on previous studies. Rats in tunicamycin group (n = 6) were intraperitoneally injected with tunicamycin (2 mg/kg body weight) (22-24). Rats in baicalein + tunicamycin group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein and 2 mg/kg (body weight) tunicamycin. All groups were given the same volume of normal saline solvent (2 mL/kg).

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Response regulation Our research suggests that baicalein inhibited ferroptosis after ROSC by targeting ALOX15. Iron content, and MDA were reduced. More importantly, baicalein alleviated ER stress by inhibiting the expression of GRP78, ATF4, and CHOP. Baicalein is a potential drug to relieve brain injury after ROSC.
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Responsed Disease Traumatic brain injury ICD-11: NA07
 Disease Info 
Responsed Regulator DNA damage-inducible transcript 3 protein (DDIT3) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model rRHs (Rat right hemispheres)
In Vivo Model
Healthy male Sprague-Dawley rats (weighing 370 g-420 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. The rats were randomized into five groups. Rats in sham group (n = 6) underwent the same anesthetic and surgical procedures, excluding cardiac arrest and CPR. All of the remaining four groups were given the interventions within 10 minutes of ROSC. Rats in CPR group (n = 6) received an intraperitoneal injection of 0.9% saline (1 mL/kg). Rats in baicalein group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein at the same time, based on previous studies. Rats in tunicamycin group (n = 6) were intraperitoneally injected with tunicamycin (2 mg/kg body weight) (22-24). Rats in baicalein + tunicamycin group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein and 2 mg/kg (body weight) tunicamycin. All groups were given the same volume of normal saline solvent (2 mL/kg).

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Response regulation Our research suggests that baicalein inhibited ferroptosis after ROSC by targeting ALOX15. Iron content, and MDA were reduced. More importantly, baicalein alleviated ER stress by inhibiting the expression of GRP78, ATF4, and CHOP. Baicalein is a potential drug to relieve brain injury after ROSC.
Transferrin receptor protein 1 (TFRC)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [3]
Target for Ferroptosis Marker/Suppressor/Driver
Responsed Disease Vitiligo ICD-11: ED63
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hMCs (Human mesangial cells)
Response regulation Baicalein up-regulated GPX4 and reduced TFR1 level in melanocytes treated with RSL3+FAC. Baicalein protected melanocytes against ferroptosis through up-regulating GPX4. Ferroptosis might be pervasive in the occurrence and development of vitiligo, and could be proposed as the potential therapeutic target.
Prostaglandin G/H synthase 2 (PTGS2)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [4]
Target for Ferroptosis Marker
Responsed Disease Ischemia/reperfusion injury ICD-11: DB98
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
In Vivo Model
In this study, 30 male Sprague Dawley rats (325-375 g) anesthetized using pentobarbital (1.5 g/kg, i.p.) were used for heart infarct studies,Western blot analysis, and qPCR. The isolated hearts were perfused in a Langendorff system. A water-filled latex balloon was inserted into the left ventricle cavity via mitral valve and linked to a physiological pressure transducer (AD Instruments, MLT884) for continuous monitoring of left ventricular systolic pressure (LVSP) and end diastolic pressure (LVEDP). Left ventricular developed pressure (LVDP) was calculated as the difference between LVSP and LVEDP (LVDP = LVSP-LVEDP). Measurements were recorded using PowerLab system and Chart 8 software (ADInstrument, Bella Vista, New South Wales, Australia). The hearts were stable for 30 min, and then subjected to 45 min of global ischemia by halting perfusion, followed by 1 h of reperfusion with Krebs-Henseleit (KH) bicarbonate buffer gassed with 95% O2, 5% CO2 at 37 (pH 7.4). The infarcted myocardium was measured using triphenyltetrazolium chloride(TTC, 25 mg/mL) staining. The KH buffer containing 118 mM NaCl, 4.8 mM KCl, 1.2 mM KH2PO4, 1.2 mM MgSO4, 25 mM NaHCO 31.3 mM CaCl2, and 11 mM glucose was filtered through a 0.22 uM pore before use.

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Response regulation Baicalein and luteolin protected cardiomyocytes against ferroptosis caused by ferroptosis inducers and I/R. Moreover, both baicalein and luteolin decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers. Baicalein and luteolin reduced the ischemia/reperfusion-induced myocardium infarction and decreased the levels of Acsl4 and Ptgs2 mRNA.
Polyunsaturated fatty acid lipoxygenase ALOX15 (ALOX15)
 Target Info 
In total 2 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [5]
Target for Ferroptosis Driver
Responsed Disease Status epilepticus ICD-11: 8A66
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
All adult male C57/BL6 mice weighing 18-22g were obtained from the Experimental Animal Center of Central South University, China. Animals were randomly divided into six groups as follows: 1) control group (n = 6) was given vehicle intracranial injection (PBS 5 ul); 2) FeCl3 group (n = 6) was given 5 ul 50 mM FeCl3; 3) and 4) baicalein groups were pretreated with baicalein 50 mg/kg (n = 6) and 100 mg/kg (n = 6) 30 min prior to FeCl3 administration, respectively; 5) ferroptosis inhibitor group (n = 6) was administered continuously with 10 mg/kg Lipo-1 3 d prior to FeCl3 administration; and 6) baicalein administration group (n = 6) was given 100 mg/kg baicalein once by intraperitoneal injection 30 min prior to 5 ul PBS administration.

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Response regulation Baicalein, as a naturel bioactive compound, could ameliorate behavioral seizures and play a key neuroprotective role in FeCl3-induced posttraumatic epileptic seizures through inhibiting ferroptosis and its neuroprotection might be related to suppression of 12-LOX/15-LOX.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Target for Ferroptosis Driver
Responsed Disease Traumatic brain injury ICD-11: NA07
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model rRHs (Rat right hemispheres)
In Vivo Model
Healthy male Sprague-Dawley rats (weighing 370 g-420 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. The rats were randomized into five groups. Rats in sham group (n = 6) underwent the same anesthetic and surgical procedures, excluding cardiac arrest and CPR. All of the remaining four groups were given the interventions within 10 minutes of ROSC. Rats in CPR group (n = 6) received an intraperitoneal injection of 0.9% saline (1 mL/kg). Rats in baicalein group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein at the same time, based on previous studies. Rats in tunicamycin group (n = 6) were intraperitoneally injected with tunicamycin (2 mg/kg body weight) (22-24). Rats in baicalein + tunicamycin group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein and 2 mg/kg (body weight) tunicamycin. All groups were given the same volume of normal saline solvent (2 mL/kg).

    Click to Show/Hide
Response regulation Baicalein inhibited ferroptosis after ROSC by targeting ALOX15. Iron content, and MDA were reduced. More importantly, baicalein alleviated ER stress by inhibiting the expression of GRP78, ATF4, and CHOP. Baicalein is a potential drug to relieve brain injury after ROSC.
Polyunsaturated fatty acid lipoxygenase ALOX12 (ALOX12)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [5]
Target for Ferroptosis Driver
Responsed Disease Status epilepticus ICD-11: 8A66
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
All adult male C57/BL6 mice weighing 18-22g were obtained from the Experimental Animal Center of Central South University, China. Animals were randomly divided into six groups as follows: 1) control group (n = 6) was given vehicle intracranial injection (PBS 5 ul); 2) FeCl3 group (n = 6) was given 5 ul 50 mM FeCl3; 3) and 4) baicalein groups were pretreated with baicalein 50 mg/kg (n = 6) and 100 mg/kg (n = 6) 30 min prior to FeCl3 administration, respectively; 5) ferroptosis inhibitor group (n = 6) was administered continuously with 10 mg/kg Lipo-1 3 d prior to FeCl3 administration; and 6) baicalein administration group (n = 6) was given 100 mg/kg baicalein once by intraperitoneal injection 30 min prior to 5 ul PBS administration.

    Click to Show/Hide
Response regulation Baicalein, as a naturel bioactive compound, could ameliorate behavioral seizures and play a key neuroprotective role in FeCl3-induced posttraumatic epileptic seizures through inhibiting ferroptosis and its neuroprotection might be related to suppression of 12-LOX/15-LOX.
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 4 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [6]
Target for Ferroptosis Suppressor
Responsed Disease Cerebral ischemia ICD-11: 8B10
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
The mice (23-25 g, 8-10 weeks old) were subjected to transientmiddle cerebral artery occlusion (tMCAO) to induce cerebral ischemia as previously described protocol . Briefly, mice were anesthetized with intraperitoneal injection of pentobarbital sodium (60 mg/kg) and subcutaneous injection of meloxicam (10mg/kg) during tMCAO operation. Monofilament with a silicon coating on the tip and a diameter of 0.12 mm (A5-122, Beijing Cinontech Co. Ltd., China) was inserted into the ICA from CCA to occlude the middle cerebral artery (MCA) for 1.5 h. The suture was then removed to restore blood flow for another 22.5 h reperfusion. Sham control mice were subjected to similar surgical operations without MCA occlusion. Specifically, the monofilament was inserted only 5 mm above the carotid bifurcation and withdrew immediately in the Sham group.

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Response regulation Baicalein inhibited the ferroptosis by regulating on the expression levels of GPX4, ACSL4 and ACSL3 in OGD/R cells, tMCAO mice and RSL3-stimulated HT22 cells. Our findings demonstrated that baicalein reversed the cerebral ischemia-reperfusion injury via anti-ferroptosis, which was regulated by GPX4/ACSL4/ACSL3 axis.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [4]
Target for Ferroptosis Suppressor
Responsed Disease Ischemia/reperfusion injury ICD-11: DB98
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
In Vivo Model
In this study, 30 male Sprague Dawley rats (325-375 g) anesthetized using pentobarbital (1.5 g/kg, i.p.) were used for heart infarct studies,Western blot analysis, and qPCR. The isolated hearts were perfused in a Langendorff system. A water-filled latex balloon was inserted into the left ventricle cavity via mitral valve and linked to a physiological pressure transducer (AD Instruments, MLT884) for continuous monitoring of left ventricular systolic pressure (LVSP) and end diastolic pressure (LVEDP). Left ventricular developed pressure (LVDP) was calculated as the difference between LVSP and LVEDP (LVDP = LVSP-LVEDP). Measurements were recorded using PowerLab system and Chart 8 software (ADInstrument, Bella Vista, New South Wales, Australia). The hearts were stable for 30 min, and then subjected to 45 min of global ischemia by halting perfusion, followed by 1 h of reperfusion with Krebs-Henseleit (KH) bicarbonate buffer gassed with 95% O2, 5% CO2 at 37 (pH 7.4). The infarcted myocardium was measured using triphenyltetrazolium chloride(TTC, 25 mg/mL) staining. The KH buffer containing 118 mM NaCl, 4.8 mM KCl, 1.2 mM KH2PO4, 1.2 mM MgSO4, 25 mM NaHCO 31.3 mM CaCl2, and 11 mM glucose was filtered through a 0.22 uM pore before use.

    Click to Show/Hide
Response regulation Baicalein and luteolin protected cardiomyocytes against ferroptosis caused by ferroptosis inducers and I/R. Moreover, both baicalein and luteolin decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers. Baicalein and luteolin reduced the ischemia/reperfusion-induced myocardium infarction and decreased the levels of Acsl4 and Ptgs2 mRNA.
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target [3]
Target for Ferroptosis Suppressor
Responsed Disease Vitiligo ICD-11: ED63
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hMCs (Human mesangial cells)
Response regulation Baicalein up-regulated GPX4 and reduced TFR1 level in melanocytes treated with RSL3+FAC. Baicalein protected melanocytes against ferroptosis through up-regulating GPX4. Ferroptosis might be pervasive in the occurrence and development of vitiligo, and could be proposed as the potential therapeutic target.
Experiment 4 Reporting the Ferroptosis-centered Drug Act on This Target [7]
Target for Ferroptosis Suppressor
Responsed Disease Endometriosis ICD-11: GA10
 Disease Info 
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
hMPs (Human macrophages)
Response regulation Baicalein, a potential anti-ferroptosis compound, increased GPX4 expression, significantly inhibited ferroptosis, and restored phagocytosis of THP-1 cells in vitro. Collectively, our study reveals that ferroptosis triggered by high iron in cyst fluid promotes the development of endometriosis by impairing macrophage phagocytosis and producing more angiogenic cytokines (e.g., IL8 and VEGFA).
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
 Target Info 
In total 2 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [6]
Target for Ferroptosis Driver
Responsed Disease Cerebral ischemia ICD-11: 8B10
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
The mice (23-25 g, 8-10 weeks old) were subjected to transientmiddle cerebral artery occlusion (tMCAO) to induce cerebral ischemia as previously described protocol . Briefly, mice were anesthetized with intraperitoneal injection of pentobarbital sodium (60 mg/kg) and subcutaneous injection of meloxicam (10mg/kg) during tMCAO operation. Monofilament with a silicon coating on the tip and a diameter of 0.12 mm (A5-122, Beijing Cinontech Co. Ltd., China) was inserted into the ICA from CCA to occlude the middle cerebral artery (MCA) for 1.5 h. The suture was then removed to restore blood flow for another 22.5 h reperfusion. Sham control mice were subjected to similar surgical operations without MCA occlusion. Specifically, the monofilament was inserted only 5 mm above the carotid bifurcation and withdrew immediately in the Sham group.

    Click to Show/Hide
Response regulation Baicalein inhibited the ferroptosis by regulating on the expression levels of GPX4, ACSL4 and ACSL3 in OGD/R cells, tMCAO mice and RSL3-stimulated HT22 cells. Our findings demonstrated that baicalein reversed the cerebral ischemia-reperfusion injury via anti-ferroptosis, which was regulated by GPX4/ACSL4/ACSL3 axis.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [4]
Target for Ferroptosis Driver
Responsed Disease Ischemia/reperfusion injury ICD-11: DB98
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
In Vivo Model
In this study, 30 male Sprague Dawley rats (325-375 g) anesthetized using pentobarbital (1.5 g/kg, i.p.) were used for heart infarct studies,Western blot analysis, and qPCR. The isolated hearts were perfused in a Langendorff system. A water-filled latex balloon was inserted into the left ventricle cavity via mitral valve and linked to a physiological pressure transducer (AD Instruments, MLT884) for continuous monitoring of left ventricular systolic pressure (LVSP) and end diastolic pressure (LVEDP). Left ventricular developed pressure (LVDP) was calculated as the difference between LVSP and LVEDP (LVDP = LVSP-LVEDP). Measurements were recorded using PowerLab system and Chart 8 software (ADInstrument, Bella Vista, New South Wales, Australia). The hearts were stable for 30 min, and then subjected to 45 min of global ischemia by halting perfusion, followed by 1 h of reperfusion with Krebs-Henseleit (KH) bicarbonate buffer gassed with 95% O2, 5% CO2 at 37 (pH 7.4). The infarcted myocardium was measured using triphenyltetrazolium chloride(TTC, 25 mg/mL) staining. The KH buffer containing 118 mM NaCl, 4.8 mM KCl, 1.2 mM KH2PO4, 1.2 mM MgSO4, 25 mM NaHCO 31.3 mM CaCl2, and 11 mM glucose was filtered through a 0.22 uM pore before use.

    Click to Show/Hide
Response regulation Baicalein and luteolin protected cardiomyocytes against ferroptosis caused by ferroptosis inducers and I/R. Moreover, both baicalein and luteolin decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers. Baicalein and luteolin reduced the ischemia/reperfusion-induced myocardium infarction and decreased the levels of Acsl4 and Ptgs2 mRNA.
Fatty acid CoA ligase Acsl3 (ACSL3)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [6]
Target for Ferroptosis Driver/Suppressor
Responsed Disease Cerebral ischemia ICD-11: 8B10
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
The mice (23-25 g, 8-10 weeks old) were subjected to transientmiddle cerebral artery occlusion (tMCAO) to induce cerebral ischemia as previously described protocol . Briefly, mice were anesthetized with intraperitoneal injection of pentobarbital sodium (60 mg/kg) and subcutaneous injection of meloxicam (10mg/kg) during tMCAO operation. Monofilament with a silicon coating on the tip and a diameter of 0.12 mm (A5-122, Beijing Cinontech Co. Ltd., China) was inserted into the ICA from CCA to occlude the middle cerebral artery (MCA) for 1.5 h. The suture was then removed to restore blood flow for another 22.5 h reperfusion. Sham control mice were subjected to similar surgical operations without MCA occlusion. Specifically, the monofilament was inserted only 5 mm above the carotid bifurcation and withdrew immediately in the Sham group.

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Response regulation Baicalein inhibited the ferroptosis by regulating on the expression levels of GPX4, ACSL4 and ACSL3 in OGD/R cells, tMCAO mice and RSL3-stimulated HT22 cells. Our findings demonstrated that baicalein reversed the cerebral ischemia-reperfusion injury via anti-ferroptosis, which was regulated by GPX4/ACSL4/ACSL3 axis.
References
Ref 1 Baicalein limits osteoarthritis development by inhibiting chondrocyte ferroptosis. Free Radic Biol Med. 2023 Feb 20;196:108-120. doi: 10.1016/j.freeradbiomed.2023.01.006. Epub 2023 Jan 16.
Ref 2 BAICALEIN RELIEVES BRAIN INJURY VIA INHIBITING FERROPTOSIS AND ENDOPLASMIC RETICULUM STRESS IN A RAT MODEL OF CARDIAC ARREST. Shock. 2023 Mar 1;59(3):434-441. doi: 10.1097/SHK.0000000000002058. Epub 2022 Nov 26.
Ref 3 Baicalein inhibits RLS3-induced ferroptosis in melanocytes. Biochem Biophys Res Commun. 2021 Jul 5;561:65-72. doi: 10.1016/j.bbrc.2021.05.010. Epub 2021 May 18.
Ref 4 Baicalein and luteolin inhibit ischemia/reperfusion-induced ferroptosis in rat cardiomyocytes. Int J Cardiol. 2023 Mar 15;375:74-86. doi: 10.1016/j.ijcard.2022.12.018. Epub 2022 Dec 10.
Ref 5 Baicalein Exerts Neuroprotective Effects in FeCl(3)-Induced Posttraumatic Epileptic Seizures via Suppressing Ferroptosis. Front Pharmacol. 2019 Jun 7;10:638. doi: 10.3389/fphar.2019.00638. eCollection 2019.
Ref 6 Baicalein ameliorates cerebral ischemia-reperfusion injury by inhibiting ferroptosis via regulating GPX4/ACSL4/ACSL3 axis. Chem Biol Interact. 2022 Oct 1;366:110137. doi: 10.1016/j.cbi.2022.110137. Epub 2022 Aug 31.
Ref 7 Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis. Curr Issues Mol Biol. 2022 Dec 7;44(12):6189-6204. doi: 10.3390/cimb44120422.