Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0289)
Name
Forsythoside A
Synonyms
Forsythoside A; Forsythiaside; 79916-77-1; Forsythiaside A; CHEMBL504363; OUH5BQ893P; CHEBI:5160; MEGxp0_001187; NSC-729638; [(2R,3S,4R,5R,6R)-6-[2-(3,4-dihydroxyphenyl)ethoxy]-4,5-dihydroxy-2-[[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxymethyl]oxan-3-yl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate; (E)-(2R,3S,4R,5R,6R)-6-(3,4-Dihydroxyphenethoxy)-4,5-dihydroxy-2-((((2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)methyl)tetrahydro-2H-pyran-3-yl 3-(3,4-dihydroxyphenyl)acrylate; AC1NQZ1W; UNII-OUH5BQ893P; Forsythoside-A; SureCN3318896; SCHEMBL3318896; ACon1_001402; DTXSID801317212; HY-N0028; BDBM50269517; MFCD08460220; NSC729638; s9317; AKOS015897128; CCG-270267; NSC 729638; NCGC00180544-01; [(2R,3S,4R,5R,6R)-6-[2-(3,4-dihydroxyphenyl)ethoxy]-4,5-dihydroxy-2-[[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-3-yl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate; beta-D-Glucopyranoside, 2-(3,4-dihydroxyphenyl)ethyl 6-O-(6-deoxy-alpha-L-mannopyranosyl)-, 4-(3-(3,4-dihydroxyphenyl)-2-propenoate), (E)-; CS-0007097; A854587; Q-100834; BRD-K62073009-001-01-6; Q27106670; (2R,3S,4R,5R,6R)-6-(3,4-dihydroxyphenethoxy)-4,5-dihydroxy-2-((((2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)methyl)tetrahydro-2H-pyran-3-yl (E)-3-(3,4-dihydroxyphenyl)acrylate; .BETA.-D-GLUCOPYRANOSIDE, 2-(3,4-DIHYDROXYPHENYL)ETHYL 6-O-(6-DEOXY-.ALPHA.-L-MANNOPYRANOSYL)-, 4-((2E)-3-(3,4-DIHYDROXYPHENYL)-2-PROPENOATE); .BETA.-D-GLUCOPYRANOSIDE, 2-(3,4-DIHYDROXYPHENYL)ETHYL 6-O-(6-DEOXY-.ALPHA.-L-MANNOPYRANOSYL)-, 4-(3-(3,4-DIHYDROXYPHENYL)-2-PROPENOATE), (E)-

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Status
Investigative
Drug Type
Small molecular drug
Structure
Formula
C29H36O15
IUPAC Name
[(2R,3S,4R,5R,6R)-6-[2-(3,4-dihydroxyphenyl)ethoxy]-4,5-dihydroxy-2-[[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxymethyl]oxan-3-yl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Canonical SMILES
CC1C(C(C(C(O1)OCC2C(C(C(C(O2)OCCC3=CC(=C(C=C3)O)O)O)O)OC(=O)C=CC4=CC(=C(C=C4)O)O)O)O)O
InChI
InChI=1S/C29H36O15/c1-13-22(35)23(36)25(38)29(42-13)41-12-20-27(44-21(34)7-4-14-2-5-16(30)18(32)10-14)24(37)26(39)28(43-20)40-9-8-15-3-6-17(31)19(33)11-15/h2-7,10-11,13,20,22-33,35-39H,8-9,12H2,1H3/b7-4+/t13-,20+,22-,23+,24+,25+,26+,27+,28+,29+/m0/s1
InChIKey
DTOUWTJYUCZJQD-UJERWXFOSA-N
PubChem CID
5281773
TTD Drug ID
D0P4JO
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 NF-kappa B signaling pathway hsa04064
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
Neuro-2a cells Neuroblastoma Mus musculus CVCL_0470
BV-2 cells Normal Mus musculus CVCL_0182
In Vivo Model
All animal experiments were approved by the Animal Ethics Committee of Jilin University (permit No. SY201905013) and were conducted in compliance with the ARRIVE guidelines. Eight-month-old B6C3-Tg (APPswePSEN1dE9)/Nju double transgenic male mice (APP/PS1) (genotype: (Appswe) T, (Psen1) T) and age-matched wild-type (WT) (genotype: (Appswe) W, (Psen1) W) male mice were purchased from Nanjing Biomedical Research Institute of Nanjing University. All mice were individually housed at 24 with food and drinking water availablead libitum. After 1 week of adaption in the new environment, WT mice received oral administration of normal saline (10 mL/kg) and were designated as the control group (n = 12). APP/PS1 mice were randomly divided into two groups: the model group (n = 12) received oral administration of normal saline (10 mL/kg) and the agent-treated group (n = 12) received oral treatment with 30 mg/kg FA (L-012-171216, 98.83% purity, Chengdu Herbpurify Co., Ltd., Chengdu, China) beginning on day 8. After 30-day treatment, behavioral experiments were serially performed. The entire treatment protocol lasted for 42 days. Blood samples were collected from the caudal vein. After euthanasia via CO2 inhalation, organs including the brain, liver, spleen, and kidney were collected for further analysis.

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Response regulation Forsythoside A treatment exerted anti-ferroptosis and anti-neuroinflammatory effects in erastin-stimulated HT22 cells, and the Nrf2/GPX4 axis played a key role in these effects. Collectively, these results demonstrate the protective effects of FA and highlight its therapeutic potential as a drug component for AD ( Alzheimer's disease) treatment.
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 Alzheimer disease ICD-11: 8A20
 Disease Info 
Pathway Response NF-kappa B signaling pathway hsa04064
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
Neuro-2a cells Neuroblastoma Mus musculus CVCL_0470
BV-2 cells Normal Mus musculus CVCL_0182
In Vivo Model
All animal experiments were approved by the Animal Ethics Committee of Jilin University (permit No. SY201905013) and were conducted in compliance with the ARRIVE guidelines. Eight-month-old B6C3-Tg (APPswePSEN1dE9)/Nju double transgenic male mice (APP/PS1) (genotype: (Appswe) T, (Psen1) T) and age-matched wild-type (WT) (genotype: (Appswe) W, (Psen1) W) male mice were purchased from Nanjing Biomedical Research Institute of Nanjing University. All mice were individually housed at 24 with food and drinking water availablead libitum. After 1 week of adaption in the new environment, WT mice received oral administration of normal saline (10 mL/kg) and were designated as the control group (n = 12). APP/PS1 mice were randomly divided into two groups: the model group (n = 12) received oral administration of normal saline (10 mL/kg) and the agent-treated group (n = 12) received oral treatment with 30 mg/kg FA (L-012-171216, 98.83% purity, Chengdu Herbpurify Co., Ltd., Chengdu, China) beginning on day 8. After 30-day treatment, behavioral experiments were serially performed. The entire treatment protocol lasted for 42 days. Blood samples were collected from the caudal vein. After euthanasia via CO2 inhalation, organs including the brain, liver, spleen, and kidney were collected for further analysis.

    Click to Show/Hide
Response regulation Forsythoside A treatment exerted anti-ferroptosis and anti-neuroinflammatory effects in erastin-stimulated HT22 cells, and the Nrf2/GPX4 axis played a key role in these effects. Collectively, these results demonstrate the protective effects of FA and highlight its therapeutic potential as a drug component for AD ( Alzheimer's disease) treatment.
References
Ref 1 Forsythoside A Mitigates Alzheimer's-like Pathology by Inhibiting Ferroptosis-mediated Neuroinflammation via Nrf2/GPX4 Axis Activation. Int J Biol Sci. 2022 Feb 28;18(5):2075-2090. doi: 10.7150/ijbs.69714. eCollection 2022.