# Active Components of Ginkgo biloba Flower Attenuate Radiation-Induced Cognitive Impairment via Inhibiting Ferroptosis

**Authors:** Ruihong Li, Yuying Wang, Xin Sun, Ziming Xia, Ying Tian, Biqiong Chen, Shuchen Liu, Min Li, Xinlong Yan

PMC · DOI: 10.3390/antiox15020183 · Antioxidants · 2026-02-01

## TL;DR

A compound from Ginkgo biloba flowers helps protect the brain from radiation damage by preventing a type of cell death called ferroptosis.

## Contribution

The study identifies a new therapeutic candidate and a novel regulatory axis for combating ferroptosis in radiation-induced brain injury.

## Key findings

- GBF-8 administration improved cognitive function and reduced neuroinflammation in a mouse model of RBI.
- GBF-8's protective effects are linked to the inhibition of ferroptosis.
- The Slc7a11–Eif4ebp1 axis was identified as the primary target of GBF-8.

## Abstract

Radiation-induced brain injury (RBI) is a severe complication of cranial radiotherapy that poses a significant clinical challenge due to a lack of effective treatments. Ferroptosis, an oxidative stress-driven cell death pathway, has been implicated in its pathogenesis. Here, we report that 75% ethanol (GBF-8), a novel subfraction isolated from male Ginkgo biloba flowers, confers significant protection against RBI. In a murine RBI model, GBF-8 administration restored cognitive function and alleviated neuroinflammation. We demonstrated that this neuroprotective effect is mechanistically linked to ferroptosis inhibition. Integrated proteomic and metabolomic profiling identified the Solute carrier family 7 member 11 (Slc7a11)–Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (Eif4ebp1) axis as the primary target of GBF-8. This work not only establishes GBF-8 as a promising therapeutic candidate but also delineates a previously unrecognized regulatory axis for combating ferroptosis in RBI.

## Linked entities

- **Genes:** SLC7A11 (solute carrier family 7 member 11) [NCBI Gene 23657], EIF4EBP1 (eukaryotic translation initiation factor 4E binding protein 1) [NCBI Gene 1978]
- **Species:** Ginkgo biloba (taxon 3311), Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56718] {aka Frap1, RAFT1}, Akr1c6 (aldo-keto reductase family 1, member C6) [NCBI Gene 83702] {aka 3alpha-HSD, Akr1c1, Hsd17b5}, Slc7a11 (solute carrier family 7 (cationic amino acid transporter, y+ system), member 11) [NCBI Gene 26570] {aka 9930009M05Rik, sut, xCT}, Alox12 (arachidonate 12-lipoxygenase) [NCBI Gene 11684] {aka 9930022G08Rik, Alox12p, P-12LO}, Nqo1 (NAD(P)H quinone dehydrogenase 1) [NCBI Gene 24314] {aka Dia4}, Cygb (cytoglobin) [NCBI Gene 114886] {aka 3110001K20Rik, HGb, Staap}, Eif4ebp1 (eukaryotic translation initiation factor 4E binding protein 1) [NCBI Gene 116636] {aka PHAS-I}, Nox4 (NADPH oxidase 4) [NCBI Gene 50490], Sumo2 (small ubiquitin-like modifier 2) [NCBI Gene 690244] {aka Smt3A, Smt3h2}, Fth1 (ferritin heavy chain 1) [NCBI Gene 25319] {aka Fth}, Slc7a11 (solute carrier family 7 member 11) [NCBI Gene 310392], Il15 (interleukin 15) [NCBI Gene 16168] {aka IL-15}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Dcx (doublecortin) [NCBI Gene 13193] {aka Dbct}, Cxcr3 (C-X-C motif chemokine receptor 3) [NCBI Gene 12766] {aka Cd183, Cmkar3}, Arf6 (ARF GTPase 6) [NCBI Gene 11845], Ncoa4 (nuclear receptor coactivator 4) [NCBI Gene 27057] {aka ARA70, NCoA-4, Rfg}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 25125], Surf2 (surfeit 2) [NCBI Gene 619345], Braf (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 109880] {aka 9930012E13Rik, B-raf, Braf-2, Braf2, C230098H17, D6Ertd631e}, Lta (lymphotoxin A) [NCBI Gene 16992] {aka LT, LT-[a], LT-alpha, LT[a], LTalpha, Ltx}, Ireb2 (iron responsive element binding protein 2) [NCBI Gene 64602] {aka D9Ertd85e, Irp2}, Gls2 (glutaminase 2 (liver, mitochondrial)) [NCBI Gene 216456] {aka A330074B06Rik, GA, GLS, Lga}, Acsl4 (acyl-CoA synthetase long-chain family member 4) [NCBI Gene 113976] {aka Acs4, Facl4}, Slc40a1 (solute carrier family 40 (iron-regulated transporter), member 1) [NCBI Gene 53945] {aka Dusg, Fpn1, IREG1, MTP, MTP1, Ol5}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Slc1a5 (solute carrier family 1 member 5) [NCBI Gene 292657] {aka ATB(0), Asct2, H4-ASCT2, Slc1a7}, Gclc (glutamate-cysteine ligase, catalytic subunit) [NCBI Gene 14629] {aka D9Wsu168e, GLCL-H, Ggcs-hs, Glclc}, Acsl4 (acyl-CoA synthetase long-chain family member 4) [NCBI Gene 50790] {aka 9430020A05Rik, ACS4, Facl4, Lacs4}, Ccl12 (C-C motif chemokine ligand 12) [NCBI Gene 20293] {aka MCP-5, Scya12}, Bbc3 (BCL2 binding component 3) [NCBI Gene 170770] {aka PUMA, PUMA/JFY1}, Ccr3 (C-C motif chemokine receptor 3) [NCBI Gene 12771] {aka CC-CKR3, CKR3, Cmkbr1l2, Cmkbr3}, Ccl22 (C-C motif chemokine ligand 22) [NCBI Gene 20299] {aka ABCD-1, DCBCK, MDC, Scya22}, Ccl9 (C-C motif chemokine ligand 9) [NCBI Gene 20308] {aka CCF18, MRP-2, Scya10, Scya9}, Cisd2 (CDGSH iron sulfur domain 2) [NCBI Gene 67006] {aka 1500009M05Rik, 1500026J14Rik, 1500031D15Rik, B630006A20Rik, Miner1, Naf-1}, Steap3 (STEAP family member 3) [NCBI Gene 68428] {aka 1010001D01Rik, Tsap6, pHyde}, Ccl6 (C-C motif chemokine ligand 6) [NCBI Gene 20305] {aka MRP-1, Scya6, c10}, Panx2 (pannexin 2) [NCBI Gene 406218], Fth1 (ferritin heavy polypeptide 1) [NCBI Gene 14319] {aka FHC, Fth, HFt, MFH}, Alb (albumin) [NCBI Gene 11657] {aka Alb-1, Alb1, BCL001, BCL002, BPL001}, Gfap (glial fibrillary acidic protein) [NCBI Gene 14580], Il10ra (interleukin 10 receptor, alpha) [NCBI Gene 16154] {aka CDw210, CDw210a, IL-10R1, IL-10RA, Il10r, mIL-10R}
- **Diseases:** hematopoietic dysfunction (MESH:D019337), injury to (MESH:D014947), inflammation (MESH:D007249), head and neck tumors (MESH:D006258), anxiety (MESH:D001007), neuroinflammation (MESH:D000090862), B-Rapidly Accelerated Fibrosarcoma (MESH:D005354), cancer (MESH:D009369), thymic damage (MESH:D013953), Cognitive Impairment (MESH:D003072), tissue injury (MESH:D017695), IR (MESH:D011832), impaired recognition memory (MESH:D008569), LPO (MESH:D011017), Brain Injury (MESH:D001930), brain disorders (MESH:D001927), hippocampal damage (MESH:D000092223), astrogliosis (MESH:D005911), cytotoxicity (MESH:D064420), hypoactivity (MESH:D020018)
- **Chemicals:** iron (MESH:D007501), phenolic acids (MESH:C017616), DCFH-DA (MESH:C029569), terpenoids (MESH:D013729), petroleum ether (MESH:C004544), CCK-8 (MESH:D012844), water (MESH:D014867), phospholipids (MESH:D010743), ethanol (MESH:D000431), Amentoflavone (MESH:C011164), ceramide (MESH:D002518), SDS (MESH:D012967), alkaloids (MESH:D000470), formic acid (MESH:C030544), PI (MESH:D010716), glycerophospholipid (MESH:D020404), biflavonoid (MESH:D044946), Calcein-AM (MESH:C085925), Fer-1 (MESH:C573944), acetonitrile (MESH:C032159), TG (MESH:D014280), Triton X-100 (MESH:D017830), streptomycin (MESH:D013307), C3O2 (MESH:C118683), Sodium pentobarbital (MESH:D010424), polyacrylamide (MESH:C016679), polysaccharides (MESH:D011134), n- (MESH:D009584), quercetin (MESH:D011794), Chloroform (MESH:D002725), Lipid (MESH:D008055), PEs (MESH:D010714), CO2 (MESH:D002245), GSH (MESH:D005978), steroids (MESH:D013256), BCA (MESH:C047117), DMSO (MESH:D004121), flavonoids (MESH:D005419), baicalin (MESH:C038044), ROS (MESH:D017382), LysoPCs (MESH:D008244), luteolin (MESH:D047311), PVDF (MESH:C024865), 60Co (MESH:C000615395), H (MESH:D006859), PUFA (MESH:D005231), penicillin (MESH:D010406), Erastin (MESH:C477224), n-butanol (MESH:D020001), Propidium Iodide (MESH:D011419), Ethyl acetate (MESH:C007650), bilobalide (MESH:C073710), Ami (MESH:D004999), Fe2+ (-), C9H6O3 (MESH:C031477), fatty acids (MESH:D005227), PC (MESH:D010713), ginkgolides (MESH:D046934), amino acids (MESH:D000596)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Ginkgo biloba (ginkgo, species) [taxon 3311], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** PC-12 — Mus musculus (Mouse), Hybridoma (CVCL_J992), C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481)

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938514/full.md

## References

107 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938514/full.md

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Source: https://tomesphere.com/paper/PMC12938514