[1] Zhao YP, et al. Resequencing 545 ginkgo genomes across the world reveals the evolutionary history of the living fossil. Nat Commun. 2019;10(1):4201.
[2] McKenna DJ, Jones K, Hughes K. Efficacy, safety, and use of Ginkgo biloba in clinical and preclinical applications. Altern Ther Health Med. 2001;7(5):70-86.
[3] Chen Y, et al. Ginkgo biloba. Trends Genet. 2021;37(5):488-9.
[4] Boateng ID. Ginkgols and bilobols in Ginkgo biloba L. a review of their extraction and bioactivities. Phytother Res. 2023;37(8):3211-23.
[5] Guo J, et al. Overview and recent progress on the biosynthesis and regulation of flavonoids in Ginkgo biloba L. Int J Mol Sci. 2023. https://doi.org/10.3390/ijms241914604.
[6] Mohammadi Zonouz A, Ghasemzadeh Rahbardar M, Hosseinzadeh H. The molecular mechanisms of ginkgo (Ginkgo biloba) activity in signaling pathways: a comprehensive review. Phytomedicine. 2024;126: 155352.
[7] Shareena G, Kumar D. Traversing through half a century research timeline on Ginkgo biloba, in transforming a botanical rarity into an active functional food ingredient. Biomed Pharmacother. 2022;153: 113299.
[8] Omidkhoda SF, Razavi BM, Hosseinzadeh H. Protective effects of Ginkgo biloba L. against natural toxins, chemical toxicities, and radiation: a comprehensive review. Phytother Res. 2019;33(11):2821-40.
[9] Boateng ID. A critical review of current technologies used to reduce ginkgotoxin, ginkgotoxin-5’-glucoside, ginkgolic acid, allergic glycoprotein, and cyanide in Ginkgo biloba L. seed. Food Chem. 2022;382: 132408.
[10] Trabert M, Seifert R. Critical analysis of ginkgo preparations: comparison of approved drugs and dietary supplements marketed in Germany. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(1):451-61.
[11] Su X, et al. Medicinal values and potential risks evaluation of Ginkgo biloba leaf extract (GBE) drinks made from the leaves in autumn as dietary supplements. Molecules. 2022. https://doi.org/10.3390/molecules27217479.
[12] Yuan C, et al. Efficacy and safety of Ginkgo biloba extract as an adjuvant in the treatment of Chinese patients with sudden hearing loss: a meta-analysis. Pharm Biol. 2023;61(1):610-20.
[13] Asiwe JN, et al. Ginkgo biloba supplement modulates mTOR/ERK1/2 activities to mediate cardio-protection in cyclosporin-A-induced cardiotoxicity in Wistar rats. Clin Tradit Med Pharmacol. 2024;5(1): 200134.
[14] Yu J, et al. New insight into the mechanisms of Ginkgo biloba leaves in the treatment of cancer. Phytomedicine. 2024;122: 155088.
[15] Lu J, et al. Hyperspectral imaging combined with deep transfer learning to evaluate flavonoids content in Ginkgo biloba leaves. Int J Mol Sci. 2024. https://doi.org/10.3390/ijms25179584.
[16] Mao D, et al. Function, biosynthesis, and regulation mechanisms of flavonoids in Ginkgo biloba. Fruit Res. 2023. https://doi.org/10.48130/FruRes-2023-0018.
[17] Li X, et al. 3’,8″-dimerization enhances the antioxidant capacity of flavonoids: evidence from acacetin and isoginkgetin. Molecules. 2019. https://doi.org/10.3390/molecules24112039.
[18] Kovač Tomas M, Jurčević I, Šamec D. Tissue-specific profiling of biflavonoids in Ginkgo (Ginkgo biloba L.). Plants. 2022. https://doi.org/10.3390/plants12010147.
[19] Sagrera G, et al. Synthesis and antifungal activities of natural and synthetic biflavonoids. Bioorg Med Chem. 2011;19(10):3060-73.
[20] Tao Z, et al. Therapeutic effect of ginkgetin on smoke-induced airway inflammation by down-regulating the c/EBPβ signaling pathway and CCL2 expression. J Ethnopharmacol. 2024;331: 118284.
[21] Hu B, et al. Ginkgetin alleviates intervertebral disc degeneration by inhibiting apoptosis, inflammation, and disturbance of extracellular matrix synthesis and catabolism via inactivation of NLRP3 inflammasome. Immunol Invest. 2023;52(5):546-60.
[22] Li G, et al. Ginkgetin in vitro and in vivo reduces Streptococcus suis virulence by inhibiting suilysin activity. J Appl Microbiol. 2019;127(5):1556-63.
[23] Menezes J, Campos VR. Natural biflavonoids as potential therapeutic agents against microbial diseases. Sci Total Environ. 2021;769: 145168.
[24] Castañeda P, et al. Effects of some compounds isolated fromCelaenodendron mexicanum standl (euphorbiaceae) on seeds and phytopathogenic fungi. J Chem Ecol. 1992;18(7):1025-37.
[25] Jurčević Šangut I, et al. A comparative analysis of radical scavenging, antifungal and enzyme inhibition activity of 3’-8″-biflavones and their monomeric subunits. Antioxidants. 2023. https://doi.org/10.3390/antiox12101854.
[26] Patel CN, et al. Computational investigation of natural compounds as potential main protease [M(pro)] inhibitors for SARS-CoV-2 virus. Comput Biol Med. 2022;151(Pt A): 106318.
[27] Sharma S, et al. Avocado-derived extracellular vesicles loaded with ginkgetin and berberine prevent inflammation and macrophage foam cell formation. J Cell Mol Med. 2024;28(7): e18177.
[28] Wang LT, et al. Biflavonoids from Ginkgo biloba leaves as a novel anti-atherosclerotic candidate: inhibition potency and mechanistic analysis. Phytomedicine. 2022;102: 154053.
[29] Cho YL, et al. Ginkgetin, a biflavone from Ginkgo biloba leaves, prevents adipogenesis through STAT5-mediated PPARγ and C/EBPα regulation. Pharmacol Res. 2019;139:325-36.
[30] Akbar A, Ijaz MU. Pharmacotherapeutic potential of ginkgetin against polystyrene microplastics-instigated testicular toxicity in rats: a biochemical, spermatological, and histopathological assessment. Environ Sci Pollut Res Int. 2024;31(6):9031-44.
[31] Yamaguchi LF, et al. Biflavonoids from Brazilian pine Araucaria angustifolia as potentials protective agents against DNA damage and lipoperoxidation. Phytochemistry. 2005;66(18):2238-47.
[32] Liu Y, et al. Ginkgetin alleviates inflammation and senescence by targeting STING. Adv Sci (Weinh). 2024. https://doi.org/10.1002/advs.202407222.
[33] Smer-Barreto V, et al. Discovery of senolytics using machine learning. Nat Commun. 2023;14(1):3445.
[34] Ren G, et al. Modulation of Bleomycin-induced oxidative stress and pulmonary fibrosis by Ginkgetin in mice via AMPK. Curr Mol Pharmacol. 2023;16(2):217-27.
[35] Wang C, et al. Ginkgetin exhibits antifibrotic effects by inducing hepatic stellate cell apoptosis via STAT1 activation. Phytother Res. 2024;38(3):1367-80.
[36] Tatlı Çankaya I, et al. Neuroprotective potential of biflavone Ginkgetin: a review. Life. 2023. https://doi.org/10.3390/life13020562.
[37] Tian Z, Tang C, Wang Z. Neuroprotective effect of ginkgetin in experimental cerebral ischemia/reperfusion via apoptosis inhibition and PI3K/Akt/mTOR signaling pathway activation. J Cell Biochem. 2019;120(10):18487-95.
[38] Jeon YJ, et al. Ginkgetin inhibits the growth of DU-145 prostate cancer cells through inhibition of signal transducer and activator of transcription 3 activity. Cancer Sci. 2015;106(4):413-20.
[39] Sun CM, et al. Selective cytotoxicity of ginkgetin from Selaginella moellendorffii. J Nat Prod. 1997;60(4):382-4.
[40] Adnan M, et al. Ginkgetin: a natural biflavone with versatile pharmacological activities. Food Chem Toxicol. 2020;145: 111642.
[41] Park Y, et al. Ginkgetin induces cell death in breast cancer cells via downregulation of the estrogen receptor. Oncol Lett. 2017;14(4):5027-33.
[42] Cao J, et al. Ginkgetin inhibits growth of breast carcinoma via regulating MAPKs pathway. Biomed Pharmacother. 2017;96:450-8.
[43] Duan Q, et al. Ginkgetin enhances breast cancer radiotherapy sensitization by suppressing NRF2-HO-1 axis activity. Toxicol Appl Pharmacol. 2025;495: 117199.
[44] Alu A, et al. Ginkgo biloba derivative ginkgetin inhibits breast cancer growth by regulating the miRNA-122-5p/GALNT10 axis. Chin Med J (Engl). 2024;137(19):2387-9.
[45] Su Y, et al. Studies on the cytotoxic mechanisms of ginkgetin in a human ovarian adenocarcinoma cell line. Naunyn Schmiedebergs Arch Pharmacol. 2000;362(1):82-90.
[46] Cheng J, Li Y, Kong J. Ginkgetin inhibits proliferation of HeLa cells via activation of p38/NF-κB pathway. Cell Mol Biol (Noisy-le-grand). 2019;65(4):79-82.
[47] Lee YJ, et al. Ginkgetin induces G2-phase arrest in HCT116 colon cancer cells through the modulation of b-Myb and miRNA34a expression. Int J Oncol. 2017;51(4):1331-42.
[48] Zhang S, et al. Ginkgo biflavones cause p53 wild-type dependent cell death in a transcription-independent manner of p53. J Nat Prod. 2023;86(2):346-56.
[49] Liu Q, et al. Anti-tumor effect of ginkgetin on human hepatocellular carcinoma cell lines by inducing cell cycle arrest and promoting cell apoptosis. Cell Cycle. 2022;21(1):74-85.
[50] Ren Y, et al. Ginkgetin induces apoptosis in 786-O cell line via suppression of JAK2-STAT3 pathway. Iran J Basic Med Sci. 2016;19(11):1245-50.
[51] Pan LL, et al. Corrigendum to: Ginkgetin inhibits proliferation of human leukemia cells via the TNF-α signaling pathway. Z Naturforsch C J Biosci. 2017;72(11-12):507.
[52] Baek SH, et al. Ginkgetin blocks constitutive STAT3 activation and induces apoptosis through induction of SHP-1 and PTEN tyrosine phosphatases. Phytother Res. 2016;30(4):567-76.
[53] Liu K, et al. Integrating network pharmacology prediction and experimental investigation to verify ginkgetin anti-invasion and metastasis of human lung adenocarcinoma cells via the Akt/GSK-3β/Snail and Wnt/β-catenin pathway. Front Pharmacol. 2023;14:1135601.
[54] Lou JS, et al. Ginkgetin induces autophagic cell death through p62/SQSTM1-mediated autolysosome formation and redox setting in non-small cell lung cancer. Oncotarget. 2017;8(54):93131-48.
[55] Sun L, et al. Ginkgetin inhibits the proliferation and migration of lung cancer cells via FAK/STAT3/AKT pathway. Mol Biol Rep. 2025;52(1):458.
[56] Ye ZN, et al. Biflavone Ginkgetin, a novel Wnt inhibitor, suppresses the growth of medulloblastoma. Nat Prod Bioprospect. 2015;5(2):91-7.
[57] Liu L, et al. Structure-based discovery of Licoflavone B and Ginkgetin targeting c-Myc G-quadruplex to suppress c-Myc transcription and myeloma growth. Chem Biol Drug Des. 2022;100(4):525-33.
[58] Xiong M, et al. Ginkgetin exerts growth inhibitory and apoptotic effects on osteosarcoma cells through inhibition of STAT3 and activation of caspase-3/9. Oncol Rep. 2016;35(2):1034-40.
[59] Wu L, et al. Ginkgetin suppresses ovarian cancer growth through inhibition of JAK2/STAT3 and MAPKs signaling pathways. Phytomedicine. 2023;116: 154846.
[60] You OH, et al. Ginkgetin induces apoptosis via activation of caspase and inhibition of survival genes in PC-3 prostate cancer cells. Bioorg Med Chem Lett. 2013;23(9):2692-5.
[61] Lou JS, et al. Ginkgetin derived from Ginkgo biloba leaves enhances the therapeutic effect of cisplatin via ferroptosis-mediated disruption of the Nrf2/HO-1 axis in EGFR wild-type non-small-cell lung cancer. Phytomedicine. 2021;80: 153370.
[62] Hu WH, et al. Synergy of Ginkgetin and resveratrol in suppressing VEGF-induced angiogenesis: a therapy in treating colorectal cancer. Cancers (Basel). 2019. https://doi.org/10.3390/cancers11121828.
[63] Patra D, et al. Anti-cancer drug molecules targeting cancer cell cycle and proliferation. Adv Protein Chem Struct Biol. 2023;135:343-95.
[64] Suski JM, et al. Targeting cell-cycle machinery in cancer. Cancer Cell. 2021;39(6):759-78.
[65] Ren Y, Kinghorn AD. Development of potential antitumor agents from the scaffolds of plant-derived terpenoid lactones. J Med Chem. 2020;63(24):15410-48.
[66] Kim KH, et al. Different apoptotic effects of saxifragifolin C in human breast cancer cells. Arch Pharm Res. 2016;39(4):577-89.
[67] Vethakanraj HS, et al. Anticancer effect of acid ceramidase inhibitor ceranib-2 in human breast cancer cell lines MCF-7, MDA MB-231 by the activation of SAPK/JNK, p38 MAPK apoptotic pathways, inhibition of the Akt pathway, downregulation of ERα. Anticancer Drugs. 2018;29(1):50-60.
[68] Kim KH, et al. Different anticancer effects of Saxifragifolin A on estrogen receptor-positive and estrogen receptor-negative breast cancer cells. Phytomedicine. 2015;22(9):820-8.
[69] Debnath J, Gammoh N, Ryan KM. Autophagy and autophagy-related pathways in cancer. Nat Rev Mol Cell Biol. 2023;24(8):560-75.
[70] Li X, He S, Ma B. Autophagy and autophagy-related proteins in cancer. Mol Cancer. 2020;19(1):12.
[71] Zhang LL, et al. Phanginin R induces cytoprotective autophagy via JNK/c-Jun signaling pathway in non-small cell lung cancer A549 cells. Anticancer Agents Med Chem. 2020;20(8):982-8.
[72] Pan J, et al. Ginkgetin attenuates cerebral ischemia-reperfusion induced autophagy and cell death via modulation of the NF-κB/p53 signaling pathway. 2019. Biosci Rep. https://doi.org/10.1042/BSR20191452.
[73] Wei L, et al. Ginkgetin alleviates high glucose-evoked mesangial cell oxidative stress injury, inflammation, and extracellular matrix (ECM) deposition in an AMPK/mTOR-mediated autophagy axis. Chem Biol Drug Des. 2021;98(4):620-30.
[74] Liu J, et al. Selective autophagy in cancer: mechanisms, therapeutic implications, and future perspectives. Mol Cancer. 2024;23(1):22.
[75] Yuan R, et al. Natural products to prevent drug resistance in cancer chemotherapy: a review. Ann N Y Acad Sci. 2017;1401(1):19-27.
[76] Niu X, et al. Autophagy in cancer development, immune evasion, and drug resistance. Drug Resist Updat. 2025;78: 101170.
[77] Poillet-Perez L, Sarry JE, Joffre C. Autophagy is a major metabolic regulator involved in cancer therapy resistance. Cell Rep. 2021;36(7): 109528.
[78] Lei G, Zhuang L, Gan B. Targeting ferroptosis as a vulnerability in cancer. Nat Rev Cancer. 2022;22(7):381-96.
[79] Newton K, et al. Cell death. Cell. 2024;187(2):235-56.
[80] Mokhtari Tabar MM, et al. Computational discovery of novel GPX4 inhibitors from herbal sources as potential ferroptosis inducers in cancer therapy. Arch Biochem Biophys. 2024;764: 110231.
[81] Wang HJ, et al. TFEB promotes Ginkgetin-induced ferroptosis via TRIM25 mediated GPX4 lysosomal degradation in EGFR wide-type lung adenocarcinoma. Theranostics. 2025;15(7):2991-3012.
[82] Kang R, Kroemer G, Tang D. The tumor suppressor protein p53 and the ferroptosis network. Free Radic Biol Med. 2019;133:162-8.
[83] Liu ZL, et al. Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Signal Transduct Target Ther. 2023;8(1):198.
[84] Cao Y, Langer R, Ferrara N. Targeting angiogenesis in oncology, ophthalmology and beyond. Nat Rev Drug Discov. 2023;22(6):476-95.
[85] Bahar ME, Kim HJ, Kim DR. Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies. Signal Transduct Target Ther. 2023;8(1):455.
[86] de Almeida LGN, et al. Matrix metalloproteinases: from molecular mechanisms to physiology, pathophysiology, and pharmacology. Pharmacol Rev. 2022;74(3):712-68.
[87] Fontana R, Mestre-Farrera A, Yang J. Update on epithelial-mesenchymal plasticity in cancer progression. Annu Rev Pathol. 2024;19:133-56.
[88] Cordani M, et al. Signaling, cancer cell plasticity, and intratumor heterogeneity. Cell Commun Signal. 2024;22(1):255.
[89] Huang Y, Hong W, Wei X. The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis. J Hematol Oncol. 2022;15(1):129.
[90] Jiang X, et al. Recent advances in identifying protein targets of bioactive natural products. Heliyon. 2024;10(13): e33917.
[91] Bhadresha K, et al. Computational investigation of ginkgetin and theaflavin as potential inhibitors of heat shock protein 90 (Hsp90). J Biomol Struct Dyn. 2022;40(24):13675-81.
[92] Kim HP, et al. Biochemical pharmacology of biflavonoids: implications for anti-inflammatory action. Arch Pharm Res. 2008;31(3):265-73.
[93] Chen J, et al. Conditional sequential delivery of ginkgetin and rapamycin orchestrates inflammation and autophagy to alleviate intervertebral disc degeneration. J Control Release. 2025;381: 113556.
[94] Xiong X, et al. Insights into Amentoflavone: a natural multifunctional biflavonoid. Front Pharmacol. 2021;12: 768708.
[95] Feng Y, et al. Preparation of amentoflavone-loaded DSPE-PEG(2000) micelles with improved bioavailability and in vitro antitumor efficacy. Biomed Chromatogr. 2023;37(9): e5690.
[96] Wang B, et al. Potent inhibition of human cytochrome P450 3A4 by biflavone components from Ginkgo biloba and Selaginella tamariscina. Front Pharmacol. 2022;13: 856784.
[97] Li YY, et al. Potential hepatic and renal toxicity induced by the biflavonoids from Ginkgo biloba. Chin J Nat Med. 2019;17(9):672-81.
[98] Pang HL, et al. Discovery and characterization of the key constituents in Ginkgo biloba leaf extract with potent inhibitory effects on human UDP-glucuronosyltransferase 1A1. Front Pharmacol. 2022;13: 815235.
[99] Feng R, et al. Toxicity studies of compound spermatogenic pill: acute toxicity and subacute toxicity. J Ethnopharmacol. 2025;337: 118757.
[100] Rowland A, Miners JO, Mackenzie PI. The UDP-glucuronosyltransferases: their role in drug metabolism and detoxification. Int J Biochem Cell Biol. 2013;45(6):1121-32.
[101] Wendlocha D, et al. Selected flavonols targeting cell death pathways in cancer therapy: the latest achievements in research on apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis, and cuproptosis. Nutrients. 2024. https://doi.org/10.3390/nu16081201.
[102] Jung YY, et al. Kaempferide triggers apoptosis and paraptosis in pancreatic tumor cells by modulating the ROS production, SHP-1 expression, and the STAT3 pathway. IUBMB Life. 2024;76(9):745-59.
[103] Talib WH, et al. Natural products and altered metabolism in cancer: therapeutic targets and mechanisms of action. Int J Mol Sci. 2024. https://doi.org/10.3390/ijms25179593.
[104] Esteller M, et al. The epigenetic hallmarks of cancer. Cancer Discov. 2024;14(10):1783-809.
[105] Lee SW, Frankston CM, Kim J. Epigenome editing in cancer: advances and challenges for potential therapeutic options. Int Rev Cell Mol Biol. 2024;383:191-230.
[106] Wang L, et al. Advances in targeting tumor microenvironment for immunotherapy. Front Immunol. 2024;15:1472772.
[107] Liu Y, et al. Drug resistance and tumor immune microenvironment: an overview of current understandings (Review). Int J Oncol. 2024. https://doi.org/10.3892/ijo.2024.5684.
[108] Chhabra Y, Weeraratna AT. Fibroblasts in cancer: unity in heterogeneity. Cell. 2023;186(8):1580-609.
[109] Klemm F, Joyce JA. Microenvironmental regulation of therapeutic response in cancer. Trends Cell Biol. 2015;25(4):198-213.
[110] Xiao Y, Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther. 2021;221: 107753.
[111] Li T, Huang M, Lu J. Cancer statistics and trends in China: the potential of natural product application. Chin J Nat Med. 2024;22(8):673-5.
[112] Wang C, et al. Beneficial effects of ginkgetin on improving nonalcoholic steatohepatitis characterized by bulk and single-cell RNA sequencing analysis. Front Pharmacol. 2023;14:1267445.
[113] Wang D, et al. Cyclooxygenases and prostaglandins in tumor immunology and microenvironment of gastrointestinal cancer. Gastroenterology. 2021;161(6):1813-29.
[114] Lacher SB, et al. PGE(2) limits effector expansion of tumour-infiltrating stem-like CD8(+) T cells. Nature. 2024;629(8011):417-25.
[115] Abdolahi S, et al. Patient-derived xenograft (PDX) models, applications and challenges in cancer research. J Transl Med. 2022;20(1):206.
[116] Chen J, et al. The development and improvement of immunodeficient mice and humanized immune system mouse models. Front Immunol. 2022;13:1007579.
[117] Chen X, et al. Target identification of natural medicine with chemical proteomics approach: probe synthesis, target fishing and protein identification. Signal Transduct Target Ther. 2020;5(1):72.
[118] Ni J, et al. Vanillic acid restores homeostasis of intestinal epithelium in colitis through inhibiting CA9/STIM1-mediated ferroptosis. Pharmacol Res. 2024;202: 107128.
[119] Feng F, et al. Label-free target protein characterization for small molecule drugs: recent advances in methods and applications. J Pharm Biomed Anal. 2023;223: 115107.
[120] Wang S, et al. Labeled and label-free target identifications of natural products. J Med Chem. 2024;67(20):17980-96.
[121] Tan P, et al. Application of omics technologies in studies on antitumor effects of traditional Chinese medicine. Chin Med. 2024;19(1):123.
[122] Mullowney MW, et al. Artificial intelligence for natural product drug discovery. Nat Rev Drug Discov. 2023;22(11):895-916.
