Isoginkgetin is a biflavonoid that inhibits pancreatic lipase activity with an IC50 value of 2.9µM [1]. Isoginkgetin inhibits pre-mRNA splicing by preventing stable recruitment of the U4/U5/U6 tri-small nuclear ribonucleoprotein, resulting in accumulation of the prespliceosomal A complex [2]. Isoginkgetin has been widely used to inhibit the proliferation of tumor cells and to alter the shape of cells [3].
In vitro, Isoginkgetin (20µM) treatment for 24 hours significantly inhibited the expression of MMP-9 in HT1080 cells, increased the expression of TIMP-1, and was accompanied by a decrease in the activity of the PI3K/Akt/NF-κB pathway[4]. Treatment with 10µM Isoginkgetin for 24 hours significantly induced apoptosis in HeLa cells, resulting in the formation of aggregates around the cell nucleus, which induced endoplasmic reticulum stress and damaged the unfolded protein response [5].
In vivo, Isoginkgetin treatment via daily intraperitoneal injection at a dose of 4mg/kg for 14 days significantly inhibited the depression-like behaviors induced by lipopolysaccharide (LPS) in mice and alleviated the neurological pathological changes[6].
References:
[1] Liu P K, Weng Z M, Ge G B, et al. Biflavones from Ginkgo biloba as novel pancreatic lipase inhibitors: Inhibition potentials and mechanism[J]. International journal of biological macromolecules, 2018, 118: 2216-2223.
[2] O'Brien K, Matlin A J, Lowell A M, et al. The biflavonoid isoginkgetin is a general inhibitor of Pre-mRNA splicing[J]. Journal of Biological Chemistry, 2008, 283(48): 33147-33154.
[3] Wang Y Y, Li R H, Zhang G J, et al. The whole ginkgo resource: flowers, seeds, leaves, branches, and trees—a comprehensive review of their active ingredients, pharmacology, and applications[J]. Chemistry & Biodiversity, 2025, 22(10): e00485.
[4] Yoon S O, Shin S, Lee H J, et al. Isoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt–dependent matrix metalloproteinase-9 expression[J]. Molecular cancer therapeutics, 2006, 5(11): 2666-2675.
[5] Tsalikis J, Abdel-Nour M, Farahvash A, et al. Isoginkgetin, a natural biflavonoid proteasome inhibitor, sensitizes cancer cells to apoptosis via disruption of lysosomal homeostasis and impaired protein clearance[J]. Molecular and cellular biology, 2019, 39(10): e00489-18.
[6] Li P, Zhang F, Li Y, et al. Isoginkgetin treatment attenuated lipopolysaccharide-induced monoamine neurotransmitter deficiency and depression-like behaviors through downregulating p38/NF-κB signaling pathway and suppressing microglia-induced apoptosis[J]. Journal of psychopharmacology, 2021, 35(10): 1285-1299.