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.
Isoginkgetin是一种双黄酮类化合物，可抑制胰脂肪酶活性，IC50值为2.9µM[1]。Isoginkgetin通过阻止U4/U5/U6三小核核糖核蛋白的稳定招募来抑制前体mRNA剪接，导致剪接前A复合物积累[2]。Isoginkgetin已被广泛用于抑制肿瘤细胞增殖并改变细胞形态[3]。
在体外，20µM的Isoginkgetin处理HT1080细胞24小时，显著抑制了MMP-9的表达，增加了TIMP-1的表达，并伴有PI3K/Akt/NF-κB通路活性的降低[4]。10µM的Isoginkgetin理HeLa细胞24小时，显著诱导了细胞凋亡，导致细胞核周围聚集物形成，诱导内质网应激并损害未折叠蛋白反应[5]。
在体内，每日腹腔注射4mg/kg剂量的Isoginkgetin，连续14天，显著抑制了脂多糖（LPS）诱导的小鼠抑郁样行为，并减轻了神经病理改变[6]。