Isoginkgetin is a MMP-9 inhibitor isolated and purified from the leaves of Ginkgo biloba L., also a Pre-mRNA Splicing inhibitor with IC50 of 30 μM. Isoginkgetin inhibits HT1080 tumor cell invasion substantially. Isoginkgetin was also quite effective in inhibiting the activities of Akt and MMP-9 in MDA-MB-231 breast carcinomas and B16F10 melanoma[3]. Isoginkgetin disturbs protein homeostasis, leading to an excess of protein cargo that places a burden on the lysosomes/autophagic machinery, eventually leading to cancer cell death[4]. In vitro, isoginkgetin markedly suppressed the production of IL-1β, IL-6, tumor necrosis factor-alpha, cyclooxygenase-2, inducible NO, and ROS, which are released from LPS-stimulated BV2 cells. Moreover, CM (conditioned medium) from isoginkgetin-treated BV2 cells significantly alleviated SH-SY5Y cell apoptosis and restored cell viability compared to LPS-treated group through the inhibition of p38/NF-κB signaling pathway[5]. Blocking IL-32 alternative splicing by Isoginkgetin resulted in predominant expression of IL-32γ splice variants and cell death in TC (thyroid cancer) cell lines[6]. At 10 uM, isoginkgetin showed the suppressive activity against lymphocyte proliferation induced by Con A or LPS[7].
Isoginkgetin/异银杏素 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Huh7
20 µM
14 days
ISO significantly inhibited colony formation in Huh7 cells.
Autophagy. 2023 Apr;19(4):1221-1238.
U87MG glioblastoma cells
15 and 25 µM
1, 2, and 3 days
Growth curves and MTT toxicity assays showed time and dose-dependent growth inhibition of U87MG after treatment with Iso (15/25 µM) for 1, 2, and 3 days.
Molecules. 2022 Nov 29;27(23):8335.
HepG2
20 µM
24 hours
ISO induced autophagosome formation in HepG2 cells, as evidenced by increased LC3-II expression.
Autophagy. 2023 Apr;19(4):1221-1238.
U87MG glioblastoma cells
15 and 25 µM
24 hours
The colony formation test showed that iso treatment for 24 h reduced colony formation.
Molecules. 2022 Nov 29;27(23):8335.
Vero cells
22.81 µM (IC50)
24 hours
To evaluate the antiviral activity of Isoginkgetin against SARS-CoV-2, results showed an IC50 of 22.81 μM, significantly inhibiting viral replication
J Mol Liq. 2022 May 1;353:118775.
BV2 cells
0.1 µM and 0.5 µM
24 hours
To evaluate the effect of Isoginkgetin on the release of inflammatory mediators in LPS-activated BV2 cells. Results showed that Isoginkgetin significantly inhibited mRNA expression of IL-1β, IL-6, and COX-2, and reduced NO and ROS production.
J Psychopharmacol. 2021 Oct;35(10):1285-1299.
U87MG glioblastoma cells
15 µM
24, 48, and 72 hours
The FACS analysis showed that treatment with Iso 15 µM determines a blockage of the cell cycle in the S1 phase.
Molecules. 2022 Nov 29;27(23):8335.
Human liver microsomes
0.982 ± 0.006 µM (IC50)
30 minutes
To evaluate the inhibitory effect of Isoginkgetin on CYP3A4, the results showed an IC50 of 0.982 ± 0.006 μM, indicating significant inhibition of CYP3A4.
Front Pharmacol. 2022 Feb 28;13:856784.
H9C2 cardiomyocytes
10 µM
48 hours
To evaluate the protective effect of IGK on PA-induced cardiomyocyte injury. Results showed that IGK significantly alleviated PA-induced cardiomyocyte hypertrophy and oxidative stress, and enhanced mitochondrial respiratory capacity.
Redox Biol. 2022 Nov;57:102485.
Neonatal rat cardiomyocytes (NRCMs)
10 µM
48 hours
To evaluate the protective effect of IGK on PA-induced cardiomyocyte injury. Results showed that IGK significantly alleviated PA-induced cardiomyocyte hypertrophy and oxidative stress, and enhanced mitochondrial respiratory capacity.
To identify specific stages of mRNA synthesis influenced by IsoG, found that IsoG inhibits transcription elongation
Nat Chem Biol. 2017 May;13(5):501-507.
HeLa S3 cells
30 µM
6 hours
To investigate the effect of Isoginkgetin on the transcriptome of HeLa S3 cells, revealing widespread accumulation of RNA polymerase II at the 5' ends of genes, indicating its role as an RNA polymerase II elongation inhibitor.
Genome Biol. 2021 Feb 2;22(1):55.
Recombinant CES2
0.07 µM
Evaluate the inhibitory potential of Isoginkgetin on CES2-catalyzed 4-MUA hydrolysis, showing potent inhibition
Front Pharmacol. 2021 May 18;12:655659.
Human intestinal microsomes (HIMs)
0.94 µM
Evaluate the inhibitory potential of Isoginkgetin on CES2-catalyzed irinotecan hydrolysis, showing potent inhibition
Front Pharmacol. 2021 May 18;12:655659.
Human liver microsomes (HLMs)
32.24 nM
Evaluate the inhibitory potential of Isoginkgetin on CES2-catalyzed FD hydrolysis, showing potent inhibition
Front Pharmacol. 2021 May 18;12:655659.
Isoginkgetin/异银杏素 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
High-fat diet-induced obesity model
Tail vein injection
0.5 mg/kg
Once a week for 4 weeks
To evaluate the protective effect of IGK on obesity-induced cardiomyopathy. Results showed that IGK significantly improved diastolic function, alleviated cardiac hypertrophy and fibrosis, activated Nrf2/ARE signaling pathway, and improved mitochondrial function in obese mice.
Redox Biol. 2022 Nov;57:102485.
BALB/c nude mice
HepG2 xenograft model
Intraperitoneal injection
25 mg/kg and 50 mg/kg
Once daily for 14 days
ISO significantly reduced the volume and weight of HepG2 xenograft tumors.
Autophagy. 2023 Apr;19(4):1221-1238.
Kunming mice
LPS-induced depression model
Intraperitoneal injection
4 mg/kg
Once daily for 14 days
To evaluate the effect of Isoginkgetin on LPS-induced depression-like behaviors. Results showed that Isoginkgetin significantly reversed LPS-induced depression-like behaviors, reduced serum IL-1β levels, and restored hippocampal neurotransmitter levels.
J Psychopharmacol. 2021 Oct;35(10):1285-1299.
SD rats
Needle puncture-induced intervertebral disc degeneration model
Local injection
60 μg/mL
Weekly for 8 weeks
Evaluate the therapeutic effect of IGK@SeNP on intervertebral disc degeneration in vivo, showing significant preservation of disc height and water content
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