Isorhapotogenin is a natural product isolated and purified from the herbs of Gnetum montanum Markgr. Isorhapontigenin (Isor) is a new derivative of stilbene and responsible for a wide range of biological processes. Isor effectively relieved Dox-induced cardiomyocytes apoptosis in a dose-dependent manner in vitro. Administration with Isor (30 mg/kg/day, intraperitoneally, 3 weeks) significantly protected against Dox-induced cardiotoxicity in mice[3]. ISO effectively ameliorated lipopolysaccharide-induced ALI by reducing inflammation and oxidative stress, primarily through activation of Nrf2 (Nuclear factor erythroid-2 related factor 2) signaling[4]. ISO protected against oxidative damage induced by brain I/R (cerebral ischemia/reperfusion), and its neuroprotective mechanism may be related to the PKCε/Nrf2/HO-1 pathway[5]. ISO successfully induced breast cancer cell death and cell growth arrest, suggesting this phytochemical is a better alternative for breast cancer treatment[6].
Isorhapontigenin/异丹叶大黄素 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Patient-derived glioblastoma spheres JX6
20 μM
24 hours
To evaluate the inhibitory effect of ISO on anchorage-independent growth in JX6 cells. Results showed that ISO significantly inhibited growth in JX6 cells.
Neuro Oncol. 2016 Jun;18(6):830-9
Patient-derived glioblastoma spheres D456
20 μM
24 hours
To evaluate the inhibitory effect of ISO on anchorage-independent growth and induction of G0-G1 cell cycle arrest in D456 cells. Results showed that ISO significantly inhibited growth and induced G0-G1 arrest in D456 cells.
Neuro Oncol. 2016 Jun;18(6):830-9
human cervical cancer HeLa cells
2.5-10 μM
24 hours
Induced autophagy and inhibited anchorage-independent growth
Autophagy. 2016 Aug 2;12(8):1229-39
human bladder cancer T24T cells
2.5-10 μM
24 hours
Induced autophagy and inhibited anchorage-independent growth
Autophagy. 2016 Aug 2;12(8):1229-39
human bladder cancer UMUC3 cells
2.5-10 μM
24 hours
Induced autophagy and inhibited anchorage-independent growth
Autophagy. 2016 Aug 2;12(8):1229-39
Neonatal rat cardiomyocytes (NRCMs)
1-40 μmol/L
12 hours
Isor effectively alleviated Dox-induced cardiomyocyte apoptosis in a dose-dependent manner.
Acta Pharm Sin B. 2021 Mar;11(3):680-693
Primary human airway epithelial cells
1-100 μM
1 hour
To evaluate the inhibitory effects of isorhapontigenin on IL-6 and CXCL8 release, results showed that isorhapontigenin concentration-dependently inhibited IL-6 and CXCL8 release, with IC50 values at least twofold lower than those of resveratrol.
Br J Pharmacol. 2017 Jul;174(13):2043-2059
A549 cells
1-100 μM
1 hour
To evaluate the inhibitory effects of isorhapontigenin on IL-6 and CXCL8 release, results showed that isorhapontigenin concentration-dependently inhibited IL-6 and CXCL8 release, with IC50 values at least twofold lower than those of resveratrol.
Br J Pharmacol. 2017 Jul;174(13):2043-2059
UMUC3 cells
10 μM
24 hours
ISO treatment upregulated RAC1 protein translation and MKK7/JNK phosphorylation/activation, thereby promoting autophagic responses and inhibiting bladder cancer cell invasion.
Cell Death Dis. 2022 Aug 31;13(8):753
T24T cells
20 μM
24 hours
ISO inhibits invasion of bladder cancer cells by upregulating METTL14
Cancer Lett. 2021 Nov 1;520:400-408
U5637 cells
20 μM
24 hours
ISO inhibits invasion of bladder cancer cells by upregulating METTL14
Cancer Lett. 2021 Nov 1;520:400-408
UMUC3 cells
5 μM
12 hours
ISO treatment increased miR-137 expression and specifically inhibited the invasion ability of UMUC3 cells
Mol Ther Nucleic Acids. 2018 Sep 7;12:337-349
T24T cells
10 μM
12 hours
ISO treatment increased miR-137 expression and specifically inhibited the invasion ability of T24T cells
Mol Ther Nucleic Acids. 2018 Sep 7;12:337-349
SH-SY5Y cells
1, 5, 10, and 20 μM
24 hours
To evaluate the neuroprotective effects of isorhapontigenin against Aβ peptide (25-35)-induced cell death. Results showed that pre-treatment with isorhapontigenin for 24 hours significantly elevated cell viabilities and produced significant differences as compared to the control (p < 0.05*, 0.01**, 0.001***).
Antioxidants (Basel). 2023 Jun 29;12(7):1362
T24T bladder cancer cells
20 μM
12 hours
ISO significantly inhibited sphere formation and invasivity of T24T cells by down-regulating CD44 protein expression
Cell Mol Life Sci. 2020 Jan;77(2):351-363
Cl41 cells
5 μM
24 hours
To study the effect of ISO on Cyclin D1 expression in normal Cl41 cells, results showed that ISO had minimal effect on Cyclin D1 expression.
Mol Cancer Ther. 2013 Aug;12(8):1492-503
RT4 cells
5 μM
24 hours
To study the effect of ISO on Cyclin D1 expression in RT4 cells, results showed that ISO slightly inhibited Cyclin D1 expression.
Mol Cancer Ther. 2013 Aug;12(8):1492-503
RT112 cells
5 μM
24 hours
To study the effect of ISO on Cyclin D1 expression in RT112 cells, results showed that ISO significantly inhibited Cyclin D1 expression.
Mol Cancer Ther. 2013 Aug;12(8):1492-503
UMUC3 cells
5-60 μM
48 hours
To evaluate the inhibitory effect of ISO on the proliferation of human bladder cancer cells, results showed that ISO significantly reduced the viability of UMUC3 and RT4 cells in a concentration-dependent manner.
Mol Cancer Ther. 2013 Aug;12(8):1492-503
Isorhapontigenin/异丹叶大黄素 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
Xenograft model with human bladder cancer T24T cells
150 mg/kg/d
Once daily, duration
Markedly inhibited xenograft tumor growth
Autophagy. 2016 Aug 2;12(8):1229-39
C57BL/6 mice
Dox-induced cardiotoxicity model
Intraperitoneal injection
30 mg/kg/day
Once daily for 3 weeks
Isor significantly protected mice against Dox-induced cardiotoxicity and improved cardiac function.
Acta Pharm Sin B. 2021 Mar;11(3):680-693
Sprague-Dawley rats
Intravenous injection and oral
30 μmol/kg (i.v.) and 600 μmol/kg (p.o.)
Single dose
To evaluate the pharmacokinetic profile of isorhapontigenin, results showed that its oral bioavailability was approximately 50% higher than resveratrol.
Br J Pharmacol. 2017 Jul;174(13):2043-2059
Mice
BBN-induced muscle-invasive bladder cancer model
150 mg/kg/day
Daily administration
ISO significantly inhibited BBN-induced muscle-invasive bladder cancer formation in mice, with an inhibition rate of over 90%.
Cell Death Dis. 2022 Aug 31;13(8):753
Wistar male mice
Gastric gavage
150 mg/kg
Single dose, observation time points included 0.033h, 0.083h, 0.17h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h and 4h
To study the pharmacokinetics of ISO in mice, results showed that the maximum observed concentration (Cmax) of ISO in mouse serum was 12.35 μg/ml (47.9 μM), reached at 0.17 h (10 min).
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