Triptonide, a natural product isolated and purified from the herb of Tripterygium wilfordii Hook.f. with antileukemic, antitumor, anti-inflammatory activities, is effective in the treatment of autoimmune diseases. Triptonide can effectively inhibit canonical Wnt/β-catenin signaling by targeting the downstream C-terminal transcription domain of β-catenin or a nuclear component associated with β-catenin. In addition, triptonide treatment robustly rescued the zebrafish "eyeless" phenotype induced by GSK-3β antagonist 6-bromoindirubin-30-oxime (BIO) for Wnt signaling activation during embryonic gastrulation[3]. Triptonide effectively suppressed TNBC (Triple-negative breast cancer) cell tumorigenesis, vasculogenic mimicry, and strongly inhibited the metastasis of TNBC via degradation of Twist1 and Notch1 oncoproteins, downregulation of metastatic and angiogenic gene expression, and reduction of NF-κB signaling pathway[4]. Single daily oral doses of triptonide induces deformed sperm with minimal or no forward motility (close to 100% penetrance) and consequently male infertility in 3-4 and 5-6 weeks in mice and cynomolgus monkeys, respectively[5].
Triptonide/雷公藤内酯酮 细胞实验
Cell Line
Concentration
Treated Time
Description
References
THP-1 cells
1, 5, 10, 20 ng/ml
1, 6, 12, 18 hours
To investigate the effect of Triptonide on IL-37 mRNA expression. Results showed that 20 ng/ml of Triptonide upregulated IL-37 mRNA expression approximately 3.2-fold after 12 hours of incubation.
Cell Mol Immunol. 2015 Jul;12(4):515-8
Rat intestine
3–9 μg/mL
10 minutes
Evaluate the absorption characteristics of Triptonide in rat intestine, showing that its absorption extent and rate were independent of concentration.
Chin Med. 2018 Jan 8;13:1
THP-1 cells
20 ng/ml
16 hours
To investigate the effect of Triptonide on IL-37 protein expression. Results showed that 20 ng/ml of Triptonide upregulated IL-37 protein expression approximately 3.4-fold after 16 hours of incubation.
Cell Mol Immunol. 2015 Jul;12(4):515-8
ARPE-19 cells
10-100 nM
24 hours
To evaluate the effect of Triptonide on cell viability, results showed no significant impact on cell viability at concentrations below 100 nM.
Int J Mol Med. 2024 Sep;54(3):76
Müller cells (MIO-M1)
10-100 nM
24 hours
To evaluate the effect of Triptonide on cell viability, results showed no significant impact on cell viability at concentrations below 100 nM.
Int J Mol Med. 2024 Sep;54(3):76
Human retinal capillary endothelial cells (HRCECs)
10-100 nM
24 hours
To evaluate the effect of Triptonide on cell viability, results showed no significant impact on cell viability at concentrations below 100 nM.
Int J Mol Med. 2024 Sep;54(3):76
Human umbilical vein endothelial cells (HUVECs)
10-100 nM
24 hours
To evaluate the effect of Triptonide on cell viability, results showed no significant impact on cell viability at concentrations below 100 nM.
Int J Mol Med. 2024 Sep;54(3):76
RKO cells
5 nM
24 hours
Did not block BIO-induced β-catenin nuclear translocation
Sci Rep. 2016 Sep 6;6:32779
HEK293 cells
5 nM
24 hours
Did not affect Wnt3a-CM-induced β-catenin levels
Sci Rep. 2016 Sep 6;6:32779
SKBR3
0.2 µM
24, 48, 72 hours
Inhibits cell growth
Sci Rep. 2021 Jan 28;11(1):2408
MCF7
0.2 µM
24, 48, 72 hours
Inhibits cell growth
Sci Rep. 2021 Jan 28;11(1):2408
MDA-MB-231
0.2 µM
24, 48, 72 hours
Inhibits TNBC cell growth
Sci Rep. 2021 Jan 28;11(1):2408
BT549
0.2 µM
24, 48, 72 hours
Inhibits TNBC cell growth
Sci Rep. 2021 Jan 28;11(1):2408
HCC1806
0.2 µM
24, 48, 72 hours
Inhibits TNBC cell growth and induces apoptosis
Sci Rep. 2021 Jan 28;11(1):2408
U-2OS cells
5, 10, 25, 50, 100, 250 and 1000 nM
48 hours
TN inhibited the proliferation of U-2OS cells in a dose-dependent manner with an IC50 of 97.2 nM
Cancer Manag Res. 2020 Jul 17;12:5919-5929
MG63 cells
5, 10, 25, 50, 100, 250 and 1000 nM
48 hours
TN inhibited the proliferation of MG63 cells in a dose-dependent manner with an IC50 of 108.6 nM
Cancer Manag Res. 2020 Jul 17;12:5919-5929
BT-549
0–320 nM
70 hours
Inhibited TNBC cell proliferation with an IC50 of 12.1 nM.
Breast Cancer Res. 2021 Dec 18;23(1):116
SW480 cells
16.8 nM (IC50)
72 hours
Induced apoptosis
Sci Rep. 2016 Sep 6;6:32779
MDA-MB-468
0–320 nM
70 hours
Inhibited TNBC cell proliferation with an IC50 of 14.4 nM.
Breast Cancer Res. 2021 Dec 18;23(1):116
MDA-MB-231
0–320 nM
70 hours
Inhibited TNBC cell proliferation with an IC50 of 15.6 nM.
Breast Cancer Res. 2021 Dec 18;23(1):116
Pancreatic cancer cell Panc1
8 nM
72 hours
Inhibited the LXR-SREBF1-PNKP signaling pathway, increased DNA strand breaks, and induced apoptosis
Cell Death Differ. 2020 Aug;27(8):2433-2450
Pancreatic cancer cell Patu8988
8 nM
72 hours
Inhibited the LXR-SREBF1-PNKP signaling pathway, increased DNA strand breaks, and induced apoptosis
Cell Death Differ. 2020 Aug;27(8):2433-2450
ST2 cells
10 nM
72 hours
Triptonide blocks the Wnt signaling pathway by binding to the C-terminal transactivation domain of β-catenin, thereby inhibiting C91-induced osteoblast differentiation in ST2 cells.
Front Endocrinol (Lausanne). 2022 Jul 18;13:926622
Triptonide/雷公藤内酯酮 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Cynomolgus monkeys
Adult male C57BL/6J and CD-1 mice, adult male cynomolgus monkeys
Oral
0.1 mg/kg
Mice: once daily for 3-4 weeks; Monkeys: once daily for 5-6 weeks
To evaluate the efficacy and safety of Triptonide as a male contraceptive. Results showed that Triptonide induced sperm deformation and loss of motility, leading to male infertility within 3-4 weeks (mice) and 5-6 weeks (monkeys), with no discernable systematic toxic side effects.
Nat Commun. 2021 Feb 23;12(1):1253
Mice
Adult male C57BL/6J and CD-1 mice, adult male cynomolgus monkeys
Oral
0.8 mg/kg
Mice: once daily for 3-4 weeks; Monkeys: once daily for 5-6 weeks
To evaluate the efficacy and safety of Triptonide as a male contraceptive. Results showed that Triptonide induced sperm deformation and loss of motility, leading to male infertility within 3-4 weeks (mice) and 5-6 weeks (monkeys), with no discernable systematic toxic side effects.
Nat Commun. 2021 Feb 23;12(1):1253
C57BL/6 male mice
Light-induced and N-Methyl-D-aspartic acid (NMDA)-induced retinal injury models
Intravitreal injection
2 µl of Tn (1 mg/ml)
Single injection, lasting 7 days
To evaluate the protective effect of Triptonide on light-induced and NMDA-induced retinal injury, results showed that Triptonide pretreatment significantly improved retinal function and structure and inhibited choroidal neovascularization.
Int J Mol Med. 2024 Sep;54(3):76
NOD-SCID female mice
TNBC MDA-MB-231 xenograft model
Intraperitoneal injection
3 mg/kg
Once daily for 95 days
Suppressed TNBC tumor growth and lung metastasis with a tumor inhibitory rate of 98%.
Breast Cancer Res. 2021 Dec 18;23(1):116
Sprague-Dawley rats
Single-pass intestinal perfusion model
Intestinal perfusion
3–9 μg/mL
Single perfusion, lasting 80 minutes
Evaluate the absorption characteristics of Triptonide in rat intestine, showing that its absorption extent and rate were independent of concentration.
Chin Med. 2018 Jan 8;13:1
Nude mice
MDA-MB-231 xenograft model
Oral gavage
5 mg/kg
Once daily for 17 days
Inhibits xenograft tumor growth
Sci Rep. 2021 Jan 28;11(1):2408
Nude mice
Pancreatic cancer Patu8988 xenograft model
Intraperitoneal injection
5 mg/kg/d
Once daily for 73 days
Inhibited tumor growth, with complete elimination of tumors in five out of eight xenograft mice and an overall inhibition rate of 99.6%
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