Diosbulbin B, a natural product isolated and purified from the roots of Dioscorea bulbifera, has potential anti-tumor effects which may be related to influencing the immune system for the first time. Liver hydroxyproline content, hepatic collagen deposition and immune cells infiltration were increased in mice treated with DB (50 mg/kg) for 2 months. Serum amounts of hyaluronic acid and laminin were increased in mice treated with DB for 1 or 2 months. DB (50 mg/kg) induced hepatic stellate cells (HSCs) activation when mice were treated with DB for 2 months. Liver mRNA expression of Col1a1, Col1a2, Col3a1, fibronectin (Fn1), vimentin (Vim) and fibroblast-specific protein 1 (FSP1) were all increased in DB-treated mice[3]. DB (Diosbulbin B) induced hepatotoxicity by inducing G2/M cell cycle arrest in hepatocytes via miR-186-3p or miR-378a-5p-mediated the reduced CDK1 (cyclin-dependent kinase 1) expression[4]. Specifically, high-dose DB (50μM) significantly inhibited cell proliferation and promoted cell apoptosis, while low dose DB (12.5μM) had little effects on cell viability. Besides, high-dose DB (50μM) significantly decreased CircRNA CDR1as levels in gastric cancer cells instead of hepatocytes. Notably, knock-down of CircRNA CDR1as triggered low-dose DB (12.5μM) induced GC cell death, but had little effects on hepatocytes proliferation and apoptosis[5].
Diosbulbin B/黄独素B 细胞实验
Cell Line
Concentration
Treated Time
Description
References
BGC823/CDDP cells
12.5 μM
0 h, 24 h, 48 h, 72 h
Low-dose DB significantly induced apoptotic cell death in cisplatin-treated CR-GC cells and triggered NLRP3-mediated pyroptosis.
Cell Biosci. 2021 Feb 12;11(1):38
SGC7901/CDDP cells
12.5 μM
0 h, 24 h, 48 h, 72 h
Low-dose DB significantly induced apoptotic cell death in cisplatin-treated CR-GC cells and triggered NLRP3-mediated pyroptosis.
Cell Biosci. 2021 Feb 12;11(1):38
mouse liver microsomes
200 μM
30 minutes
To study the metabolic activation of Diosbulbin B and its covalent binding to proteins
Toxins (Basel). 2017 Aug 14;9(8):249
HGC-27 cells
0, 3.125, 6.25, 12.5, 25, 50, or 100 µM
48 hours
To detect the IC50 of Diosbulbin B in HGC-27 cells, results showed that circHECTD1 deficiency enhanced the sensitivity to Diosbulbin B.
Cancer Cell Int. 2021 May 17;21(1):264
AGS cells
0, 3.125, 6.25, 12.5, 25, 50, or 100 µM
48 hours
To detect the IC50 of Diosbulbin B in AGS cells, results showed that circHECTD1 deficiency enhanced the sensitivity to Diosbulbin B.
Cancer Cell Int. 2021 May 17;21(1):264
L-02 hepatocytes
50, 100, 200 µM
48 hours
To investigate the toxicity of DB on L-02 hepatocytes and its mechanism. Results showed that DB significantly decreased cell viability, induced concentration-dependent apoptosis and autophagy, increased the activities of caspase-3, caspase-9, ALT, and AST, and caused excessive leakage of LDH.
Front Pharmacol. 2019 Jun 19;10:676
Primary rat hepatocytes
100 μM
0 h, 6 h, 12 h, 18 h and 24 h
To evaluate the effects of high-dose DB on hepatocyte proliferation and apoptosis, results showed that high-dose DB inhibited proliferation and induced apoptosis, which were reversed by ASP co-treatment.
Bioengineered. 2021 Dec;12(1):3516-3524
Diosbulbin B/黄独素B 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c mice
Xenograft tumor-bearing model
12.5 μM
30 days
Low-dose DB enhanced the inhibitory effects of cisplatin on CR-GC cells, reducing tumor volume and weight.
Cell Biosci. 2021 Feb 12;11(1):38
Mice
Hepatotoxicity model
Intraperitoneal injection
75, 150, 200 mg/kg
Single dose, liver harvested 12 hours post administration
To study the hepatotoxicity of Diosbulbin B in vivo and its covalent binding to proteins
Toxins (Basel). 2017 Aug 14;9(8):249
ICR male mice
Pulmonary toxicity model
Oral gavage
10, 30, 60 mg/kg
4 consecutive weeks
To study the toxic effects of Diosbulbin B on mouse lungs and its mechanism. Results showed that DIOB induced lung toxicity by increasing plasma levels of long-chain free fatty acids and inflammation-related endogenous metabolites, and by inhibiting fatty acid β-oxidation, partial glycolysis, and the TCA cycle.
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