Fraxinellone is a natural product isolated from the D. dasycarpus plant, which has been shown to exhibit neuroprotective and anti-inflammatory activities. Fraxinellone, in a dose-dependented manner, inhibited the expression of programmed cell death ligand-1 (PD-L1), which plays a pivotal role in tumorigenesis[3]. Fraxinellone attenuated the clinical and histologic features of inflammatory arthritis in CIA (collagen-induced arthritis) mice. Fraxinellone alleviated synovial inflammation and osteoclastogenesis in mice[4]. Intraperitoneal injection of fraxinellone significantly inhibited the pancreatic activation of multiple inflammasome molecules such as NACHT, LRR and PYD domains-containing protein 3 (NLRP3), PY-CARD, caspase-1, IL-18, and IL-1β during AP. In addition, fraxinellone treatment inhibited pancreatic injury, elevation in serum amylase and lipase activities, and infiltration of inflammatory cells such as neutrophils and macrophages but had no effect on pancreatic edema[5]. Moreover, fraxinellone administration caused growth arrest and certainly repressed the activity of senescence associated β-galactosidase as well as the expression of senescence-associated-genes[6].
Fraxinellone 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HT-29 cells
3, 10, 30 μM
24 hours
Inhibited TGF-β-induced fibrosis responses by inhibiting the TGF-β/Smad2/3 signaling pathway.
Acta Pharmacol Sin. 2023 Dec;44(12):2469-2478
SW480 cells
3, 10, 30 μM
24 hours
Inhibited TGF-β-induced fibrosis responses by inhibiting the TGF-β/Smad2/3 signaling pathway.
Acta Pharmacol Sin. 2023 Dec;44(12):2469-2478
Human peripheral blood mononuclear cells
40 μM
4 days
To evaluate the effect of fraxinellone on human osteoclast differentiation. Results showed that fraxinellone significantly reduced the number of TRAP-positive multinucleated cells and decreased the expression of MMP9, RANK, cathepsin K, integrin β3, and NFATc1.
Int J Mol Sci. 2018 Mar 13;19(3):829
Murine bone marrow-derived monocytes
10-40 μM
4 days
To evaluate the effect of fraxinellone on osteoclast formation. Results showed that fraxinellone inhibited the formation of TRAP-positive multinucleated cells in a dose-dependent manner and significantly reduced the expression of TRAP, cathepsin K, and MMP9.
Int J Mol Sci. 2018 Mar 13;19(3):829
CD19+ B cells
40 μM
4 days
To evaluate the effect of fraxinellone on B cell function. Results showed that fraxinellone significantly reduced the expression of AID and Blimp-1 and decreased the production of immunoglobulin G.
Int J Mol Sci. 2018 Mar 13;19(3):829
CD4+ T cells
30-50 μM
3 days
To evaluate the effect of fraxinellone on Th17 differentiation. Results showed that fraxinellone reduced the proportion of CD4+IL-17+ cells in a dose-dependent manner and significantly decreased the expression of IL-17 and RORγt.
Int J Mol Sci. 2018 Mar 13;19(3):829
SCC2095 cells
28.6 μg/ml (IC50)
48 hours
Evaluate the anti-proliferation activity of Fraxinellone against oral squamous cell carcinoma cells, showing an IC50 of 28.6 μg/ml, significantly lower than that of ZSP (>500 μg/ml)
J Ethnopharmacol. 2015 Aug 22;172:195-201
SH-SY5Y cells
≤1 μM
30 minutes
Evaluate the protective effect of Fraxinellone against glutamate toxicity, results showed no significant protection at ≤1 μM
ACS Chem Neurosci. 2024 Jul 17;15(14):2612-2622
PC12 cells
≤1 μM
30 minutes
Evaluate the protective effect of Fraxinellone against glutamate toxicity, results showed no significant protection at ≤1 μM
ACS Chem Neurosci. 2024 Jul 17;15(14):2612-2622
human hypertrophic scar-derived fibroblasts (HSFs)
100 µM, 200 µM, 300 µM
48 hours
To evaluate the effect of FRA on the proliferation and migration capacity of HSFs. Results showed that FRA significantly suppressed the proliferation and migration of HSFs.
Biol Direct. 2025 Feb 4;20(1):17
human osteosarcoma cell line MG63
0-320μM
0-48 hours
FRA inhibited the proliferation and migration of MG63 cells in a dose-dependent manner
Front Pharmacol. 2021 Apr 19;12:653212
human osteosarcoma cell line HOS
0-320μM
0-48 hours
FRA inhibited the proliferation and migration of HOS cells in a dose-dependent manner
Front Pharmacol. 2021 Apr 19;12:653212
Fraxinellone 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
Bile duct ligation (BDL)-induced liver fibrosis
Gavage
10, 20, 40 mg/kg
Once daily for 4 weeks
Fraxinellone significantly ameliorated BDL-induced liver fibrosis, including reduced collagen deposition, serum hyaluronic acid, laminin, and type III procollagen levels, as well as liver hydroxyproline content.
Nat Commun. 2016 Nov 17;7:13498
C57BL/6 mice
DSS-induced intestinal fibrosis model
Intragastric administration
7.5, 15, 30 mg/kg/d
Once daily for 45 days
Dose-dependently alleviated DSS-induced intestinal impairments and reduced the production of intestinal fibrosis biomarkers.
Acta Pharmacol Sin. 2023 Dec;44(12):2469-2478
DBA/1J mice
Collagen-induced arthritis (CIA) model
Intraperitoneal injection
7.5 mg/kg
Three times per week for eight weeks
To evaluate the therapeutic effect of fraxinellone on inflammatory arthritis. Results showed that fraxinellone significantly attenuated the clinical and histologic features of arthritis, reduced serum IgG levels, and inhibited the production of TNF-α and IFN-γ.
Int J Mol Sci. 2018 Mar 13;19(3):829
New Zealand white rabbits
Rabbit ear scar model
Subcutaneous injection
100 µM, 300 µM
Every other day for 14 days
To validate the therapeutic efficacy of FRA on scar formation in vivo. Results showed that FRA significantly attenuated scar formation and improved collagen fiber arrangement.
Biol Direct. 2025 Feb 4;20(1):17
Nude mice
Osteosarcoma xenograft model
Gavage
50 mg/kg and 100 mg/kg
Once daily for 21 days
FRA treatment inhibited the growth of osteosarcoma, and the pro-apoptotic and autophagy effects of FRA were also proved in vivo
Front Pharmacol. 2021 Apr 19;12:653212
Zebrafish
Zebrafish larvae
Culture medium exposure
10–30 μM
48 hours
To evaluate the hepatotoxicity of FRA and its mechanism, the results showed that FRA induces apoptosis by increasing the level of ROS and activating the JNK/P53 pathway, and induces cholestasis by down-regulating bile acid transporters P-gp, Bsep, and Ntcp.
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