Fenofibric acid serves as an activator for PPAR, exhibiting EC50s of 22.4 µM, 1.47 µM, and 1.06 µM for PPARα, PPARγ, and PPARδ, respectively[1]. At concentrations ranging from 10 to 100 nM, Fenofibric acid progressively inhibits the COX-2 enzyme, achieving an IC50 of 48 nM[2]. At a concentration of 500 nM, Fenofibric acid leads to a reduction in the levels of AOX1 protein in HepG2 cells[3]. Fenofibric acid at 100 µM reduces phosphorylation of JNK1/2, c-Jun, and p38 MAPK, and protects against the build-up of reactive oxygen species, endoplasmic reticulum (ER) stress, and damage to the blood retinal barrier (BRB) triggered by a combination of high-glucose and hypoxic conditions in ARPE-19 cells. Additionally, at this concentration, Fenofibric acid stimulates the IGF-IR/Akt/ERK1/2-mediated survival signaling pathways in ARPE-19 cells under these stress conditions[4].
体内研究
Fenofibric acid, administered orally in doses of 1, 5, and 10 mg/kg, demonstrates anti-inflammatory effects in Wistar rats suffering from acute inflammation induced by carrageenan[2].
体外研究
Fenofibric acid serves as an activator for PPAR, exhibiting EC50s of 22.4 µM, 1.47 µM, and 1.06 µM for PPARα, PPARγ, and PPARδ, respectively[1].
At concentrations ranging from 10 to 100 nM, Fenofibric acid progressively inhibits the COX-2 enzyme, achieving an IC50 of 48 nM[2].
At a concentration of 500 nM, Fenofibric acid leads to a reduction in the levels of AOX1 protein in HepG2 cells[3].
Fenofibric acid at 100 µM reduces phosphorylation of JNK1/2, c-Jun, and p38 MAPK, and protects against the build-up of reactive oxygen species, endoplasmic reticulum (ER) stress, and damage to the blood retinal barrier (BRB) triggered by a combination of high-glucose and hypoxic conditions in ARPE-19 cells. Additionally, at this concentration, Fenofibric acid stimulates the IGF-IR/Akt/ERK1/2-mediated survival signaling pathways in ARPE-19 cells under these stress conditions[4].
Fenofibric acid/非诺贝特酸 细胞实验
Cell Line
Concentration
Treated Time
Description
References
COS-7 cells
61.0 µM
10 hours
To evaluate the effect of fenofibric acid on PPARγ-LBD-mediated gene transcription activation, results showed that fenofibric acid activated PPARγ-LBD-mediated transactivation with an EC50 of 61.0 µM.
Int J Mol Sci. 2022 Apr 25;23(9):4726.
MCF-7 breast cancer cells
20 µM
24 hours
To evaluate the effect of fenofibric acid on the antitumor effect of paclitaxel, results showed that fenofibric acid did not reduce the antitumor effect of paclitaxel
Brain Behav Immun. 2021 Mar;93:172-185.
A549 non-small cell lung cancer cells
20 µM
24 hours
To evaluate the effect of fenofibric acid on the antitumor effect of paclitaxel, results showed that fenofibric acid did not reduce the antitumor effect of paclitaxel
Brain Behav Immun. 2021 Mar;93:172-185.
AML12 cells
104.7 µM (IC50)
24 hours
To evaluate the toxicity of Mito-FFa on normal cells, results showed Mito-FFa had low toxicity on AML12 cells.
Adv Sci (Weinh). 2023 Jul;10(20):e2300286.
MDA-MB-231 tumor cells
8 µM
24 hours
To evaluate the cytotoxicity of Mito-FFa, results showed Mito-FFa had significant cytotoxicity on MDA-MB-231 cells.
Adv Sci (Weinh). 2023 Jul;10(20):e2300286.
R28 retinal precursor cells
25 µM
24 hours
To evaluate the antioxidant effect of Feno-FA on hypoxia-induced ROS generation, results showed that Feno-FA reduced ROS levels.
Invest Ophthalmol Vis Sci. 2014 May 13;55(7):4568-76.
ARPE-19 cells
100 µM
3 days
To investigate the effect of FA on high glucose and IL-1β-induced fibronectin and collagen IV overexpression. Results showed FA significantly reduced FN and Coll IV expression.
Invest Ophthalmol Vis Sci. 2011 Aug 11;52(9):6348-54.
CAOV3 ovarian cancer cells
40 µM
48 hours
To evaluate the effect of fenofibric acid on paclitaxel-induced cytotoxicity, results showed that fenofibric acid did not interfere with paclitaxel-induced cell death in CAOV3 cells.
Cancers (Basel). 2020 Dec 29;13(1):69.
SKOV-3 ovarian cancer cells
40 µM
48 hours
To evaluate the effect of fenofibric acid on paclitaxel-induced cytotoxicity, results showed that fenofibric acid did not interfere with paclitaxel-induced cell death in SKOV-3 cells.
Cancers (Basel). 2020 Dec 29;13(1):69.
4T1 tumor cells
8 µM
6 hours
To evaluate the effect of Mito-FFa on mitochondrial function, results showed Mito-FFa significantly increased mtROS generation and caused mitochondrial depolarization.
Adv Sci (Weinh). 2023 Jul;10(20):e2300286.
GL261-Red-FLuc
5, 10, 25, 50 µM
96 hours
To evaluate the cytotoxic effects of PP1 on GL261-Red-FLuc cells. Results showed that PP1 triggered extensive cell death after 96 hours.
Transl Oncol. 2019 Jul;12(7):895-907.
U-87MG
5, 10, 25, 50 µM
96 hours
To evaluate the cytotoxic effects of PP1 on U-87MG cells. Results showed that PP1 triggered extensive cell death after 96 hours.
Transl Oncol. 2019 Jul;12(7):895-907.
Fenofibric acid/非诺贝特酸 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
High-fat diet-induced retinal pigment epithelium injury model
Dietary administration
0.1%
Once daily for 1 month
Fenofibrate partially reversed the HFD-induced decrease in ERG c-wave amplitudes and suppressed oxidative injury and inflammatory response in RPE tissues
Drug Des Devel Ther. 2023 Nov 21;17:3439-3452.
C57BL/6J mice
Paclitaxel-induced peripheral neuropathy model
Dietary administration
0.2% and 0.4%
Continued for 4 weeks (before, during and after paclitaxel treatment)
To evaluate the preventive effect of fenofibrate diet on paclitaxel-induced peripheral neuropathy, results showed that fenofibrate diet partially prevented mechanical hypersensitivity, completely prevented cold hypersensitivity, and restored the decrease in sensory nerve action potential amplitude and intra-epidermal nerve fiber density.
Cancers (Basel). 2020 Dec 29;13(1):69.
Transgenic mice
Human apo A-I transgenic mice
Mixed in Mice chow for oral administration
0.5% (wt/wt)
Once daily for 7 days
To investigate the effect of fenofibrate on plasma apo A-I levels and hepatic apo A-I mRNA levels in human apo A-I transgenic mice. Results showed that treatment with 0.5% fenofibrate for 7 days increased plasma human apo A-I levels by 760% and hepatic human apo A-I mRNA levels by 97%.
J Clin Invest. 1996 Jun 1;97(11):2408-16
C57BL/6J mice
Oxygen-induced retinopathy (OIR) model
Intraperitoneal injection
10 mg/kg
Once daily from P12 to P16
To evaluate the protective effect of Feno-FA on retinal apoptosis and oxidative stress in the OIR model, results showed that Feno-FA reduced retinal apoptosis and oxidative stress.
Invest Ophthalmol Vis Sci. 2014 May 13;55(7):4568-76.
C57BL/6J mice
Oxygen-induced retinopathy (OIR) model
Intraperitoneal injection
10 mg/kg
Once daily from P12 to P17
To investigate the effect of PPARα agonist FA on retinal neovascularization and EPC mobilization in the OIR model. Results showed that FA significantly suppressed OIR-induced retinal neovascularization and EPC mobilization.
Invest Ophthalmol Vis Sci. 2014 May 20;55(6):3820-32
C57BL/6J mice
Paclitaxel-induced peripheral neuropathy model
Intraperitoneal injection
150 mg/kg
Once daily for 7 days
To evaluate the preventive and reversal effects of fenofibrate and choline fenofibrate on paclitaxel-induced peripheral neuropathy, results showed that both drugs partially or completely reversed mechanical and cold hypersensitivity and reduced neuroinflammation through PPAR-α activation
Brain Behav Immun. 2021 Mar;93:172-185.
BALB/c mice
4T1 breast tumor model
Intratumoral injection
20, 60, 200 μg/Mice
Single injection
To evaluate the antitumor effect of Mito-FFa in vivo, results showed Mito-FFa significantly inhibited tumor growth and induced CD8+ T cell-dependent immune responses.
Adv Sci (Weinh). 2023 Jul;10(20):e2300286.
Brown Norway rats
Laser-induced choroidal neovascularization (CNV) model
Intraperitoneal injection
25 mg/kg
Once daily for 2 weeks
Evaluate the effects of Feno-FA on laser-induced CNV, results showed Feno-FA significantly reduced vascular leakage and CNV volume
Invest Ophthalmol Vis Sci. 2017 Oct 1;58(12):5065-5075
C57BL/6NHsd mice
Intracranial glioblastoma model
Oral
50 mg/kg
Daily administration for 14 days
To evaluate the therapeutic effects and toxicity of PP1 in an intracranial glioblastoma model. Results showed that PP1 accumulated in tumor tissues and triggered extensive tumor cell death without significant toxicity.
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