PPAR (peroxisome proliferator-activated receptors) are ligand-activated transcription factors of nuclear hormone receptor superfamily comprising of PPARα, PPARγ, and PPARβ/δ[3]. Gemfibrozil is a PPARα and PPARγ agonist (EC50s = 193.3 and 147.8 µM, respectively)[4]. In vivo, gemfibrozil (50 mg/kg, p.o.) reduces serum total cholesterol, triglyceride, and LDL levels in a rat model of high-cholesterol diet-induced hyperlipidemia[5]. Gemfibrozil (100 mg/kg per day) reduces atherosclerotic plaque area, superoxide production, and expression of the genes encoding the NF-κB subunit p65 and chemokine (C-C) motif ligand 2 (CCL2) in ApoE-/- mice. Formulations containing gemfibrozil have been used in the treatment of high cholesterol[6].
Gemfibrozil/吉非罗齐 细胞实验
Cell Line
Concentration
Treated Time
Description
References
mouse primary astrocytes
10 μM
24 hours
GFB-RA treatment enhanced the uptake of Aβ in astrocytes via LDLR-mediated endocytosis.
Sci Signal. 2021 Oct 26;14(706):eabg4747
hippocampal neurons
25 μM
24 hours
Gemfibrozil significantly induced ADAM10 expression and reduced Aβ production
Proc Natl Acad Sci U S A. 2015 Jul 7;112(27):8445-50
Beas2b cells
10 μM
12 hours
Gemfibrozil significantly reduces CSE-induced autophagy impairment and aggresome formation by inducing TFEB and controlling ROS activity.
Antioxid Redox Signal. 2017 Jul 20;27(3):150-167
human microglia (HM) cells
different concentrations
24 hours
Gemfibrozil increased the protein level of LC3B-II:LC3B-I and decreased the protein level of SQSTM1 in a dose-dependent manner, indicating autophagy induction.
Autophagy. 2020 Jan;16(1):52-69
Acinetobacter baylyi ADP1
0.005, 0.05, 0.5, 5, 50 mg/L
6 hours
To investigate the effect of gemfibrozil on the transformation frequency of Acinetobacter baylyi ADP1. Results showed that gemfibrozil significantly increased the transformation frequency of ARGs at concentrations as low as 0.005 mg/L, reaching up to 5.97 × 10−6 per total bacteria.
ISME J. 2020 Aug;14(8):2179-2196
COS7 cells
100 μM
To evaluate the response of α1C517Yβ1 sGC variant to gemfibrozil, results showed that α1C517Yβ1 sGC had a stronger response to gemfibrozil compared to wild-type sGC
Biochem Pharmacol. 2021 Apr;186:114459
U251-APP cells
200 μM
24 hours
Gemfibrozil treatment increased LC3B-II:LC3B-I protein levels and decreased SQSTM1 protein levels, indicating autophagy induction.
Autophagy. 2020 Jan;16(1):52-69
Gemfibrozil/吉非罗齐 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
5XFAD mouse model
Oral
8 mg/kg/day GFB + 150 IU/day RA
Once daily for 60 days
Oral GFB-RA stimulated lysosomal biogenesis, reduced plaque load and improved spatial learning and memory in the 5XFAD mouse model of AD via astroglial PPAR α.
Sci Signal. 2021 Oct 26;14(706):eabg4747
Mice
APP-PSEN1 ΔE9 mouse model
Oral administration in drinking water
50 μg/mL
For 2 months
Gemfibrozil improved spatial learning and memory deficits, reduced anxiety symptoms, and decreased soluble and insoluble Aβ levels in the hippocampus and cortex tissues of APP-PSEN1 ΔE9 mice.
Autophagy. 2020 Jan;16(1):52-69
Wistar rats
Male Wistar rats
Transdermal administration
46 mg/kg (transdermal administration)
24 hours
To investigate the pharmacokinetic properties of Gemfibrozil in transdermal drug delivery system
Acta Pharm Sin B. 2020 May;10(5):928-945
C57BL/6 mice
Subchronic cigarette smoke-induced COPD-emphysema model
Intraperitoneal injection
40 mg/kg body weight
Alternate days for 10 days
Gemfibrozil significantly reduces CS-induced autophagy impairment, inflammation (IL-6 levels), apoptosis (caspase-3/7 activity), and emphysema (alveolar airspace enlargement) by inducing TFEB.
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