The P2Y12 receptor, activated by ADP, plays a central role in platelet activation that have proven therapeutic value. Clopidogrel is an antithrombic compound whose active metabolite is a selective, irreversible antagonist of P2Y12 receptor (IC50=100nM)[3]. Clopidogrel, administered during the last three months, significantly decreases blood glucose, collagen and fibronectin expression compared to vehicle-treated diabetic mice. Clopidogrel markedly ameliorates hyperglycemia-induced renal fibrosis[4]. The combination therapy of clopidogrel and aspirin (dual-antiplatelet therapy) has been shown to be significantly beneficial compared to aspirin monotherapy and has also shown to decrease sub-acute stent thrombosis as well as recurrent ischemic events following ACS[5].
Clopidogrel/氯吡格雷 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HepG2 cells
10 µM
24 hours
To evaluate the effect of Clopidogrel on intracellular fat deposition in HepG2 cells, results showed that Clopidogrel had no significant effect on intracellular fat deposition.
Nutrients. 2024 Mar 22;16(7):920.
Bone marrow-derived macrophages (BMDMs)
10 µM
5 days
To investigate the effect of clopidogrel on TGF-β1-induced macrophage-to-myofibroblast transition (MMT). Results showed that clopidogrel significantly inhibited P2Y12 expression, MMT, and collagen-matrix production.
Mol Ther. 2022 Sep 7;30(9):3017-3033.
mouse liver microsomes
0–50μM
20 minutes
To study the efficiency of clopidogrel metabolism to active metabolite (AM) in vitro. Results showed WT DIO liver microsomes had impaired AM generation efficiency compared to WT lean, while IL-1R−/− DIO microsomes performed similarly to WT lean.
High-fat diet-induced metabolic dysfunction-associated steatotic liver disease model
Oral
35 mg/kg/day
Once daily for 15 weeks
To evaluate the effect of Clopidogrel on a metabolic dysfunction-associated steatotic liver disease model, results showed that Clopidogrel had no significant improvement on steatosis and inflammation.
Nutrients. 2024 Mar 22;16(7):920.
C57BL/6 mice
Photothrombotic stroke model
Intraperitoneal injection
40 mg/kg
Once daily for 14 days
To investigate the impact of Clopidogrel on cognitive and motor function recovery in mice post-stroke. Results showed that Clopidogrel significantly impaired learning and memory recovery, reduced mouse survival rates and body weight, and increased vascular leakage and microglia numbers post-stroke.
Int J Mol Sci. 2023 Jul 20;24(14):11706
C57BL/6J mice and IL-1R−/− mice
Diet-induced obesity model
Oral
5 mg/kg
Single dose
To study the anti-platelet and anti-thrombotic effects of Clopidogrel in a diet-induced obesity model, it was found that wild-type DIO mice exhibited resistance to Clopidogrel, while IL-1R?/? DIO mice did not show resistance.
To investigate the therapeutic effect of clopidogrel on renal fibrosis in the UUO model. Results showed that clopidogrel significantly inhibited P2Y12 expression, TGF-β/Smad3 signaling, MMT, and renal fibrosis.
Mol Ther. 2022 Sep 7;30(9):3017-3033.
Mice
Unilateral ureteral obstruction (UUO) model
Oral
60 mg/kg/day
Once daily for 7 days (preventive study) or from day 3 to day 10 (interventional study)
To investigate the therapeutic effect of the P2Y12 inhibitor clopidogrel on renal fibrosis. Results demonstrated that clopidogrel significantly inhibited P2Y12 expression, macrophage infiltration, MMT, and renal fibrosis, and improved renal function by suppressing TGF-β/Smad3 signaling.
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