ArticleOxidative medicine and cellular longevity2016
Synergistic Effects of Cilostazol and Probucol on ER Stress-Induced Hepatic Steatosis via Heme Oxygenase-1-Dependent Activation of Mitochondrial Biogenesis.
Article in Oxidative medicine and cellular longevity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Repurposing of Antiplatelet Agent: Cilostazol for the Treatment of Alcohol-Related Liver Disease.Gut and liver · 2025Review
- Theoretical Investigations on Free Energy of Binding Cilostazol with Different Cyclodextrins as Complex for Selective PDE3 Inhibition.Molecules (Basel, Switzerland) · 2024Article
- Role and mechanism of specialized pro-resolving mediators in obesity-associated insulin resistance.Lipids in health and disease · 2024Review
- Mechanism of Action and Related Natural Regulators of Nrf2 in Nonalcoholic Fatty Liver Disease.Current drug delivery · 2024Review
- Azorean Black Tea (Molecules (Basel, Switzerland) · 2023Article
- Protective effect of cilostazol and verapamil against thioacetamide-induced hepatotoxicity in rats may involve Nrf2/GSK-3β/NF-κB signaling pathway.Toxicology research · 2022Article
- Could cilostazol be beneficial in COVID-19 treatment? Thinking about phosphodiesterase-3 as a therapeutic target.International immunopharmacology · 2021Review
- Neohesperidin enhances PGC-1α-mediated mitochondrial biogenesis and alleviates hepatic steatosis in high fat diet fed mice.Nutrition & diabetes · 2020Article
- Theaflavins Improve Insulin Sensitivity through Regulating Mitochondrial Biosynthesis in Palmitic Acid-Induced HepG2 Cells.Molecules (Basel, Switzerland) · 2018Article
- Mitochondrial role in the neonatal predisposition to developing nonalcoholic fatty liver disease.The Journal of clinical investigation · 2018Review
- Mitochondrial-Based Therapeutics for the Treatment of Spinal Cord Injury: Mitochondrial Biogenesis as a Potential Pharmacological Target.The Journal of pharmacology and experimental therapeutics · 2017Review
- Effects of intermittent ladder-climbing exercise training on mitochondrial biogenesis and endoplasmic reticulum stress of the cardiac muscle in obese middle-aged rats.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2017Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The selective type-3 phosphodiesterase inhibitor cilostazol and the antihyperlipidemic agent probucol have antioxidative, anti-inflammatory, and antiatherogenic properties. Moreover, cilostazol and probucol can regulate mitochondrial biogenesis. However, the combinatorial effect of cilostazol and probucol on mitochondrial biogenesis remains unknown. Endoplasmic reticulum (ER) stress is a well-known causative factor of nonalcoholic fatty liver disease (NAFLD) which can impair mitochondrial function in hepatocytes. Here, we investigated the synergistic effects of cilostazol and probucol on mitochondrial biogenesis and ER stress-induced hepatic steatosis. A synergistic effect of cilostazol and probucol on HO-1 and mitochondrial biogenesis gene expression was found in human hepatocellular carcinoma cells (HepG2) and murine primary hepatocytes. Furthermore, in an animal model of ER stress involving tunicamycin, combinatorial treatment with cilostazol and probucol significantly increased the expression of HO-1 and mitochondrial biogenesis-related genes and proteins, whereas it downregulated serum ALT, eIF2 phosphorylation, and CHOP expression, as well as the lipogenesis-related genes SREBP-1c and FAS. Based on these results, we conclude that cilostazol and probucol exhibit a synergistic effect on the activation of mitochondrial biogenesis via upregulation of HO-1, which confers protection against ER stress-induced hepatic steatosis.
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