Cilostazol

Momany EM Al , et al. Toxicology Reports, 2024, 13, 101814.

Cilostazol effectively mitigates carbamazepine-induced genotoxic and cytotoxic effects, highlighting its potential as a protective agent in therapeutic regimens involving carbamazepine.
Carbamazepine is known for its genotoxic and cytotoxic effects, particularly in human lymphocytes. Cilostazol's pharmacological versatility positions it as a potential protective agent against such adverse effects. The study utilized sister chromatid exchange (SCE) assays and cell kinetic evaluations to investigate the combined and individual impacts of these drugs. Genotoxicity was assessed through the frequency of SCEs, while cytotoxicity was evaluated using mitotic and proliferative indices in human cultured blood lymphocytes treated with carbamazepine, cilostazol, or their combination.
Carbamazepine significantly elevated SCE frequency and proliferative index (p<0.01), indicating enhanced genotoxic and cytotoxic activity. Conversely, cilostazol substantially reduced SCE frequency (p<0.01) and normalized the proliferative index. Remarkably, the combination of cilostazol and carbamazepine restored SCE and proliferative indices to control levels (p>0.05), suggesting a neutralization of carbamazepine's genotoxicity.

Gad ES, et al. European Journal of Pharmacology, 2025, 987, 177194.

Cilostazol demonstrates significant potential in ameliorating hepatic encephalopathy (HE) by restoring mitochondrial function, reducing neuroinflammation, and enhancing antioxidant capacity. Its ability to modulate key signaling pathways underscores its therapeutic value in managing HE and other neurodegenerative disorders.
HE is characterized by a complex interplay of hyperammonemia, oxidative stress, neuroinflammation, and mitochondrial dysfunction. Cilostazol, known for its antioxidant and anti-inflammatory properties, was evaluated for its ability to counteract these multifactorial processes by targeting the cAMP/AMPK/SIRT1 pathway. Rats were divided into three groups: normal control, thioacetamide (TAA)-induced HE, and Cilostazol-treated HE. The latter received 100 mg/kg/day of Cilostazol for six weeks, concurrently with TAA. Cognitive and motor performance, mitochondrial biogenesis, and inflammatory markers were analyzed.
Cilostazol improved cognitive and motor performance (p<0.0001), activated AMPK/SIRT1 signaling, and suppressed NF-κB-mediated inflammation. Additionally, it restored antioxidant defenses by upregulating Nrf2 and modulated mitochondrial dynamics via the PINK1/Parkin pathway. Enhanced neuroprotection was observed through increased BDNF/TrkB/p-CREB signaling and the regulation of apoptotic markers Bax and Bcl2.

Sahinturk S. Prostaglandins & Other Lipid Mediators, 2023, 169, 106782.

Cilostazol's vasorelaxant action is mediated by a complex interplay of endothelial, metabolic, and ionic mechanisms. Its ability to modulate vascular tone through eNOS activation and potassium channel regulation underscores its therapeutic potential in managing vascular dysfunction.
The study explored its mechanism of action using isolated rat thoracic aorta rings. Vessel rings were pre-contracted with potassium chloride or phenylephrine and exposed to cumulative concentrations of Cilostazol (10⁻⁸~10⁻⁴ M). Specific pathway inhibitors and ion channel blockers were employed to elucidate its mechanism.
Cilostazol induced concentration-dependent vasorelaxation (pD2: 5.94 ± 0.94, p<0.001). Key mechanisms included activation of the eNOS/NO/cGMP pathway and cyclooxygenase-derived prostanoids. Inhibition of AMPK, PKC, and potassium channels significantly attenuated its effect. Furthermore, Cilostazol blocked calcium influx and inhibited caffeine- and phorbol ester-induced vascular contractions.