Nonalcoholic fatty liver disease (NAFLD) is a complex hepato-metabolic syndrome with
multi-etiological pathways. No effective drugs have been settled for the effective therapy of
NAFLD. The purpose of this study was to investigate the modulatory effects of cilostazol (CILO,
50 and 100 mg/kg.p.o.) against NAFLD induced by high fat diet rich in cholesterol (HFD- CH)
for 10 weeks. Thirty male Sprague dawely rats were divided into 4 groups (8 rat / group).
Normal control group supplied with normal chow diet. Control positive group received high fat
diet rich in cholesterol for 10 weeks. In addition, two CILO groups received (CILO, 50 and 100
mg/kg.p.o.). Oral administration of (CILO; 100 mg/kg) showed promising results in reducing
fasting glucose and insulin levels. Moreover, CILO could reduce the elevated hepatic lipids,
oxidative stress biomarkers and inflammatory cytokines. In addition, CILO succeeded to restore
the total protein levels and activate nuclear factor erythroid-related factor 2/ heme oxygenase-1
(Nrf2/HO-1) activity. Furthermore, administration of CILO for NAFLD rats succeeded to show
corrected and normalized FTIR spectra. We also investigated the plausible binding interactions
of CILO with various biological targets using a molecular docking approach, and the results
showed that CILO had an excellent docking energy score and significant binding interactions
with the core amino acids involved in the active pocket for the enzymes studied. This study
depicts that CILO exerted new intervention for NAFLD due to its complementary antihyperlipdemic,
anti-inflammatory effects and antioxidant potential, via Nrf2/HO-1 activation.