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 daily 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 anti-hyperlipdemic, anti-inflammatory effects and
antioxidant potential, via Nrf2/HO-1 activation.