Modulatory Effects of Cilostazol; an Nrf2/HO-1 activator against NAFLD in Rats Confirmed by Molecular Docking and FTIR Studies

Nonalcoholic fatty liver disease (NAFLD) is a complex hepato-metabolic syndrome withmulti-etiological pathways. No effective drugs have been settled for the effective therapy ofNAFLD. 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 fatdiet rich in cholesterol for 10 weeks. In addition, two CILO groups received (CILO, 50 and 100mg/kg.p.o.). Oral administration of (CILO; 100 mg/kg) showed promising results in reducingfasting glucose and insulin levels. Moreover, CILO could reduce the elevated hepatic lipids,oxidative stress biomarkers and inflammatory cytokines. In addition, CILO succeeded to restorethe 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 showcorrected and normalized FTIR spectra. We also investigated the plausible binding interactionsof CILO with various biological targets using a molecular docking approach, and the resultsshowed that CILO had an excellent docking energy score and significant binding interactionswith the core amino acids involved in the active pocket for the enzymes studied. This studydepicts that CILO exerted new intervention for NAFLD due to its complementary antihyperlipdemic,anti-inflammatory effects and antioxidant potential, via Nrf2/HO-1 activation.