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

Abstract

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.

Mitigating effect of ferulic acid on di-(2-ethylhexyl) phthalate-induced neurocognitive dysfunction in male rats with a comprehensive in silico survey

“…One of our interesting findings in the current study was the IR spectra retrieved from FTIR analysis. FTIR spectroscopy is a reliable biophysical tool that provides strong insight into macromolecule functional and structural alterations within tissue cells (Sedik and Amer 2022 ). In our study, we applied FTIR spectroscopy to investigate the neurotoxicity induced by DEHP in different animal groups and evaluate the role of FA to counteract the harmful effects of DEHP.…”