**Muhammad Ikram** †**, Kamran Saeed** †**, Amjad Khan, Tahir Muhammad, Muhammad Sohail Khan, Min Gi Jo, Shafiq Ur Rehman and Myeong Ok Kim \***

Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea; qazafi417@gnu.ac.kr (M.I.); kamran.biochem@gnu.ac.kr (K.S.); amjadkhan@gnu.ac.kr (A.K.); mtahir.khan@gnu.ac.kr (T.M.); sohail.bannu@gnu.ac.kr (M.S.K.); mingi.cho@gnu.ac.kr (M.G.J.); shafiq12@gnu.ac.kr (S.U.R.)

**\*** Correspondence: mokim@gnu.ac.kr; Tel.: +82-55-772-1345; Fax: +82-55-772-2656

Received: 3 April 2019; Accepted: 14 May 2019; Published: 15 May 2019

**Abstract:** The aim of the current study was to explore the underlying neuroprotective mechanisms of curcumin (50 mg/kg, for six weeks) against ethanol (5 mg/kg i.p., for six weeks) induced oxidative stress and inflammation-mediated cognitive dysfunction in mice. According to our findings, ethanol triggered reactive oxygen species (ROS), apoptosis, neuroinflammation, and memory impairment, which were significantly inhibited with the administration of curcumin, as assessed by ROS, lipid peroxidation (LPO), and Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/Heme-oxygenase-1) expression in the experimental mice brains. Moreover, curcumin regulated the expression of the glial cell markers in ethanol-treated mice brains, as analyzed by the relative expression TLR4 (Toll like Receptor 4), RAGE (Receptor for Advanced Glycations End products), GFAP (Glial fibrillary acidic protein), and Iba-1 (Ionized calcium binding adaptor molecule 1), through Western blot and confocal microscopic analysis. Moreover, our results showed that curcumin downregulated the expression of p-JNK (Phospo c-Jun N-Terminal Kinase), p-NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells), and its downstream targets, as assessed by Western blot and confocal microscopic analysis. Finally, the expression of synaptic proteins and the behavioral results also supported the hypothesis that curcumin may inhibit memory dysfunction and behavioral alterations associated with ethanol intoxication. Altogether, to the best of our knowledge, we believe that curcumin may serve as a potential, promising, and cheaply available neuroprotective compound against ethanol-associated neurodegenerative diseases.

**Keywords:** neurodegenerative diseases; oxidative stress; neuroinflammation; apoptosis; synaptic dysfunction
