Contents lists available at ScienceDirect Physiology & Behavior journal homepage: www.elsevier.com/locate/physbeh Linagliptin potentiates the effect of L-dopa on the behavioural, biochemical and immunohistochemical changes in experimentally-induced Parkinsonism: Role of toll-like receptor 4, TGF-β1, NF-κB and glucagon-like peptide 1 Ahmed M. Kabel a,b, ⁎ , Mohamed S. Omar c,d , A. Alhadhrami e , Salman S. Alharthi f , Majed M. Alrobaian g a Department of Clinical Pharmacy, College of Pharmacy, Taif University, Taif, Saudi Arabia b Pharmacology Department, Faculty of Medicine, Tanta University, Tanta, Egypt c Chemistry Department, Faculty of Science, Benha University, Benha, Egypt d Division of Biochemistry, Chemistry Department, Faculty of Science, Taif University, Taif, Saudi Arabia e Chemistry Department, Faculty of Science, Taif University, Taif, Saudi Arabia f Division of Analytical Chemistry, Chemistry Department, Faculty of Science, Taif University, Taif, Saudi Arabia g Department of Pharmaceutics, College of Pharmacy, Taif University, Taif, Saudi Arabia GRAPHICAL ABSTRACT ARTICLE INFO Keywords: Linagliptin L-dopa Carbidopa Parkinsonism Behavioural changes Mice ABSTRACT Objective: Our aim was to assess the effect of different doses of linagliptin with or without L-dopa/Carbidopa on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice. Methods: Eighty Balb/c mice were divided into 8 equal groups: Control; MPTP; MPTP + L-dopa/Carbidopa; MPTP + linagliptin 3 mg/kg/day; MPTP + linagliptin 10 mg/kg/day; MPTP + Carboxymethyl cellulose; MPTP + L-dopa/Carbidopa + linagliptin 3 mg/kg/day and MPTP + L-dopa/Carbidopa + linagliptin 10 mg/kg/ day. Striatal dopamine, tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), transforming growth factor beta 1 (TGF-β1), toll-like receptor 4 (TLR4), antioxidant enzymes, adenosine triphosphate (ATP), glucagon-like peptide-1 (GLP-1), receptors of advanced glycation end products (RAGE), nuclear factor (erythroid-derived 2)- like 2 (Nrf2), heme oxygenase-1 (HO-1), mitochondrial complex I activity, catalepsy and total swim scores were measured. Also, the substantia nigra was subjected to immunohistochemical examination. Results: The combination of L-dopa/Carbidopa and linagliptin in a dose-dependent manner resulted in significant https://doi.org/10.1016/j.physbeh.2018.01.028 Received 30 October 2017; Received in revised form 12 January 2018; Accepted 29 January 2018 ⁎ Corresponding author at: Department of Clinical Pharmacy, College of Pharmacy, Taif University, Al-Haweiah, P.O. Box 888, 21974, Saudi Arabia. E-mail address: ahmed.kabal@med.tanta.edu.eg (A.M. Kabel). Physiology & Behavior 188 (2018) 108–118 0031-9384/ © 2018 Elsevier Inc. All rights reserved. T