Sawsan A Zaitone1, Eman Ahmed2, Nehal M Elsherbiny3, Eman T Mehanna4, Mohammed K El-Kherbetawy5, Mohamed H ElSayed6, Duha M Alshareef7, Yasser M Moustafa8. 1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt. Electronic address: szaitone@ut.edu.sa. 2. Clinical Pharmacology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. 3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. 4. Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt. 5. Department of Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. 6. Department of Physiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. 7. Department of Pharmaceutics, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. 8. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
Abstract
BACKGROUND: Caffeic acid phenethyl ester is found in honey bee propolis. It has immunomodulatory, anti-inflammatory and anti-cancer properties. Rotenone is a pesticide commonly used for inducing experimental Parkinson's disease (PD) due to complex I inhibition and microglia activating properties. The current study examined neuroprotective effect of caffeic acid against rotenone-induced neurodegeneration in groups of seven mice. METHODS: Mice received protective doses of caffeic acid (2.5, 5 or 10 mg/kg) daily and nine injections of rotenone (1 mg kg, subcutaneously) - every 48 h. Behavioral evaluation of motor function was done by a battery of tests including open-field test, cylinder test, pole test and rotarod test; all these tests showed motor impairment. RESULTS: Assay of striatal dopamine highlighted a significant decrease and increases in inflammatory markers. In addition, histopathological assessment of substantia nigra neurons demonstrated low immunostaining for tyrosine hydroxylase (TH) in rotenone treated mice. PCR analysis highlighted upregulation for genes encoding CD11b (a microglia surface antigen), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NFκB). Treatment with caffeic acid (5 or 10 mg/kg) amended most of rotenone-induced motor deficits, lessened microglia expression and inflammatory mediators and improved the nigral TH immunostaining. CONCLUSION: These results confirmed the anti-inflammatory activity of caffeic acid and highlighted its neuroprotective activity against rotenone-induced neurodegeneration in mice.
BACKGROUND:Caffeic acid phenethyl ester is found in honey bee propolis. It has immunomodulatory, anti-inflammatory and anti-cancer properties. Rotenone is a pesticide commonly used for inducing experimental Parkinson's disease (PD) due to complex I inhibition and microglia activating properties. The current study examined neuroprotective effect of caffeic acid against rotenone-induced neurodegeneration in groups of seven mice. METHODS:Mice received protective doses of caffeic acid (2.5, 5 or 10 mg/kg) daily and nine injections of rotenone (1 mg kg, subcutaneously) - every 48 h. Behavioral evaluation of motor function was done by a battery of tests including open-field test, cylinder test, pole test and rotarod test; all these tests showed motor impairment. RESULTS: Assay of striatal dopamine highlighted a significant decrease and increases in inflammatory markers. In addition, histopathological assessment of substantia nigra neurons demonstrated low immunostaining for tyrosine hydroxylase (TH) in rotenone treated mice. PCR analysis highlighted upregulation for genes encoding CD11b (a microglia surface antigen), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NFκB). Treatment with caffeic acid (5 or 10 mg/kg) amended most of rotenone-induced motor deficits, lessened microglia expression and inflammatory mediators and improved the nigral TH immunostaining. CONCLUSION: These results confirmed the anti-inflammatory activity of caffeic acid and highlighted its neuroprotective activity against rotenone-induced neurodegeneration in mice.
Authors: Valeria C Gonçalves; Daniel J L L Pinheiro; Tomás de la Rosa; Antônio-Carlos G de Almeida; Fúlvio A Scorza; Carla A Scorza Journal: Nutrients Date: 2020-05-26 Impact factor: 5.717