title: Therapeutic effects of paeonol on methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid-induced Parkinson's disease in mice.
abstract: Paeonol is a major phenolic compound of the Chinese herb, Cortex Moutan, and is known for its antioxidant, anti-inflammatory and antitumor properties. The present study was designed to investigate the therapeutic potential and underlying mechanisms of paeonol on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p)-induced mouse model of Parkinson's disease (PD). MPTP (25 mg/kg), followed by probenecid (250 mg/kg), was administered via i.p. injection for five consecutive days to induce the mouse model of PD. Paeonol (20 mg/kg) was administrated orally for 21 days. Behavior was assessed using the rotarod performance and open‑field tests. Additionally, the levels of tyrosine hydroxylase (TH), microglia, interleukin‑1β (IL‑1β), and brain‑derived neurotrophic factor (BDNF) in the substantia nigra pars compacta (SNpc) were evaluated by immunohistochemical staining. MPTP/p‑induced motor deficits were observed to be significantly improved following long‑term treatment with paeonol. Paeonol treatment decreased MPTP/p‑induced oxidative stress, as determined by evaluating the activity levels of superoxide dismutase, catalase and glutathione. Additionally, MPTP/p‑induced neuroinflammation was assessed by examining the levels of microglia and IL‑1β, which were significantly decreased following paeonol treatment. Paeonol treatment improved the MPTP/p‑induced dopaminergic neurodegeneration, as measured by observing the increased TH level in the SNpc. Furthermore, the BDNF level was significantly elevated in the paeonol treatment group compared with mice treated with MPTP/p only. In conclusion, paeonol exerted therapeutic effects in the MPTP/p‑induced mouse model of PD, possibly by decreasing the damage from oxidative stress and neuroinflammation, and by enhancing the neurotrophic effect on dopaminergic neurons. The results demonstrate paeonol as a potential novel treatment for PD.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
authors.forename: Hong-Dang
authors.initials: HD
authors.lastname: Qu
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D000098:Acetophenones / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D011339:Probenecid / Q000009:adverse effects*; D045442:Rotarod Performance Test; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000098:Acetophenones; D019208:Brain-Derived Neurotrophic Factor; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; C013638:paeonol; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D011339:Probenecid