title: Silibinin attenuates MPP⁺-induced neurotoxicity in the substantia nigra in vivo.
abstract: Parkinson's disease (PD) is characterized by degeneration of the nigrostriatal dopaminergic (DA) pathway. The cause of neuronal death in PD is largely unknown, but it is becoming clear that inflammation plays a significant role in the pathophysiology of PD. Silibinin is a major flavonoid in milk thistle which has an anti-inflammatory activity. We investigated whether silibinin could have neuroprotective effects on DA neurons in the 1-methyl-4-phenylpyridinium ion (MPP(+))-treated animal model of PD in vivo. To address this question, animals received intraperitoneal (i.p.) injections 10, 50, or 100 mg/kg of silibinin, starting 1 day before MPP(+) injection and continued daily until 6 days post-lesion for tyrosine hydroxylase (TH) staining, or until 1 hour prior to the MPP(+) injection to examine the expression levels of inflammatory proteins. Finally, their brains were harvested at the indicated time points for the analyses. Silibinin treatment with 10 mg/kg had no significantly neuroprotective effects in the substantia nigra (SN). However, 50 and 100 mg/kg of silibinin ameliorated the MPP(+)-induced neurotoxicity in the SN in a dose-dependent manner, and the increased levels of inflammatory molecules such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) by MPP(+) treatment were attenuated by treatment with 100 mg/kg of silibinin. These results indicate that silibinin could be a useful and beneficial natural product offering promise for the prevention of DA neuronal degeneration involved in PD.
authors.affiliation: 1 Department of Food Science and Nutrition, Kyungpook National University , Daegu, Korea.
authors.forename: Un Ju
authors.initials: UJ
authors.lastname: Jung
authors.forename: Min-Tae
authors.initials: MT
authors.lastname: Jeon
authors.forename: Myung-Sook
authors.initials: MS
authors.lastname: Choi
authors.forename: Sang Ryong
authors.initials: SR
authors.lastname: Kim
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D053583:Interleukin-1beta / Q000032:analysis; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D010300:Parkinson Disease; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage*; D013378:Substantia Nigra / Q000737:chemistry / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
chemical_list: D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D000077385:Silybin; D052247:Nitric Oxide Synthase Type II; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium
keywords: Parkinson's disease; anti-inflammation; neurodegeneration; neuroprotection; silibinin