title: Preventive effect of silymarin in cerebral ischemia-reperfusion-induced brain injury in rats possibly through impairing NF-κB and STAT-1 activation.
abstract: Silymarin and silibinin are bioactive components isolated from Silybum marianum. They have been reported to exhibit anti-oxidative and anti-inflammatory effects. Many studies revealed that drugs with potent anti-inflammatory potential can protect animals against inflammation-associated neurodegenerative disease, e.g., stroke. In this current work we established an animal model of acute ischemic stroke injury by inducing cerebral ischemic/reperfusion (CI/R) in rats to elucidate whether silymarin or silibinin can protect animals from CI/R injury. Pretreatment with silymarin, but not silibinin, dose-dependently (1-10μg/kg, i.v.) reduced CI/R-induced brain infarction by 16-40% and improved neurological deficits in rats with a stroke. Elevated pathophysiological biomarkers for CI/R-induced brain injury, including lipid peroxidation, protein nitrosylation, and oxidative stress, were all reduced by silymarin. In addition, expression of inflammation-associated proteins (e.g., inducible nitric oxide synthase, cyclooxygenase-2 and myeloperoxidase), and transcriptional factors (e.g., nuclear factor (NF)-kappa B and signal transducer and activator of transcription (STAT)-1), as well as production of proinflammatory cytokine (e.g., interleukin-1β and tumor necrosis factor-α) was all significantly prevented by silymarin. Furthermore, an in vitro study on microglial BV2 cells showed that silymarin could inhibit nitric oxide and superoxide anion production, possibly by interfering with NF-κB nuclear translocation/activation. Likewise, silymarin pretreatment also inhibited IκB-α degradation and NF-κB nuclear translocation in brain tissues of ischemic rats. Our results reveal that silymarin, but not its active component silibinin, protected rats against CI/R-induced stroke injury by amelioration of the oxidative and nitrosative stresses and inflammation-mediated tissue injury through impeding the activation of proinflammatory transcription factors (e.g., NF-κB and STAT-1) in the upregulation of proinflammatory proteins and cytokines in stroke-damaged sites. In conclusion, silymarin displays beneficial effects of preventing inflammation-related neurodegenerative disease, e.g., stroke, which needs further investigation and clinical evidences.
authors.affiliation: Department of Chinese Medicine, Taoyuan General Hospital, Department of Health, Department of Nursing, Yuanpei University, Hsinchu, Taiwan.
authors.forename: Yu-Chang
authors.initials: YC
authors.lastname: Hou
authors.forename: Kuo-Tong
authors.initials: KT
authors.lastname: Liou
authors.forename: Chang-Ming
authors.initials: CM
authors.lastname: Chern
authors.forename: Yea-Hwey
authors.initials: YH
authors.lastname: Wang
authors.forename: Jyh-Fei
authors.initials: JF
authors.lastname: Liao
authors.forename: Shiou
authors.initials: S
authors.lastname: Chang
authors.forename: Yuan-Hwa
authors.initials: YH
authors.lastname: Chou
authors.forename: Yuh-Chiang
authors.initials: YC
authors.lastname: Shen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D020520:Brain Infarction / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017628:Microglia / Q000187:drug effects; D020944:Silybum marianum / Q000737:chemistry*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors*; D012838:Silymarin / Q000494:pharmacology* / Q000627:therapeutic use; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D016328:NF-kappa B; D010936:Plant Extracts; D050794:STAT1 Transcription Factor; D012838:Silymarin