title: Protective effects of Forsythia suspense extract with antioxidant and anti-inflammatory properties in a model of rotenone induced neurotoxicity.
abstract: The present study investigated the neuroprotective effects of Forsythia suspense extract in a rotenone-induced neurotoxic model. FS8, one of the herbal extracts, markedly protected PC12 cells against rotenone toxicity and was selected for the in vivo study. Gavage administration of FS8 (50 and 200mg/kg, but not 10mg/kg) for 25 days significantly improved the behavior function, decreased the loss of dopaminergic neurons in substantia nigra (SN), and maintained the level of dopamine in striatum after unilateral infusion of rotenone in SN. Wherein, the protective effects of FS8 at the dose of 200mg/kg were better than selegiline. Further study indicated the excellent antioxidant activity of FS8 on the 5th and 21st days after intranigral injection of rotenone. Moreover, FS8 could inhibit microglia activity and accumulation in SN, and obviously decreased the expression of pro-inflammatory molecules (IL-6, TNF-α, iNOS and COX-2), which indicated the anti-inflammatory effects of FS8. In the PI3K/Akt/NF-κB and MAPK pathways, FS8 significantly down-regulated the protein expression of p-PI3K, p-Akt, p-IκB, p-P65, cleaved Caspase 8, p-p38 and p-JNK but not p-mTOR, cleaved Caspase 3 and p-ERK. Therefore, FS8 protected dopamine neurons against rotenone toxicity via antioxidant and anti-inflammatory effects, which suggested the promising application of FS8 in the prevention and treatment of Parkinson disease.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Shao
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Xiu-Yun
authors.initials: XY
authors.lastname: Song
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Cong-Yuan
authors.initials: CY
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: pczhang@imm.ac.cn.
authors.forename: Pei-Cheng
authors.initials: PC
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Hunan University of Chinese Medicine, Changsha 410208, China. Electronic address: chennh@imm.ac.cn.
authors.forename: Nai-Hong
authors.initials: NH
authors.lastname: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D031657:Forsythia / Q000737:chemistry*; D005638:Fruit / Q000737:chemistry; D018836:Inflammation Mediators / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D016716:PC12 Cells; D010936:Plant Extracts / Q000009:adverse effects / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D045442:Rotarod Performance Test; D012402:Rotenone / Q000037:antagonists & inhibitors / Q000633:toxicity*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D010936:Plant Extracts; D012402:Rotenone; D001058:Apomorphine; D004298:Dopamine
keywords: Forsythia suspense; Inflammation; Neuroprotective; Parkinson disease; Rotenone