title: Neuroprotection by marine-derived compound, 11-dehydrosinulariolide, in an in vitro Parkinson's model: a promising candidate for the treatment of Parkinson's disease.
abstract: Parkinson's disease (PD) is a neurodegenerative disease characterized by tremor, rigidity, bradykinesia, and gait impairment. So far, very few pharmacological agents have been isolated or developed that effectively inhibit the progression of PD. However, several studies have demonstrated that inflammatory processes play critical roles in PD. Therefore, anti-inflammatory agents may suppress disease progression in PD. 11-Dehydrosinulariolide was isolated from cultured soft corals. The anti-inflammatory effect of this molecule has been observed through suppression of the expression of two main pro-inflammatory proteins: inducible nitric oxide synthase and cyclooxygenase-2, in lipopolysaccharide-stimulated macrophage cells. We also found that 11-dehydrosinulariolide significantly reduced 6-hydroxydopamine (6-OHDA)-induced cytotoxicity and apoptosis in a human neuroblastoma cell line (SH-SY5Y). The pharmacological activity of this compound has been studied, and it is associated with the inhibition of 6-OHDA-induced activation of caspase-3 and translocation of nuclear factor kappa B. 11-Dehydrosinulariolide increased the activation of survival-signaling phospho-Akt but not phospho-ERK. The neuroprotective effect of 11-dehydrosinulariolide was assessed here using 6-OHDA-treated SH-SY5Y cells, wherein neuroprotection is mediated through regulation of phosphatidylinositol 3-kinase (PI3K). Furthermore, 11-dehydrosinulariolide caused a significant decrease in caspase-3/7 activity in comparison to the 6-OHDA-treated group, indicating that 11-dehydrosinulariolide has neuroprotective properties. We conclude that 11-dehydrosinulariolide is a promising candidate for the treatment of Parkinson's disease through its anti-apoptotic and anti-inflammatory action via PI3K signaling.
authors: Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan.
authors: Wu-Fu
authors: WF
authors: Chen
authors: Chiranjib
authors: C
authors: Chakraborty
authors: Chun-Sung
authors: CS
authors: Sung
authors: Chien-Wei
authors: CW
authors: Feng
authors: Yen-Hsuan
authors: YH
authors: Jean
authors: Yen-You
authors: YY
authors: Lin
authors: Han-Chun
authors: HC
authors: Hung
authors: Tzu-Yi
authors: TY
authors: Huang
authors: Shi-Ying
authors: SY
authors: Huang
authors: Thung-Ming
authors: TM
authors: Su
authors: Ping-Jyun
authors: PJ
authors: Sung
authors: Jyh-Horng
authors: JH
authors: Sheu
authors: Zhi-Hong
authors: ZH
authors: Wen
mesh_terms: D000818:Animals; D037421:Anthozoa; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: C569844:11-dehydrosinulariolide; D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D018696:Neuroprotective Agents; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3