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Neuroprotection by marine-derived compound, 11-dehydrosinulariolide, in an in vitro Parkinson’s model: a promising candidate for the treatment of Parkinson’s disease

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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.

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Acknowledgments

The study was supported by research grants from Chang Gung Memorial Hospital (CMRPG881141) and the National Science Council of Taiwan (99-2313-B-110-003-MY03 and 100-2325-B-110-001).

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Authors and Affiliations

  1. Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan

    Wu-Fu Chen & Thung-Ming Su

  2. Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-Sen University, #70 Lien-Hai Rd, Kaohsiung, 804, Taiwan

    Chiranjib Chakraborty, Jyh-Horng Sheu & Zhi-Hong Wen

  3. Department of Anesthesiology, Veterans General Hospital, Taipei, 11217, Taiwan

    Chun-Sung Sung

  4. Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan

    Chien-Wei Feng, Yen-You Lin, Han-Chun Hung, Tzu-Yi Huang & Shi-Ying Huang

  5. Section of Orthopedic Surgery, Pingtung Christian Hospital, #60 Da-Lan Road, Pingtung, 900, Taiwan

    Yen-Hsuan Jean

  6. Taiwan Coral Research Center, National Museum of Marine Biology and Aquarium, Pingtung, 944, Taiwan

    Ping-Jyun Sung

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Correspondence to Zhi-Hong Wen.

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Chen, WF., Chakraborty, C., Sung, CS. et al. Neuroprotection by marine-derived compound, 11-dehydrosinulariolide, in an in vitro Parkinson’s model: a promising candidate for the treatment of Parkinson’s disease. Naunyn-Schmiedeberg's Arch Pharmacol 385, 265–275 (2012). https://doi.org/10.1007/s00210-011-0710-2

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