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.

Neuroprotective Effect of the Marine-Derived Compound 11-Dehydrosinulariolide through DJ-1-Related Pathway in In Vitro and In Vivo Models of Parkinson’s Disease

“…In our previous work, we only investigated 11-de protection of SH-SY5Y cells against 6-OHDA-induced damage via the PI3K/Akt pathway in an in vitro model [8]. However, our present study reveals that 11-de protects SH-SY5Y cell against 6-OHDA-induced cell damage via a DJ-1 modulated pathway that includes both the Akt/Nrf2 pathway and the Akt/CREB pathway.…”

“…In addition, Su et al (2012) revealed that 11-de induces apoptosis of A2058 cells through the dysregulation of mitochondria and the endoplasmic reticulum stress pathway [7]. Moreover, our previous study also indicated that 11-de protects neuronal-like cells against 6-OHDA-induced cytotoxicity through the PI3K/Akt pathway [8]. Liu et al (2011) used two-dimensional gel electrophoresis (2-DE) to show that 11-de upregulated DJ-1 protein expression [6].…”

Bioactive Marine Drugs and Marine Biomaterials for Brain Diseases

“…Moreover, pre-treatment with 11-dehydrosinulariolide (10 nM) also inhibited the down-regulation of phospho-Akt protein expression induced by 6-OHDA, as well as inhibited 6-OHDA-induced caspase-3/7 activation and 6-OHDA-induced translocation of NF-κB to the nucleus. 11-Dehydrosinulariolide (10 nM) inhibited the down-regulation of p-ERK induced by 6-OHDA [176]. The PI3K–Akt and ERK (p42/p44 mitogen-activated protein kinase) pathways are important factors in neuronal cell survival.…”

“…The PI3K–Akt and ERK (p42/p44 mitogen-activated protein kinase) pathways are important factors in neuronal cell survival. Their activation was suggested to have neuroprotective effects in PD [176]. AKT, a Ser/Thr protein kinase, regulates a variety of cellular processes, including cell survival, proliferation, protein translation and metabolism [177].…”

“…NF-κB is an inducible transcription factor that plays an important role in human inflammatory processes and various neurodegenerative diseases [179,180]. Moreover, the same authors [176] verified the in vivo effects of 11-dehydrosinulariolide, which was able to significantly attenuate the 6-OHDA-induced reduction of mean swimming velocity and total swimming distance in zebrafish.…”