Loliolide, a New Therapeutic Option for Neurological Diseases? In Vitro Neuroprotective and Anti-Inflammatory Activities of a Monoterpenoid Lactone Isolated from Codium tomentosum

  • Int J Mol Sci. 2021 Feb 14;22(4):1888. doi: 10.3390/ijms22041888.
Joana Silva  1  2 Celso Alves  1 Alice Martins  1 Patrícia Susano  1 Marco Simões  1 Miguel Guedes  1 Stephanie Rehfeldt  3 Susete Pinteus  1 Helena Gaspar  4 Américo Rodrigues  1 Márcia Ines Goettert  3 Amparo Alfonso  2 Rui Pedrosa  5
Affiliations
  • 1. MARE-Marine and Environmental Sciences Centre, Polytechnic of Leiria, 2520-630 Peniche, Portugal.
  • 2. Department of Pharmacology, Faculty of Veterinary, University of Santiago de Compostela, 27002 Lugo, Spain.
  • 3. Cell Culture Laboratory, Graduate Program in Biotechnology, University of Vale do Taquari (Univates), Lajeado, RS 95914-014, Brazil.
  • 4. BioISI-Biosystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisboa, Portugal.
  • 5. MARE-Marine and Environmental Sciences Centre, ESTM, Polytechnic of Leiria, 2520-614 Peniche, Portugal.
Abstract

Parkinsons Disease (PD) is the second most common neurodegenerative disease worldwide, and is characterized by a progressive degeneration of dopaminergic neurons. Without an effective treatment, it is crucial to find new therapeutic options to fight the neurodegenerative process, which may arise from marine resources. Accordingly, the goal of the present work was to evaluate the ability of the monoterpenoid lactone Loliolide, isolated from the green seaweed Codium tomentosum, to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells and their anti-inflammatory effects in RAW 264.7 macrophages. Loliolide was obtained from the diethyl ether extract, purified through column chromatography and identified by NMR spectroscopy. The neuroprotective effects were evaluated by the MTT method. Cells' exposure to 6-OHDA in the presence of Loliolide led to an increase of cells' viability in 40%, and this effect was mediated by mitochondrial protection, reduction of oxidative stress condition and Apoptosis, and inhibition of the NF-kB pathway. Additionally, Loliolide also suppressed nitric oxide production and inhibited the production of TNF-α and IL-6 pro-inflammatory cytokines. The results suggest that Loliolide can inspire the development of new neuroprotective therapeutic agents and thus, more detailed studies should be considered to validate its pharmacological potential.

Keywords
NF-kB pathway; Parkinson’s disease; antioxidant activity; inflammation; marine natural products; neuroprotection; oxidative stress; seaweeds.
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