Abstract:
Diminished antioxidant defence or increased production of reactive oxygen species in the biological system can result in oxidative stress which could lead to various neurodegenerative diseases including Alzheimer’s disease (AD). Microglial activation also contributes to the progression of AD by producing several pro-inflammatory cytokines and mediators. Seaweeds have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties. This study aimed to evaluate the potential of brown (Padina australis and Sargassum polycystum) and green (Caulerpa racemosa) Malaysian seaweeds in inhibiting oxidative stress and neuroinflammation. Anti-oxidative activities of seaweeds were determined by measuring the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical and superoxide anion radical. Production of cytokines and PGE2 was measured using enzyme immunoassay and NO was measured using Griess reagent assay. In addition, cytotoxicity assays were conducted using MTT assay. Hexane extract of S. polycystum exhibited potent DPPH radical scavenging ability (IC50 0.16±0.00 mg/mL) and methanol extract of S. polycystum exhibited potent ABTS radical scavenging ability (IC50 0.85±0.02 mg/mL). Hexane extract of C. racemosa showed the strongest superoxide radical inhibitory effect (IC50 0.39±0.01 mg/mL). All extracts of P. australis, S. polycystum and C. racemosa significantly (P<0.05) reduced the production of PGE2, NO, TNF-α, IL-β and IL-6 in a dose dependent manner. At a concentration of α, IL-1β, IL-6) production and approximately more than 50% of NO production. PGE2 secretion was only suppressed by 20-30%. Isolation and structure elucidation of the seaweed compounds were evaluated using mass spectrometer, 1H and 13C Nuclear Magnetic Resonance Spectrometer. Hexane and dichloromethane extracts of S. polcystum and dichloromethane extract of P. australis afforded the same sterol identified as fucosterol and a pigment identified as pheophytin a. Another pigment identified as 132-hydroxy pheophytin a was isolated from methanol extract of S. polycystum. Hexane, dichloromethane and methanol extract of C. racemosa afforded one alkaloid which was identified as caulerpin. Pheophytin a showed the highest DPPH radical scavenging activity with the lowest IC50 value (0.14±0.01mg/mL). All of the seaweed compounds significantly (P<0.05) inhibited the production of PGE2, NO, TNF-α, IL-β and IL-6 in a dose dependent manner. Caulerpin inhibited 60-70% of cytokines, PGE2 and NO. As a conclusion, this study supports the potential application of these seaweeds for the treatment of AD.
