Assessment of anti-amyloidogenic activity of marine red alga G. acerosa against Alzheimer's beta-amyloid peptide 25-35.

OBJECTIVE: The amyloid hypothesis stimulates the discovery of compounds, which promotes beta-amyloid peptide (Aß) clearance, thereby altering the underlying pathophysiology of Alzheimer's disease (AD). Hence, the present study aims at the evaluation of anti-amyloidogenic potential of Gelidiella acerosa. METHODS: Prevention of Aß 25-35 aggregate formation and disaggregation of pre-formed fibrils by G. acerosa was evaluated in three phases by thioflavin T spectrophotometric assay. The results were further validated by confocal microscopic analysis. The conformational changes in the aggregated and non-aggregated Aß in the presence of G. acerosa were analyzed by Fourier transform infrared (FTIR) spectroscopic analysis. RESULTS: Phase-I study shows that G. acerosa reverts (4.56 ± 0.35 AU at 96 hours) the increase in fluorescence intensity of aggregated Aß (18.76 ± 0.99 AU) significantly (P < 0.05) as that of non-aggregated peptides, which suggests that G. acerosa prevents the formation of oligomers from monomers. The seaweed also prevents the fibril formation even after the aggregation process was initiated at 20 hours, which was verified by the significant (P < 0.05) decrease in the fluorescence intensity (2.94 ± 0.0721 AU) at 36 hours (Phase II). In addition, G. acerosa promotes fibrillar destabilization (Phase III), which was further substantiated by confocal microscopic analysis. Fourier transform infrared spectroscopy reveals that alteration in amide I and amide II band spectrum, which occurs due to Aß 25-35 aggregation was restored upon co-treatment with G. acerosa benzene extract. CONCLUSION: Overall, the results suggest that G. acerosa might have direct interaction with the aggregated peptide, thereby preventing oligomerization and fibrillation of Aß 25-35.

Assessment of mutagenic effect of G. acerosa and S. wightii in S. typhimurium (TA 98, TA 100, and TA 1538 strains) and evaluation of their cytotoxic and genotoxic effect in human mononuclear cells: a non-clinical study.

The marine red algae (Gelidiella acerosa and Sargassum wightii) possessing excellent antioxidant and anticholinesterase activity were subjected to toxicity evaluation for a deeper understanding of other bioprotective properties of seaweeds. Cytotoxic evaluation was done by trypan blue exclusion, and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays using human PBMC (peripheral blood mononuclear cells) and RBC (red blood cells) lysis assay using human erythrocytes. Mutagenicity of the seaweeds was analyzed by Ames salmonella mutagenicity test with the histidine dependent mutant strains TA 98, TA100 and TA 1538. Genotoxic activity was verified in PBMC by comet assay. The results suggest that benzene extract of G. acerosa (BEGA) and dichloromethane extract of S. wightii (DMESW) did not show cytotoxic effect both in PBMC and erythrocytes. Evaluation of mutagenic activity suggests that the seaweeds did not cause any mutagenic effects both in the absence and the presence of S9 microsomal fraction in all the three Salmonella mutant strains. Results of genotoxic study showed that PBMC treated with seaweed extracts (1 mg/mL) exhibit less or no damage to cells, thus proving the non-genotoxic effect of the extract. Since these in vitro non-clinical studies clearly demonstrate the non-toxic nature of the seaweeds, they could be exploited for further characterization, which would result in development of novel and safe therapeutic entities.

Assessment of Anticholinesterase Activity of Gelidiella acerosa: Implications for Its Therapeutic Potential against Alzheimer's Disease.

The effect of various solvent extracts of Gelidiella acerosa on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities was investigated. AChE and BuChE inhibitory activities were analyzed by spectrophotometric method. Phytochemical screening of the compounds present in the solvent extracts was done qualitatively. Characterization of the compounds present in the benzene extract of G. acerosa was done by GC-MS analysis. The results showed that, at 487.80 µg/mL, benzene extract showed significant (P < 0.05) inhibitory activity against both AChE and BuChE with the percentage of inhibition 54.18 ± 5.65 % (IC(50) = 434.61 ± 26.53 µg/mL) and 78.43 ± 0% (IC(50) = 163.01 ± 85.35 µg/mL), respectively. The mode of inhibition exhibited by benzene extract against the AChE and BuChE was found to be competitive and uncompetitive type of inhibition, respectively. Preliminary phytochemical analysis coupled with GC-MS illustrates that the benzene extract possesses high amount of terpenoids, which could be the reason for potential cholinesterase inhibitory activity.