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Context: Sargassum has been used in traditional Chinese medicine since the eighth century AD to treat goiter. Sargassum wightii Greville (Sargassaceae) is a major source of alginic acid used widely in food and drug industries. Objective: To evaluate the anti-Alzheimer potential of S. wightii through evaluation of antioxidant and cholinesterase inhibitory activities. Materials and methods: Successive extraction was done using solvents of varying polarity. Solvent extracts (100-500 mg/mL) were employed for all the antioxidant assays. Free radical scavenging activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl, OH. , H 2 O 2 radical scavenging assay. The reducing power of the seaweed was evaluated by ferric reducing antioxidant power and reducing power assay. Cholinesterase (ChE) inhibitory activity was evaluated and the Km, Vmax and Ki were calculated. Further, compound characterization was done by GC-MS analysis. Results: The non-polar extracts were found to possess significant antioxidant activity. At 100 mg/mL, petroleum ether, hexane, benzene and dichloromethane extracts showed significant ChE inhibitory activity with IC 50 values of 19.33 AE 0.56, 46.81 AE 1.62, 27.24 AE 0.90, 50.56 AE 0.90 mg/mL, respectively, for AChE, and 17.91 AE 0.65, 32.75 AE 1.00, 12.98 AE 0.31, 36.16 AE 0.64 mg/mL, respectively, for BuChE. GC-MS reveals that 1,2-benzenedicarboxylic acid, diisooctyl ester is the major compound present in dichloromethane extract of S. wightii. The mode of inhibition exhibited by dichloromethane extract against the cholinesterases was found to be competitive type. Discussion and conclusion: The presence of high amount of terpenoids could be the possible reason for its potential antioxidant and ChE inhibitory activity.

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 % (IC50 = 434.61 ± 26.53 μg/mL) and 78.43 ± 0% (IC50 = 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.

Context Gelidiella acerosa (Forsskål) Feldmann & G. Hamel (Rhodophyta-Gelidiales) is a marine red macroalga. Our previous work found that a benzene extract of G. acerosa possesses noticeable neuroprotective activity, when evaluated through in vitro and in vivo systems. Objective Bioactive-guided fractionation and identification of active compounds by column chromatography using solvents of varying polarity. Materials and methods Fractionation was done by column chromatography, antioxidant and anticholinesterase activity was assessed by DPPH and cholinesterase inhibition assays (50-200 mg/ml), compound identification was done by LC-MS analysis, the mode of interaction of active compound was analyzed through docking studies and quantification was done by highperformance thin-layer chromatography (HPTLC) analysis.Results The results suggest that fractions F9-F13 exhibited significant (p50.05) antioxidant and anticholinesterase activities. Hence, these fractions were pooled together and verified for neuroprotective activity. The pooled fraction was subjected to LC-MS analysis and among all the compounds, phytol was previously reported to possess excellent neuroprotective potential. Hence, the neuroprotective potential of phytol was assessed. The results suggest that phytol showed significant (p50.05) antioxidant activities (25-125 mg/ml) with an IC 50 value of 95.27 ± 1.65 mg/ml and cholinesterase inhibitory potential (5-25 mg/ml) with IC 50 values of 2.704 ± 0.07 and 5.798 ± 0.72 mg/ml for AChE and BuChE, respectively. Molecular docking studies suggest that phytol interacts with cholinesterase through the arginine residue of the enzyme. HPTLC quantification showed that about 6.266 mg of phytol was present per mg of pooled fraction. Conclusion The study suggests that phytol might act as the key compound in contributing to the neuroprotective potential of G. acerosa. ARTICLE HISTORY

Alzheimer's disease is an age-related, complex neurodegenerative disorder characterized by loss of memory and impairment of multiple cognitive functions. Several factors contribute to the progression and development of the disease including amyloid beta accumulation, neurofibrillary tangle formation, cholinergic deficit, oxidative stress, neuroinflammation, and apoptosis. Numerous traditional and herbal medicinal plants have been used to treat several cognitive disorders including Alzheimer's disease. They act as excellent antioxidants, anti-inflammatory mediators, and cholinesterase and β-secretase inhibitors. In addition, these natural compounds also prevent the accumulation of amyloid beta and its fibril formation. Besides acting as core-molecules, these natural compounds act as a template for the production and synthesis of several drug leads with improved pharmacokinetic potentials and greater efficacies. Hence, herbal medicines that have interesting pharmacological effects with noticeable anti-Alzheimer's potential deserve increased attention for further development to drug entities. The present article reviews the botanical pharmacology with special reference to anti-Alzheimer activity of plants and plant-derived compounds.

Overall, the results suggest that G. acerosa might have direct interaction with the aggregated peptide, thereby preventing oligomerization and fibrillation of Aβ 25-35.

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.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with multiple pathological consequences such as oxidative stress, inflammation, apoptosis, cholinergic deficit, amyloid plaques, and tangles formation. Hence, development of drugs with multiple targets will be effective in the treatment of AD. The present study aims at evaluation of the neuroprotective effect of Gelidiella acerosa against amyloid beta 25-35 (Aβ 25-35) induced toxicity in PC12 cells. The antioxidative effect was evaluated by monitoring levels of antioxidant enzymes. Protection against ROS-induced damage was assessed by the measurement of lipid peroxidation, protein carbonyl content (PCC), 2',7'-dichlorofluorescein diacetate (DCFH-DA) fluorescence, and nitric oxide (NO) production. The cholinesterase (ChE) inhibitory activity was also evaluated. The antiapoptotic activity was verified by caspase-3 activity. The results of antioxidant assays suggest that G. acerosa significantly (P < .05) restores the levels of antioxidant enzymes. Moreover, the seaweed extract was found to prevent the formation of intracellular ROS induced by Aβ 25-35 and thereby protects PC12 cells from macromolecular damage. The study demonstrated that G. acerosa inhibits ChE activity significantly (P < .05) in PC12 cells. The significant decrease (P < .05) in the level of caspase-3 activity indicates that the seaweed has anti-apoptotic activity. Hence, the outcome of this study signifies the neuroprotective effect of G. acerosa targeting multiple pathological consequences of AD.