Alzheimer's disease (AD) is one of the most common chronic neurodegenerative diseases and is associated with two types of pathological hallmarks in the brain. These biomarkers are extracellular plaque deposits mainly composed by amyloid-beta (Aβ) peptides and intracellular neurofibrillary tangles (NFT) formed by tau hyperphosphorylation [1]. Aβ peptides are deposited through enzymatic cleavage of amyloid precursor protein (APP) by β and γ-secretase enzymes [2]. In 2017, the Alzheimer's Association surveyed the AD population worldwide and found 48 million people with early symptoms of the disease. The prevalence of the disease is expected to double by 2050. The most common symptoms are short-term memory loss, difficulty in finding words, trouble with visual-spatial understanding, reasoning, judgment and insight.Reactive oxygen species (ROS) are the major key molecules in neurodegenerative diseases. Hydrogen peroxide (H 2 O 2 ) exposure in cultured neuronal cells would cause an imbalance of ROS production and scavenging activities. This process could be widely used to study this oxidative stress inducer in cell line models [3]. H 2 O 2induced oxidative stress can cause hyperphosphorylation in tau protein and induce formation of toxic neurofibrillary tangles in the brain cells [4]. In addition, all-trans-retinoic acid (RA) induction would enhance the neuronal morphological differentiation of SH-SY5Y cells and augment Alzheimer's disease markers such as tau and GSK3-β expression [5]. Hence, H 2 O 2 -induced pathogenicity and RA differentiation in SH-SY5Y cells could serve as a suitable model system for studying neuronal cell degeneration. Epalrestat (EPS) is a brain penetrant aldose reductase inhibitor, an approved drug currently used for the treatment of diabetic neuropathy. At near-plasma concentration, EPS induces glutathione biosynthesis, which in turn reduces oxidative stress in the neuronal cells. In this study, we found that EPS reduces neurodegeneration by inhibiting reactive oxygen species (ROS)-induced oxidative injury, mitochondrial membrane damage, apoptosis and tauopathy. EPS treatment up to 50 μM did not show any toxic effect on SH-SY5Y cell line (neuroblastoma cells). However, we observed toxic effect at a concentration of 100 μM and above. At 50 μM concentration, EPS showed better antioxidant activity against H 2 O 2 (100 μM)-induced cytotoxicity, ROS formation and mitochondrial membrane damage in retinoic acid-differentiated SH-SY5Y cell line. Furthermore, our study revealed that 50 μM of EPS concentration reduced the glycogen synthase kinase-3 β (GSK3-β) expression and total tau protein level in H 2 O 2 (100 μM)-treated cells. Findings from this study confirms the therapeutic efficacy of EPS on regulating Alzheimer's disease (AD) by regulating GSK3β and total tau proteins phosphorylation, which helped to restore the cellular viability. This process could also reduce toxic fibrillary tangle formation and disease progression of AD. Therefore, it is our view that an optimal concentration of EPS therapy...
The sulfated polysaccharide fucoidan was extracted from brown algae Turbinaria conoides using hot water and purified by anion‐exchange chromatography. The biochemical and monosaccharide composition of purified fucoidan was studied by colorimetric assays and Gas Chromatography Mass Spectrometry (GCMS). The purity of fucoidan was confirmed by agarose gel electrophoresis and the structure was characterized by using spectroscopic techniques such as Fourier transform infrared spectroscopy (FT‐IR) and solid‐state nuclear magnetic resonance (NMR) techniques. Further, the bioactivity properties of fucoidan such as antioxidant, anticoagulant and anti‐inflammatory were evaluated. The results showed profound antioxidant and anti‐inflammatory activities of fucoidan. The anti‐coagulant activity of fucoidan demonstrated striking inhibition of intrinsic and extrinsic coagulants involved in coagulation pathway.
Seaweed’s are abundant reservoir for biologically active molecules with antioxidant, anti-inflammatory, antiapoptotic and protease inhibition activities. The multifunctional properties of glycosides from seaweed could be utilized to treat diverse pathologic aetiologies of various human diseases. There are many pathological implications, of which the neurodegeneration is a relentless neurological disorder, which is characterized by progressive atrophy in the nervous system. Reports on the use of bioactive molecules from the seaweeds for the neurodegeneration is least explored. The present study characterizes the therapeutically important active molecule from the methanolic extracts of Turbinaria ornata and was used to assess the neurological progressive atrophy ability of the same. Two major fractions, MWTO (Methanol: Water (1:1) fraction from T. ornata) and MTO (Methanol fraction from T. ornata) were purified and eluted by column chromatography and the functional group was found to be glycoside’s. The MWTO fraction showed promising antioxidant, anti-proteolytic, anti-haemolytic and anticoagulant properties compared to the MTO fraction. The acetylcholine and butyrylcholine esterase inhibition activity of the MWTO were observed as 92.21% and 54.45% at 250µg, respectively. The in-vitro study revealed that MWTO could prevent cytotoxicity and ROS formation in SH-SY5Y cells and significantly enhance the cell proliferation (50%), thus could halt the progressive atrophy of the disease in the neurons. Later, MWTO was subjected to chemical characterization by UHPLC-ESI/MS and predicted the aglycone molecule of triterpenoid Oleanolic acid with the deprotonated molecular mass of 455m/z. Therefore, the therapeutically active MWTO could be used to combat neurodegeneration and related diseases.
Marine macroalgae are abundant reservoir for biologically active molecules with antioxidant, anti-inflammatory, antiapoptotic and protease inhibition activities. Neurodegeneration is a relentless neurological disorder which is characterized by progressive atrophy in the nervous system. The multifunctional properties of glycosides from macroalgae could be utilized to treat diverse pathologic aetiologies of various human diseases. The study aimed to characterize the therapeutically effective flavonol glycosides from methanolic extracts of Turbinaria ornata to prevent neurologic progressive atrophy. Subsequently the two major fractions of methanolic extracts (i.e. MWTO, fraction from 50% methanol and MTO, fraction from absolute methanol) were purified and eluted through column chromatography and confined as glycosides. MWTO fraction showed effective antioxidant, anti-proteolytic, anti-haemolytic and anticoagulant activities than MTO fraction. MWTO also exhibited promising acetylcholine and butyrylcholine esterase inhibition activities. The in-vitro study revealed that MWTO could prevent cytotoxicity and ROS formation in SH-SY5Y neuroblastoma cells and significantly enhance the cell proliferation, thus could halt the progressive atrophy of the disease in the neurons. Later, MWTO was subjected to chemical characterization by HPLC, FTIR and UHPLC-ESI/MS and predicted the aglycone molecule of flavonol glycoside as oleanolic acid. Therefore, the active therapeutic flavonol glycoside from MWTO could be used to combat neurodegeneration and related diseases.
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