Characterization of lactic acid bacteria derived exopolysaccharides for use as a defined neuroprotective agent against amyloid beta1–42-induced apoptosis in SH-SY5Y cells

Abstract

Alzheimer's disease (AD) is a disease characterized by cerebral neuronal degeneration and loss in a progressive manner. Amyloid beta (Aβ) in the brain is toxic to neurons, being a main risk factor for initiation and continuation of cognitive deterioration in AD. Neurotoxicity of Aβ origin is also linked to oxidative stress characterized by excessive lipid peroxidation, protein oxidation, changes in antioxidant systems, and cerebral DNA damage in AD. Furthermore, Aβ can induce oxidative neuronal cell death by a mitochondrial dysfunction. Cellular injury caused by oxidative stress can be possibly prevented by boosting or promoting bodily oxidative defense system by supplying antioxidants in diet or as medications. However, most synthetic antioxidants are found to have cytotoxicity, which prevents their safe use, and limits their administration. For this reason, more attention has been paid to the natural non-toxic antioxidants. One of the most promising groups of non-toxic antioxidative compounds is thought to be polysaccharides. This study investigated the characterization and protective action exerted by exopolysaccharides (EPSs) originated from Lactobacillus delbrueckii ssp. bulgaricus B3 and Lactobacillus plantarum GD2 to protect from apoptotic activity exerted by Aβ 1-42 among SH-SY5Y cells. We characterized EPSs by elemental analysis, FTIR, AFM, SEM, and XRD. The antioxidant effects of EPSs were determined by the DPPH free radical scavenging activity, hydroxyl radical scavenging activity, metal ion chelating activity, lipid peroxidation inhibitory activity, and superoxide anion scavenging activity method. The protective effects of EPSs were determined by flow cytometry and RT-PCR. Mannose ratio, molecular weight, functional groups, surface morphology, and amorphous character structure of EPSs are thought to play a role in the protective effect of EPSs. EPSs reduced apoptotic activity of Aβ 1-42 in addition to their depolarizing effect on mitochondrial membrane potential in concentration-dependent manner. These observations contribute the inclusion of EPSs among the therapeutic options used to manage various neurological disorders in the traditional medicine in a scientific manner, indicating that EPSs may be promising natural chemical constituents that need advanced research and development for pharmacological therapy of AD. Alzheimer's disease (AD) is a disease characterized by cerebral neuronal degeneration and loss in a progressive manner; these events show parallelism with two most striking neuropathological signs of AD, i.e. the formation of neurofibrillary tangles and senile plaques 1. Amyloid beta (Aβ) fibrils are formed in multiple steps, which follow the monomeric Aβs being oligomerized and aggregated, where the peptide goes through a conformational change from an alpha-helical to a beta-pleated sheet architecture. It has been recently shown that cerebral neurotoxicity arises from the effects of soluble oligomers of Aβ 2. Multiple studies both performed in vitro and in vivo have demonstrated that Aβ ...

Interplay of gut microbiota and oxidative stress: Perspective on neurodegeneration and neuroprotection

“…Similarly, it was reported that exopolysaccharides isolated from Lactobacillus delbrueckii ssp. bulgaricus B3 and Lactobacillus plantarum GD2 protected SH-SY5Y cells from Aβ(1–42)-induced apoptosis [22] , which potentiates their role as a promising natural chemical constituent for the pharmacological therapy of AD. Moreover, treatment of SH-SY5Y and mouse model with heat-killed strain of Rumnicoccus albus showed the neuroprotective effects, it was found to be very effective in reducing ROS levels and increasing superoxide dismutase (SOD) and glutathione (GSH) levels in hydrogen peroxide (H 2 O 2 ) treated SH-SY5Y cells and in sodium arsenate treated animal models [23] .…”

Natural Polysaccharides as Preventive and Therapeutic Horizon for Neurodegenerative Diseases

“…In addition, Aβ can, through mitochondrial dysfunction, induce oxidative neuronal cell death [26]. Sirin et al [146] investigated the possibility that exopolysaccharides (EPSs) originating from the Lactobacillus delbrueckii subsp. bulgaricus B3 and Lactobacillus plantarum GD2, protect SH-SY5Y cells from the apoptotic activity of Aβ1-42.…”

“…EPSs depolarized mitochondrial membrane potential and decreased the apoptotic activity of Aβ1-42 in a concentrationdependent manner. These results led to the addition of EPSs to traditional medicine recommendations for different neurological disorders [146].…”

Purification, Structural Characteristics, and Biological Activities of Exopolysaccharide Isolated From Leuconostoc mesenteroides SN-8

“…A large number of studies have shown that the EPS produced by LAB can exhibit diverse pharmacological activities such as acting as anticancer, antibacterial, and antioxidant, and thus it may have significant therapeutic potential. Moreover, EPS produced by LAB alone may not display significant toxicity toward the normal cells ( Sirin and Aslim, 2020 ). Figure 5 shows the inhibitory effect of different concentrations (1,000, 2,000, and 5,000 μg/mL) of EPS-8-2 against the growth of HepG2 cells.…”