Sodium deoxycholate

The inhibitory effects of bile acids on catalytic and noncatalytic functions of acetylcholinesterase as a therapeutic target in Alzheimer's disease.[Pubmed:32602852]

Acta Neurobiol Exp (Wars). 2020;80(2):108-116.

Acetylcholine is a fast-acting neurotransmitter in synapses and neuromuscular junctions that is decreased in Alzheimer's disease (AD) by hyperactivation of acetylcholinesterase (AChE), which leads to progressive loss of memory and neurobehavioral abnormalities. Therefore, AChE inhibitors have therapeutic potential in AD that could include natural compounds such as bile acids. Bile acids, as potent molecules, could improve some types of neurodegenerative diseases via antioxidant effects and other unknown mechanisms. The aim of this study was to investigate beneficial effects of bile acids on AChE catalytic and noncatalytic functions, amyloid plaque deposit and memory in a rat model of AD. The effects of Sodium deoxycholate and cholic acid on AChE activity were assessed by in vitro assay. Then, the bile acids' potential therapeutic effects were investigated on nucleus basalis of Meynert lesioned rats using behavioral evaluation, biochemical tests and histological methods. Molecular docking simulation was also implemented to investigate the possible interaction between bile acids and AChE. According to the in vitro and in vivo results, Sodium deoxycholate could efficiently inhibit the catalytic function of the enzyme by interacting with the catalytic site, while cholic acid interacted with the peripheral anionic site and inhibited chaperone activity of the enzyme that led to the reduced amyloid plaque deposition. The coadministration of cholic acid and Sodium deoxycholate showed these compounds are able to simultaneously inhibit the catalytic and noncatalytic functions of the enzyme. This study clarifies the roles of natural bile acids in the nervous system and in AChE function through multiple experimental and simulation methods.

Blends of sodium deoxycholate-based poly(ester ether)urethane ionomer and hydroxypropylcellulose with mucosal adhesiveness.[Pubmed:32585272]

Int J Biol Macromol. 2020 Jun 22. pii: S0141-8130(20)33634-5.

New mucoadhesive blends of Sodium deoxycholate-based poly(ester ether)urethane ionomer (PU) and hydroxypropyl cellulose (HPC) are prepared. The presence of the intermolecular interactions between the polymeric components has been investigated by FTIR spectroscopy indicating their miscibility in the solid phase. DSC studies also revealed a single glass transition of the blends, which is indicative of miscibility of PU and HPC in the amorphous phase. The amount of HPC in the blends influences strongly the physicochemical and mucoadhesion/bioadhesion properties. It was found that the value of area attributed to ordered hydrogen bonding (FTIR), the onset temperature values of thermal degradation in N2 flow (TG/DTG), the values of the sorption capacity (Dynamic Vapor Sorption-DVS), the values of the apparent viscosity (rheological measurements) and mucoadhesion/bioadhesion properties increased by increasing the HPC content in the blends. Complex viscosity revealed shear thinning behavior for all the studied solutions evidencing the contributive role of polymer viscoelasticity on mucoadhesion. It was found that both G' and G" increase with an increase in angular frequency and G">G' which is characteristic for liquid-like (sol state) behavior for all blended solutions and this behavior is helpful in the adhesion with mucosa surface. Mucoadhesion of PU/HPC blends was assessed in the stomach mucosa at pH2.6 at 37 degrees C. Bioadhesion test was performed at pH7.4 at 37 degrees C and revealed a stronger interaction of PU/HPC blends with cellulose membrane than with stomach mucosa. The similar nature of the HPC and cellulose membrane determines additional adhesion forces and implicity high adhesion properties. The HPC component increases the hydrophilicity of the blends as DVS analysis revealed, but also leads to hydrolytic degradation. FTIR spectroscopy analysis was used to evaluate the hydrolytic stability in acid (pH2.6) and slightly alkaline (pH7.4) PBS media and a mechanism of degradation has been proposed.

Investigation of the ability of the oviposition-stimulant lectin from Moringa oleifera seeds (WSMoL) to bind with membrane proteins present in the legs of Aedes aegypti.[Pubmed:32585265]

Int J Biol Macromol. 2020 Jun 22;162:657-662.

The mosquito Aedes aegypti L. is a vector transmitting diseases such as dengue, chikungunya and Zika virus fever. The water-soluble lectin from Moringa oleifera Lam. seeds (WSMoL) is larvicidal, ovicidal and can stimulate oviposition in A. aegypti. This study aimed to investigate whether WSMoL could bind to membrane proteins from A. aegypti legs. Initially, proteins from the legs were extracted using Sodium deoxycholate, digitonin, dodecyl sodium sulfate (SDS) or Triton X-100. The protein concentration was found to be higher in the extract obtained using Triton X-100, which was applied to a WSMoL-Sepharose column. The adsorbed proteins were evaluated using gel filtration chromatography and polyacrylamide gel electrophoresis (PAGE) in presence of SDS. The similarity in the sequences of adsorbed proteins with those available in databases was determined. The proteins adsorbed on the matrix were eluted forming a single peak. Gel filtration chromatography and SDS-PAGE revealed the presence of proteins with molecular masses of approximately 20 kDa and polypeptide bands of 17.0 and 23.7 kDa, respectively. MS/MS analysis indicated similarity between these proteins and ABC carriers, which are expressed in the legs of mosquitos. WSMoL could bind to membrane proteins in the legs of A. aegypti females and induce oviposition through these interactions.

Toward acellular xenogeneic heart valve prostheses: Histological and biomechanical characterization of decellularized and enzymatically deglycosylated porcine pulmonary heart valve matrices.[Pubmed:32557876]

Xenotransplantation. 2020 Jun 18:e12617.

The use of decellularized xenogeneic heart valves might offer a solution to overcome the issue of human valve shortage. The aim of this study was to revise decellularization protocols in combination with enzymatic deglycosylation, in order to reduce the immunogenicity of porcine pulmonary heart valves, in means of cells, carbohydrates, and, primarily, Galalpha1-3Gal (alpha-Gal) epitope removal. In particular, the valves were decellularized with sodium dodecylsulfate/Sodium deoxycholate (SDS/SD), Triton X-100 + SDS (Tx + SDS), or Trypsin + Triton X-100 (Tryp + Tx) followed by enzymatic digestion with PNGaseF, Endoglycosidase H, or O-glycosidase combined with Neuraminidase. Results showed that decellularization alone reduced carbohydrate structures only to a limited extent, and it did not result in an alpha-Gal free scaffold. Nevertheless, decellularization with Tryp + Tx represented the most effective decellularization protocol in means of carbohydrates reduction. Overall, carbohydrates and alpha-Gal removal could strongly be improved by applying PNGaseF, in particular in combination with Tryp + Tx treatment, contrary to Endoglycosidase H and O-glycosidase treatments. Furthermore, decellularization with PNGaseF did not affect biomechanical stability, in comparison with decellularization alone, as shown by burst pressure and uniaxial tensile tests. In conclusion, valves decellularized with Tryp + Tx and PNGaseF resulted in prostheses with potentially reduced immunogenicity and maintained mechanical stability.

[Wenweishu Capsule alleviates gastric mucosal lesion in rats with chronic gastritis by inhibiting NF-kappaB pathway].[Pubmed:32519666]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2020 Apr;36(4):297-303.

Objective To investigate the effect of Wenweishu Capsule on the expression of nuclear factor kappa B (NF-kappaB)-related proteins in chronic gastritis model rats. Methods Wistar rat models of chronic gastritis were constructed by alternant administrations of Sodium deoxycholate, ammonia, alcohol solution and the hunger disorder method. The rats were randomly divided into control group, model group, vatacoenayme group, high-, middle- and low-dose Wenweishu Capsule groups. The control group and model group were treated with normal saline (2 mL/d). The other groups were separately treated with 0.3 g/kg vatacoenayme and 0.76, 0.38, 0.19 g/kg Wenweishu Capsule for 4 weeks. Naked eye observation and HE staining were used to evaluate the pathological changes of gastric tissue. ELISA was performed to measure the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the serum. Immunofluorescence staining was employed to observe the expression of NF-kappaBp65, inhibitor of NF-kappaBalpha (IkappaBalpha) in the gastric tissue. Simple Western was utilized to detect the protein levels of NF-kappaBp65, IkappaBalpha and COX2 in the gastric tissue. Results Compared with the control group, the model group was found with thinner gastric mucosa, disappeared or shallower folds, obviously infiltrated mucosa inflammatory cells, disordered glands, and significantly increased levels of serum inflammatory cytokines and NF-kappaBp65, IkappaBalpha and COX2 proteins in the gastric tissue. Compared with the model group, the vatacoenayme group, high- and middle-dose Wenweishu Capsule groups showed the alleviated gastric cavity signs, improved histopathological changes, reduced levels of TNF-alpha and IL-6 in the serum, and decreased expression of NF-kappaBp65, IkappaBalpha and COX2 proteins in the gastric tissue. Conclusion Wenweishu Capsule can reduce the levels of serum inflammatory factors by inhibiting NF-kappaB pathway in the gastric tissue, so as to alleviate the injury of gastric mucosa in rats with chronic gastritis.