• Journal of Yeungnam Medical Science
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• v.34 no.1
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• pp.115-118
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• 2017

Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia, extremely high serum insulin levels, and high titers of autoantibodies against endogenous insulin, in the absence of exogenous insulin injection. IAS often occurs following exposure to sulfhydryl-containing drugs, including alpha-lipoic acid (ALA). A 30-year-old woman without diabetes visited our outpatient clinic with recurrent hypoglycemia. She had been taken ALA for weight reduction since 3 weeks ago. Further hypoglycemia work up revealed very high insulin levels, C-Peptide levels and positive insulin antibodies. And conventional imaging examinations were negative for insulinoma or other pancreatic tumors. Finally, the diagnosis of Insulin autoimmune syndrome (IAS) was made. Following the cessation of ALA, hypoglycemia improved, with no medication, and the patient experienced no further hypoglycemic attacks over the next month. The use of ALA as a nutritional supplement is increasing. We report a case of IAS associated with ALA in a non-diabetic patient.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.3
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• pp.394-400
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• 2013

A total of 192 broiler chicks were used to evaluate the influence of dietary ${\alpha}$-lipoic acid (ALA) on growth performance, carcass characteristics and meat quality of broiler chickens with the purpose of developing a strategy to prevent the occurrence of pale, soft, and exudative (PSE) meat and to improve the meat quality of broilers. At 22 d of age, birds were allocated to 4 ALA treatments (0, 400, 800, and 1200 ppm). The results showed that dietary ALA significantly decreased average feed intake (AFI), average daily gain (ADG), final live body weight (BW) and carcass weight (p<0.05), while no difference in feed conversion ratio (FCR) was detected among chickens fed with and without ALA. Abdominal fat weight significantly decreased (p<0.05) for broilers fed 800 and 1200 ppm ALA. However when calculated as the percentage of carcass weight there was no significant difference between control and ALA treatments. Meat quality measurements showed that dietary ALA regulated postmortem glycolysis and improved meat quality as evidenced by increased muscle pH and decreased drip loss of meat (p<0.05). Although ALA did not change the tenderness of meat as indicated by meat shear force, dietary ALA decreased collagen content and mRNA expression of COL3A1 gene (p<0.05). In conclusion, the results indicate that dietary ALA may contribute to the improvement of meat quality in broilers.

• Journal of Embryo Transfer
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• v.32 no.3
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• pp.123-130
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• 2017

This study was conducted to investigate the effects of alpha-lipoic acid (aLA) as an antioxidant that decrease the reactive oxygen species (ROS) in bovine embryonic development. Slaughterhouse derived bovine immature oocytes were collected and 4 different concentrations (0, 5, 10 and 20 mM) of aLA was supplemented in bovine in vitro maturation (IVM) medium. After 20 hrs of IVM, maturation rates, levels of ROS and glutathione (GSH), and further embryonic development after parthenogenetic activation (PA) and in vitro fertilization (IVF) was investigated according to aLA concentrations. Maturation rate was significantly higher in 10 mM group than other groups (80.5% vs. 62.9, 73.9, 64.2%; P<0.05). In the levels of ROS and GSH in matured oocytes as an indicator of oocyte quality, significantly better results were shown in 5 and 10 mM groups compared with other 2 groups. After IVM, significantly higher rates of blastocyst formation were shown in 10 mM groups in both of PA (27.9% vs. 18.8, 22.3, 14.2%; P<0.05) and IVF (32.6% vs. 23.9, 27.3, 16.2%; P<0.05) embryos. In addition, significantly more cell total cell number and higher inner cell mass ratio in 10 mM PA and IVP blastocysts showed developmental competence in 10 uM groups. Therefore, based on the entire data from this study, using $10{\mu}M$ of aLA confirmed to be the optimal concentration for bovine oocyte maturation and embryonic development.

• BMB Reports
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• v.52 no.10
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• pp.613-618
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• 2019

Microglial cells are known as the main immune cells in the central nervous system, both regulating its immune response and maintaining its homeostasis. Furthermore, the antioxidant ${\alpha}-lipoic$ acid (LA) is a recognized therapeutic drug for diabetes because it can easily invade the blood-brain barrier. This study investigated the effect of ${\alpha}-LA$ on the inflammatory response in lipopolysaccharide (LPS)-treated BV-2 microglial cells. Our results revealed that ${\alpha}-LA$ significantly attenuated several inflammatory responses in BV-2 microglial cells, including pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and interleukin (IL)-6, and other cytotoxic molecules, such as nitric oxide and reactive oxygen species. In addition, ${\alpha}-LA$ inhibited the LPS-induced phosphorylation of ERK and p38 and its pharmacological properties were facilitated via the inhibition of the nuclear factor kappa B signaling pathway. Moreover, ${\alpha}-LA$ suppressed the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes, multiprotein complexes consisting of NLRP3 and caspase-1, which are involved in the innate immune response. Finally, ${\alpha}-LA$ decreased the genes accountable for the M1 phenotype, $IL-1{\beta}$ and ICAM1, whereas it increased the genes responsible for the M2 phenotype, MRC1 and ARG1. These findings suggest that ${\alpha}-LA$ alleviates the neuroinflammatory response by regulating microglial polarization.

• Analytical Science and Technology
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• v.34 no.4
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• pp.143-152
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• 2021

Capillary electrophoresis (CE) is an effective technique to study chiral recognition because it offers flexibility in adjusting vital factors. Currently, various available cyclodextrins (CDs) can be employed for the chiral separation of numerous analytes. Herein, we investigate the enantioseparation behavior of lipoic acid enantiomers in various types of single and dual CD systems through CE. Additionally, several impacted CE parameters were optimized through the systematic investigation based on the design of experiment (DoE) concept for a single system comprising a heptakis (2,3,6-tri-O-methyl)-β-CD and a dual system containing the combination of the single CD with a sulfated-β-CD. Consequently, absolute enantioresolution was obtained within 15 min on a common standard bare fused-silica capillary (64.5/56 cm in total/effective length, 50/365 ㎛ inner/outer diameter), maintained at 15 ℃ and at an applied voltage of 24 kV. The optimal background electrolyte consisted of 6 mM heptakis (2,3,6-tri-O-methyl)-β-CD dissolved in the solution of 58 mM borate buffer at pH 10. Furthermore, the results of apparent binding constant experiments indicated that the S-enantiomer-heptakis (2,3,6-tri-O-methyl)-β-CD complex exhibited a stronger affinity than its R-enantiomer counterpart. The obtained electrophoretic mobility values could be utilized to interpret the resolution achieved at various CD concentrations and the mobility behavior of the complexes elucidated the migration order of the enantiomers in an electropherogram.

• BMB Reports
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• v.52 no.8
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• pp.508-513
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• 2019

In this study, the anti-inflammatory effects of ${\alpha}-lipoic$ acid (LA) and decursinol (Dec) hybrid compound LA-Dec were evaluated and compared with its prodrugs, LA and Dec. LA-Dec dose-dependently inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) generation in BV2 mouse microglial cells. On the other hand, no or mild inhibitory effect was shown by the Dec and LA, respectively. LA-Dec demonstrated dose-dependent protection from activation-induced cell death in BV2 cells. LA-Dec, but not LA or Dec individually, inhibited LPS-induced increased expressions of induced NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in a dose-dependent manner in both BV2 and mouse macrophage, RAW264.7 cells. Furthermore, LA-Dec inhibited LPS-induced expressions of iNOS, COX-2, interleukin-6, tumor necrosis $factor-{\alpha}$, and $interleukin-1{\beta}$ mRNA in BV2 cells, whereas the same concentration of LA or Dec was ineffective. Signaling studies demonstrated that LA-Dec inhibited LPS-activated signal transducer and activator of transcription 3 and protein kinase B activation, but not nuclear factor-kappa B or mitogen-activated protein kinase signaling. The data implicate LA-Dec hybrid compound as a potential therapeutic agent for inflammatory diseases of the peripheral and central nervous systems.

• International Journal of Oral Biology
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• v.46 no.1
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• pp.15-22
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• 2021

Alpha-lipoic acid (ALA) is a naturally occurring antioxidant and has been previously used to treat diabetes and cardiovascular disease. However, the autophagy effects of ALA against oxidative stress-induced dopaminergic neuronal cell injury remain unclear. The aim of this study was to investigate the role of ALA in autophagy and apoptosis against oxidative stress in the SH-SY5Y human dopaminergic neuronal cell line. We examined SH-SY5Y phenotypes using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay (cell viability/proliferation), 4′,6-diamidino-2-phenylindole dihydrochloride nuclear staining, Live/Dead cell assay, cellular reactive oxygen species (ROS) assay, immunoblotting, and immunocytochemistry. Our data showed ALA attenuated hydrogen peroxide (H2O2)-induced ROS generation and cell death. ALA effectively suppressed Bax up-regulation and Bcl-2 and Bcl-xL down-regulation. Furthermore, ALA increased the expression of the antioxidant enzyme, heme oxygenase-1. Moreover, the expression of Beclin-1 and LC-3 autophagy biomarkers was decreased by ALA in our cell model. Combined, these data suggest ALA protects human dopaminergic neuronal cells against H2O2-induced cell injury by inhibiting autophagy and apoptosis.

• Polymer(Korea)
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• v.34 no.2
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• pp.178-183
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• 2010

Medical metal stents inserted to patients with a cardiovascular disease associated with coronary artery system have relatively increased the survival rate. The development of new stents is, however, urgently required due to restenosis and late thrombosis generated in metal stents. To solve these problems, the biodegradable polymers such as poly(lactide-co-glycolide) (PLGA), poly(L-lactide)(PLLA), and poly ($\varepsilon$-caprolactone)(PCL) were mixed with alpha lipoic acid (ALA), which is well known to inhibit the proliferation of neointimal hyperplasia. Subsequently, the ALA-loaded polymers were coated on stainless steel by electrospray. The drug-eluting behaviors from the coated polymers were investigated according to kinds and concentrations of polymers, spray rates, and kinds of solvents. The drug-eluting rate from PCL with the lowest glass transition temperature was the fastest among three polymers and followed by PLGA and PLLA. The surface roughness increased as the spray rate was increased and also the drug-eluting rate was affected by kinds of solvents with different boiling point. It is expected that drug-eluting stent (DES) coated with ALA-loaded polymers can be applied practically for clinical applications by controlling the behavior of drug release.

• Bulletin of the Korean Chemical Society
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• v.35 no.6
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• pp.1681-1686
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• 2014

A series of hybrid molecules between (${\alpha}$)-lipoic acid (ALA) and 4-amino-1-benzyl piperidines were synthesized and their in vitro cholinesterase (acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)) inhibitory activities were evaluated. Even though the parent compounds did not exhibit any inhibitory activity against cholinesterase (ChE) with the exception of compound 14 ($IC_{50}=255.26{\pm}4.41$ against BuChE), all hybrid molecules demonstrated BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, compound 17 was shown to be an effective inhibitor against both AChE ($IC_{50}=1.75{\pm}0.30{\mu}M$) and BuChE ($IC_{50}=5.61{\pm}1.25{\mu}M$) comparable to galantamine ($IC_{50}=1.7{\pm}0.9{\mu}M$ against AChE and $IC_{50}=9.4{\pm}2.5{\mu}M$ against BuChE). Inhibition kinetic studies using compound 17 indicated a mixed inhibition type for AChE and a noncompetitive inhibition type for BuChE. Its binding affinity ($K_i$) values to AChE and BuChE were $3.8{\pm}0.005{\mu}M$ and $7.0{\pm}0.04{\mu}M$, respectively.

• Journal of Sensor Science and Technology
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• v.23 no.5
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• pp.295-298
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• 2014

A novel approach to fabricating high-performance glucose sensors is reported, which is based on the process of self-assembled monolayers (SAMs). In this study, we have particularly used ${\alpha}$-lipoic acid (LA) SAMs for the glucose sensors. To our best knowledge, this study is the first one to use LA as SAMs for this purpose. N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) were deliberately attached at the same time on the LA SAM. Then, glucose oxidase ($GO_X$) and horseradish peroxidase (HRP) were sequentially immobilized. Thus, the HRP/$GO_X$/NHS-EDC/LA-SAM/Au/Cr/glass working electrode was developed. The glucose-sensing capability of the fabricated sensor was systematically measured by the use of cyclic voltammetry in the range of 1-30 mM glucose in phosphate-buffered saline. The result showed a good sensitivity, that is, as high as $27.5{\mu}A/(mM{\cdot}cm^2)$. This result conspicuously demonstrates that LA can be one of promising substances for use as SAMs for accurately monitoring trace levels of glucose concentration in human blood.