And Α-lipoic Acid Research Articles

Protective Action of Curcumin and Alpha-lipoic Acid, Against Experimental Ultraviolet-A/B Induced Dermal-injury in Rats.

The objective of this study was to examine the therapeutic efficacy of curcumin (CUR) and α-lipoic acid (ALA) in mitigating UV-A and UV-B-induced damage (UVAB) in rat dorsal skin. This was achieved through the utilisation of immunohistochemical (TUNEL), biochemical and stereological techniques. The rats in the UVAB, UVAB + CUR, and UVAB + ALA groups were subjected to UVAB irradiation for a period of two hours per day over the course of one month. The UVAB + CUR and UVAB + ALA groups were administered 100 mg/kg/day of curcumin and 100 mg/kg/day of α-lipoic acid via gavage 30 min prior to UVAB irradiation. The CUR group was administered 100 mg/kg/day of curcumin via gavage, while the ALA group received the same dose of α-lipoic acid. A significant change in the volume ratio of the dorsal skin epidermis and dermis was observed in the stereological findings of the rats in the UVAB group. These changes exhibited a favourable progression as a consequence of the CUR and ALA applications. In the UVAB group, TOS and OSI were significantly elevated as a consequence of the rise in oxidative stress. Conversely, the treatment groups demonstrated a notable reduction in TOS and OSI levels. The study also revealed a substantial increase in the number of apoptotic cells within the UVAB group. However, the treatment groups exhibited a significant decline in apoptotic cells. In conclusion, the findings suggest that CUR and ALA possess a protective effect against UVAB-induced skin damage.

Вторичные мессенджеры инсулина при синдроме поликистозных яичников и методы его патогенетической коррекции

The study of new mechanisms of insulin resistance (IR) formation is a prerequisite for the development of new pathogenetically-oriented therapies of polycystic ovary syndrome (PCOS) and the treatment of associated disorders of carbohydrate and fat metabolism. Important regulators of insulin signaling are its secondary messengers, namely myo-inositol (MI), D-chiro inositol (DCI), and α-lipoic acid (ALA), which mediate various effects of insulin. Consequently, MI induces cellular glucose uptake and enhances glycolysis, whereas DCI stimulates glycogenesis and regulates energy metabolism. The physiologic MI/DCI ratio for oocytes is crucial for oogenesis, steroidogenesis, and the regulation of the menstrual cycle. ALA provides insulinomimetic effects through the induction of glucose translocation into cells, antioxidant and anti-inflammatory effects on pancreatic cells, and the suppression of lipolysis and the reduction of triglyceride levels. A wealth of evidence from large-scale studies, meta-analyses, and systematic reviews has demonstrated the crucial role of MI, DCI, and ALA in the treatment of PCOS. A multitude of studies, including those conducted by the authors, have demonstrated that the administration of these substances results in a reduction in HOMA, levels of glucose, insulin, triglycerides, low-density lipoproteins, and body mass index. This, in turn, has been shown to restore ovulation and the menstrual cycle in women with PCOS, as well as to reduce the risk of cardiometabolic diseases, including diabetes and nonalcoholic fatty liver disease KEYWORDS: polycystic ovary syndrome, inositol, myo-inositol, D-chiro inositol, alpha-lipoic acid, insulin resistance, fat metabolism, nonalcoholic fatty liver disease FOR CITATION: Ivanov I.A., Tabeeva G.I., Smetnik A.A. Secondary messengers of insulin in polycystic ovary syndrome and its pathogenically- oriented treatment. Russian Journal of Woman and Child Health. 2024;7(2):135–143 (in Russ.). DOI: 10.32364/2618-8430-2024-7-2-8.

Evaluation of the regulatory effect of carnosine and alpha-lipoic acid on the cytokine profile of the cerebral cortex of Wistar rats under induced obesity

BACKGROUND:The model of obesity under experimental conditions is reproduced by using high-calorie diets in animals. It has been established that metabolic disorders cause meta-inflammation not only in peripheral organs and tissues, but also in brain structures. The search for effective neuroprotective antioxidants to suppress inflammatory processes in the cerebral cortex in obesity is an urgent task due to the widespread prevalence of this disease.AIM: to evaluate the effect of minor biologically active substances — carnosine (CAR) and α-lipoic acid (ALA) on the cytokine profile of the frontal cortex of the left hemisphere of the brain in Wistar male rats with obesity induced by a high-calorie choline-deficient diet.MATERIALS AND METHODS:The studies were carried out on male Wistar rats with an initial body weight of 150±10 g. The animals were randomized by body weight into 5 groups. For 8 weeks, rats of the 1st (control) group received a complete modified diet of AIN93M; rats of the 2nd group consumed a high-calorie choline-deficient diet (HCHDR), the fat content of which was 45%, fructose — 20% of the energy value of the diet; rats of the 3rd group received HCHDR with the addition of CAR at a dose of 75 mg per 1 kg of body weight; rats of the 4th group received HCHDR with the addition of ALA at a dose of 75 mg per 1 kg of body weight; rats of the 5th group received HCHDR with the addition of the CAR + ALA complex in a total dose of 150 mg per 1 kg of body weight. Animals were removed from the experiment by decapitation under ether anesthesia. The levels of triglycerides (Tg) and free fatty acids (FFA) in blood plasma (mmol) were determined on a biochemical analyzer (Konelab 20i, Thermo Clinical Labsystems Oy, Finland). Content of cytokines and chemokines (pg/ml): GM-CSF, IL-10, IL-17A, IL-12p40, IL-12p70, IL-1α, IL-2, IL-4, IL-5, IFN-γ, MCP-1, M-CSF, MIP-1α, MIP-2, MIP-3α, RANTES, and TNF-α in cerebral cortex lysates were determined by multiplex immunoassay using a Luminex 200 analyzer (Luminex Corporation, USA). To assess the relationship between the level of cytokines in blood plasma and changes in their concentrations under the influence of HCCDR in lysates of the cortex of the frontal lobe of the left hemisphere of the brain, the ratio was calculated: the level of cytokines pg/ml in blood plasma [1]/the content of cytokines pg/ml in lysates (pl/ lys) for each sample.RESULTS: On the model of obesity in rats, the presence of an inflammatory process in the cerebral cortex was established, as evidenced by an increase in the content of pro-inflammatory factors: IL-2, M-CSF, MIP-1α and RANTES and a decrease in the content of immunoregulatory cytokines of varying severity: IL-10, IL17A, IL-12p40, IL-12p70, TNF-a, MIP-2 and MIP-3α in group 2 rats. (HCHDR) compared with the control group. Enrichment of HCHDR with biologically active substances: CAR, ALA or their complex, ensured the normalization of lipid metabolism, as evidenced by the decrease in the ratio of circulating Tg to FFA in the blood serum of rats to control values: 1st gr. (control) — 1,04±0.23; 2nd gr. (HCHDR) — 1,64±0.63; 3rd gr. (CAR) — 0,98±0.31; 4th gr. (ALA) — 0,86±0.31; 5th gr. (CAR+ALA) — 1,02±0.38. Enrichment of HCHDR with CAR, ALA or their complex led to a decrease in the content of pro-inflammatory and apoptosis-regulating cytokines and chemokines in the cortex of the frontal lobe of the rat brain: IL-1α, IL-2, IL-17A, M-CSF, MCP-1, MIP3α and RANTES, along with an increase in the level of the anti-inflammatory cytokine IL-10, which indicates the suppression of the inflammatory process induced by the consumption of HCHDR in rats.CONCLUSION:The data obtained indicate the prospect of using CAR and ALA or their complex as neuroprotective antioxidants to reduce the inflammatory process in brain structures in obesity.

Diverse impact of N-acetylcysteine or alpha-lipoic acid supplementation during high-fat diet regime on fatty acid transporters in visceral and subcutaneous adipose tissue

PurposeAdipose tissue's (AT) structural changes accompanying obesity may alter lipid transport protein expression and, thus, the fatty acids (FAs) transport and lipid balance of the body. Metabolic abnormalities within AT contribute to the elevated production of reactive oxygen species and increased oxidative/nitrosative stress. Although compounds such as N-acetylcysteine (NAC) and α-lipoic acid (ALA), which restore redox homeostasis, may improve lipid metabolism in AT, the mechanism of action of these antioxidants on lipid metabolism in AT is still unknown. This study aimed to examine the impact of NAC and ALA on the level and FA composition of the lipid fractions, and the expression of FA transporters in the visceral and subcutaneous AT of high-fat diet-fed rats. Materials and methodsMale Wistar rats were randomly divided into four groups. The mRNA levels and protein expression of FA transporters were assessed using real-time PCR and Western Blot analyses. The collected samples were subjected to histological evaluation. The level of lipids (FFA, DAG, and TAG) was measured using gas-liquid chromatography. ResultsWe found that antioxidants affect FA transporter expressions at both the transcript and protein levels, and, therefore, they promote changes in AT's lipid pools. One of the most remarkable findings of our research is that different antioxidant molecules may have a varying impact on AT phenotype. ConclusionNAC and ALA exert different influences on AT, which is reflected in histopathological images, FA transport proteins expression patterns, or even the lipid storage capacity of adipocytes.

Simultaneous detection of dopamine, uric acid and α-lipoic acid using nickel hydroxide nanosheets

In this work, nickel hydroxide nanosheets were synthesised by a simple and facile method and were used for simultaneous detection of dopamine, uric acid and α-lipoic acid. The synthesis was based on the co-precipitation method involving sodium borohydride and nickel nitrate. The nanosheets were characterised by various microscopic and spectroscopic methods. Due to their 2D structure, nickel hydroxide nanosheets has several exposed active sites making them electrochemically active. Electrochemical properties were analysed using cyclic voltammetry and differential pulse voltammetry in 0.1 M PBS (pH 7.4). The electrochemical sensor made using the nanosheets could detect dopamine (DA), uric acid (UA) and α-lipoic acid (ALA) in PBS buffer, making them an excellent sensor. The simultaneous detection of DA, UA and ALA, also can be performed. The calculated value of the limit of detection (LOD) for DA, UA and ALA were 1.32, 1.701 and 2.66 µM, respectively. The present electrochemical sensor exhibited good stability, repeatability and high selectivity.

Roles of Exogenous α-Lipoic Acid and Cysteine in Mitigation of Drought Stress and Restoration of Grain Quality in Wheat.

Cysteine (Cys) and α-lipoic acid (ALA) are naturally occurring antioxidants (sulfur-containing compounds) that can protect plants against a wide spectrum of environmental stresses. However, up to now, there are no conclusive data on their integrative roles in mitigation of drought stress in wheat plants. Here, we studied the influence of ALA at 0.02 mM (grain dipping pre-cultivation treatment) and Cys (25 and 50 ppm as a foliar application) under well watered and deficit irrigation (100% and 70% of recommended dose). The results showed that deficit irrigation markedly caused obvious cellular oxidative damage as indicated by elevating the malondialdehyde (MDA) and hydrogen peroxide content (H2O2). Moreover, water stressed plants exhibited multiple changes in physiological metabolism, which affected the quantitative and qualitative variables of grain yield. The enzymatic antioxidants, including superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT) and peroxidase (POX) were improved by Cys application. SOD and APX had the same response when treated with ALA, but CAT and POX did not. Moreover, both studied molecules stimulated chlorophyll (Chl) and osmolytes’ biosynthesis. In contrast, the Chl a/b ratio was decreased, while flavonoids were not affected by either of the examined molecules. Interestingly, all above-mentioned changes were associated with an improvement in the scavenging capacity of reactive oxygen species (ROS), leaf relative water content (RWC), grain number, total grain yield, weight of 1000 kernels, gluten index, falling number, and alveographic parameters (P, W, and P/L values). Furthermore, heatmap plot analysis revealed several significant correlations between different studied parameters, which may explore the importance of applied Cys and ALA as effective compounds in wheat cultivation under water deficit conditions.

Antioxidants Supplementation Reduces Ceramide Synthesis Improving the Cardiac Insulin Transduction Pathway in a Rodent Model of Obesity.

Obesity-related disruption in lipid metabolism contributes to cardiovascular dysfunction. Despite numerous studies on lipid metabolism in the left ventricle, there is no data describing the influence of n-acetylcysteine (NAC) and α-lipoic acid (ALA), as glutathione precursors, on sphingolipid metabolism, and insulin resistance (IR) occurrence. The aim of our experiment was to evaluate the influence of chronic antioxidants administration on myocardial sphingolipid state and intracellular insulin signaling as a potential therapeutic strategy for obesity-related cardiovascular IR. The experiment was conducted on male Wistar rats fed a standard rodent chow or a high-fat diet with intragastric administration of NAC or ALA for eight weeks. Cardiac and plasma sphingolipid species were assessed by high-performance liquid chromatography (HPLC). The proteins expressed from sphingolipid and insulin signaling pathways were determined by Western blot. Antioxidant supplementation markedly reduced ceramide accumulation by lowering the expression of selected proteins from the sphingolipid pathway and simultaneously increased the myocardial sphingosine-1-phosphate level. Moreover, NAC and ALA augmented the expression of GLUT4 and the phosphorylation state of Akt (Ser473) and GSK3β (Ser9), which improved the intracellular insulin transduction pathway. Based on our results, we may postulate that NAC and ALA have a beneficial influence on the cardiac ceramidose under IR conditions.

Bone marrow mononuclear cells boosts anti-cytogentical aberration effect of N-acetylcysteine and α-lipoic acid in rat’s liver and bone marrow: implication of oxidative and inflammatory pathways

This study investigates the hepatoprotective effect of bone marrow mononuclear cells (BM-MNCs) transplantation, N-acetylcysteine (NAC) and α-lipoic acid (ALA). Rats were administrated carbon tetrachloride (CCl4) (1 mg/kg, i.p.) twice/week for 8 weeks for the induction of hepatotoxicity. 7 groups of rats were used as follows: Normal control, CCl4, CCl4 co-administered with BM-MNCs (1 × 106 in 0.1 ml PBS, i.v.), or NAC (300 mg/kg, p.o) or ALA (100 mg/kg, p.o) single or combination. Liver function was tested by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin as well as interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (Gpx), superoxide dismutase (SOD) and catalase (CAT) activities in liver homogenates. Besides that, estimation of DNA damage was performed. In addition to Micronucleus test and histopathological investigation. CCl4 treated rats showed elevation in ALT, AST, TNF-α, IL-6 and MDA accompanied by reduction in ALB, IL-10, SOD, CAT, GPx and TAC and increased the number of DNA breaks in liver tissue, showed many micronucleated polychromatic erythrocytes (MnPCEs) in bone marrow. NAC, ALA, BM-MNCs and their combination caused a reduction of ALT, AST, while, increase albumin, CAT, TAC, GPx, SOD as compared to CCl4 treated groups. Also decrease in MDA, IL-6 and TNF-α concurrently with an increase in IL-10. Moreover, BM-MNCs, NAC, ALA, and their combination decreased DNA tail %, and the count of MnPCEs. BM-MNCs combination with NAC or ALA exerted significant antioxidant, anti-inflammatory and anti-cytogenetical aberrations effect compared to each of them alone. Highlights CCl4 elevated ALT, AST, TNF-α, IL-6 and MDA CCl4 reduced ALB, IL-10, SOD, CAT, GPx and TAC CCl4 increased the number of DNA breaks in liver NAC, ALA and BM-MNCs reduced ALT, AST, while, increase albumin, CAT, TAC, GPx, SOD NAC, ALA and BM-MNCs decreased in MDA, IL-6 and TNF-α and increased IL-10

Astragaloside IV Inhibits Mitochondrial-Dependent Apoptosis of the Dorsal Root Ganglion in Diabetic Peripheral Neuropathy Rats Through Modulation of the SIRT1/p53 Signaling Pathway.

PurposeTo investigate the effect of astragaloside IV (AS-IV) on mitochondrial-dependent apoptosis in the dorsal root ganglion of diabetic peripheral neuropathy (DPN) rats through the SIRT1/p53 pathway.MethodsDiabetic rat model was induced by high-carbohydrate/high-fat diet and intraperitoneal injection of STZ. Diabetic rats were divided into three groups (n =16 per group): DPN group, AS-IV group (60mg/kg/d) and α-lipoic acid (ALA) group (60mg/kg/d). Weight and blood glucose levels were monitored every 4 weeks for 12 weeks. DPN was evaluated using the Von Frey Filaments Test and nerve conduction velocity. The dorsal root ganglia of rats were isolated and the pathological changes of mitochondria were observed by electron microscopy. The activity of mitochondrial electron transport chain complex, mitochondrial membrane potential, malonaldehyde (MDA) and glutathione (GSH) levels were measured. Neural apoptosis was detected using the Terminal Deoxynucleotidyl Nick-End Labeling (TUNEL) assay kit. The cleaved caspase-3, major proteins in the SIRT1/p53 pathway, including SIRT1, acetyl p53, Drp1, BAX, and BCL-2, were detected using immunohistochemistry and Western blot. Gene expression of major proteins in the SIRT1/p53 pathway was also detected.ResultsAfter 12 weeks of treatment, AS-IV and ALA did not significantly affect body weight or fasting glucose levels, but reduced mechanical abnormal pain in DPN and improved nerve conduction velocity. AS-IV and ALA increased the level of GSH and decreased the level of MDA. Both AS-IV and ALA can reduce mitochondrial damage, improve mitochondrial electron transport chain complex activity and mitochondrial membrane potential, and reduce the percentages of positive cells with DNA fragmentation and the expression of cleaved caspase-3 protein. AS-IV and ALA up-regulated the expression of SIRT1 and down-regulated the expression of acetyl-p53, Drp1 and the ratio of BAX to BCL-2. Changes in gene expression were similar.ConclusionAS-IV can reduce the occurrence of mitochondrial-dependent apoptosis by regulating the SIRT1/p53 pathway. It has a similar therapeutic effect as ALA and is therefore a promising drug for the potential treatment of DPN.

Creatine and α-lipoic acid improved depressive behavior induced by interferon-α in mice: Malondialdehyde level remained unchanged

Objective: Interferon-alpha (IFNa) is a cytokine with various biological roles but it may induce psychological adverse effects. Introducing alternative medicine is essential to prevent this side effect. This study was performed to determine the antidepressant effects of creatine (Crt) and α-lipoic acid (ALA). Materials and Methods: Female albino mice (6–8 weeks old) were used. IFNa (16×105 IU/kg/day, SC), Crt (5 and 10 mg/kg, gavage feeding tube), and ALA (20 and 40 mg/kg, IP) were administered for 6 days. After the locomotor test, behavioral parameters of depression, including immobility during the forced swimming test (FST), and finally serum malondialdehyde (MDA) were measured as factors for oxidative stress. Results: There was not important difference regarding the locomotor test. Crt 5 mg/kg and ALA 40 mg/kg when administered alone reduced the immobility time during FST when compared with the control groups (75±15 and 82±16 s, respectively, P < 0.05). Crt 5 mg/kg and IFN co-administration reduced the immobility time to 108±23 s, which was lower than that of the IFNa alone group (156±8 s, P < 0.05). Administrating ALA 40 mg/kg and IFNa together showed same results (95±11 s vs. IFNa alone group, P < 0.01). The results of measuring MDA did not show noticeable difference. Conclusion: In general, improvement of behavioral parameters in mice treated with Crt and ALA indicates a clear effect of these two compounds in modulating mood and depressive behaviors. Although MDA level differences were not observed, Crt and ALA modulation in the neurotransmitter system may be involved in their antidepressant effects.

Phloroglucinol Strengthens the Antioxidant Barrier and Reduces Oxidative/Nitrosative Stress in Nonalcoholic Fatty Liver Disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) is one of the most commonly occurring diseases within western dietary patterns. Usually untreated, it may lead to type 2 diabetes mellitus (T2DM), steatohepatitis (NASH), and hepatocellular carcinoma (HCC). Besides its severe aftermath, up to now, there is no known therapeutic approach to this disease in everyday clinical practice. Most NAFLD patients are encouraged to do physical activities or diet change and remain without pharmacological treatment. In this study, we present phloroglucinol (PHG) as a novel and promising compound in NAFLD treatment. PHG significantly increased the level of enzymatic and nonenzymatic antioxidants both in palmitate and hydrogen peroxide-induced oxidative stress models. Strengthened antioxidative defense reduced the oxidative/nitrosative damage to cell proteins, lipids, and carbohydrates. Furthermore, PHG treatment reduced hepatic steatosis; lowered inflammatory markers, such as NF-κB or HIF-1α; and inhibited cell apoptosis. Moreover, PHG had a more comprehensive effect than other commonly used antioxidants: N-acetylcysteine (NAC) and α-lipoic acid (ALA), suggesting its clinical usability. Therefore, our paper supports the benefits of natural compounds as a therapeutical approach to NAFLD.

Randomized clinical trial of combined therapy with oral α-lipoic acid and NB-UVB for nonsegmental stable vitiligo.

Vitiligo is associated with oxidant stress and α-lipoic acid (ALA) is an antioxidative agent. To evaluate the efficacy and safety of oral ALA in combination with NB-UVB phototherapy on nonsegmental stable vitiligo. The prospective, multi-center, parallel controlled, double-blind randomized clinical trial was conducted from 2012 to 2014, in seven comprehensive tertiary hospitals in China. The patients were randomized into oral ALA group or placebo group at a dose of 300 mg daily for 6 months. All of them received NB-UVB phototherapy three times weekly. The repigmentation rate was evaluated by 4-point grading scale of improvement: >98%, 50-98%, 10-49%, <10%. A total of 133 patients were enrolled in the study, including 72 cases in treatment group and 61 cases in control group. In treatment group, 2.04% (1/49) patients achieved ≥50% improvement at 1-month after enrollment (M1), and the percentage of patients increased to 8.51% (4/47), 14.0% (6/43), and 37.8% (14/37) at M2, M3, and M6, respectively. In control group, the percentages were similar at all timepoints. No significant difference was seen between the two groups (P > .05). For elder patients, younger patients, male or female, no significant differences were found between treatment group and control group at all timepoints. ALA did not show additional benefit to NB-UVB therapy in the treatment of nonsegmental stable vitiligo. More studies should be done to identify other protocols of ALA or other types of antioxidants for stable vitiligo.

NGF receptors and PI3K/AKT pathway involved in glucose fluctuation-induced damage to neurons and \u03b1-lipoic acid treatment

BackgroundGlucose fluctuation promotes neuronal apoptosis, which plays a central role in diabetic encephalopathy (DE). Nerve growth factor (NGF), and its interaction with high-affinity (TrkA) and low-affinity (p75NTR) receptors, are involved in neuronal survival. NGF/TrkA contributes to the activation of the PI3K/AKT pathway, which is beneficial for neuronal survival, and α-Lipoic acid (ALA) exerts clinically favorable neuroprotective effects in the periphery. Whether NGF receptors and the PI3K/AKT pathway are involved in glucose fluctuation-induced neuronal damage, as well as the potential molecular mechanism of ALA in protecting glucose fluctuation-induced neuronal damage, remain unclear.ResultsThe results indicated that constant high glucose (CHG) and intermittent high glucose (IHG) significantly increased the expression of Bax and caspase-3, and decreased the expression of TrkA/p75NTR and p-AKT/AKT, while ALA stimulation reversed the above proteins in PC12 cells. IHG stimulates apoptosis more effectively than CHG in PC12 cells, which is related to the PI3K/AKT pathway but not to the TrkA/p75NTR. Furthermore, neuronal apoptosis induced by IHG was aggravated by the TrkA inhibitor K252a or the PI3K/AKT inhibitor LY294002, but this effect was alleviated by the p75NTR inhibitor TAT-pep5.ConclusionGlucose fluctuation induced cell apoptosis by regulating the TrkA/p75NTR and PI3K/AKT pathway, meanwhile ALA exhibited neuroprotective effects in response to IHG and CHG. These observations indicated that the PI3K/AKT pathway and the balance of TrkA/p75NTR are likely to serve as potential therapeutic targets for DE. In addition, ALA could be a possible therapeutic drug for DE.

Assessment of diets containing curcumin, epigallocatechin-3-gallate, docosahexaenoic acid and α-lipoic acid on amyloid load and inflammation in a male transgenic mouse model of Alzheimer's disease: Are combinations more effective?

Increasingly, evidence is accumulating pointing at a protective role of a healthy diet at decreasing the risk of Alzheimer's disease. To test the effectiveness of nutritional components, the following food-derived compounds: curcumin alone (curcumin), curcumin combined with (−)epigallocatechin-3-gallate (EGCG), docosahexaenoic acid (DHA) and α-lipoic acid (ALA) (curcumin + EDA), or a combination of EGCG, DHA and ALA (EDA) were assessed in male Tg2576 transgenic mice on amyloid plaque load, amyloid levels (Aβ40/Aβ42, but not oligomers due to tissue limitations), microglial activation and memory using the contextual and cued fear conditioning test. The combination diet EDA, resulted in the strongest reduction of amyloid plaque load in both the cortical (p < .0001) and hippocampal (p < .0001) areas of the Tg2576 mouse brain, along with lower Aβ40/Aβ42 levels in the frontal cortex (p = .000129 and p = .000039, respectively) and Aβ42 levels in the temporal lobe (p = .000082). A curcumin only diet was shown to lower amyloid plaque load (p = .028), but when combined with EGCG, DHA and ALA did not result in further decreases in amyloid plaque load. The EDA combination group showed the most prominent decrease in microglial activation (number of microglia around plaques: p < .05 and p < .0001, respectively, for the cortex and hippocampus). Analysing the hippocampal associated contextual fear conditioning revealed that both the curcumin+EDA (p < .0001) and EDA groups (p = .001) spent increased time on freezing compared to the control group. In addition, the curcumin+EDA group showed a significant increase in time spent freezing compared with the curcumin only group. In the amygdala associated cued test, all mice demonstrated the ability to associate the conditioned stimulus with the unconditioned stimulus as evidenced by a significant increase in freezing behaviour in response to the presentation of the cue (p < .0001). Post-hoc analysis showed that only curcumin+EDA (p < .0001) and EDA groups (p < .0001) developed a significant increase in freezing during the cue presentation. The results from this study show that the combination of EGCG, DHA and ALA (EDA) appeared to have the most potent anti-inflammatory and neuroprotective effect. Our results also demonstrate that interactions between nutraceutical products might result in counterproductive outcomes, highlighting the fact that manufacturers of nutraceuticals containing multiple compounds should be careful not to claim additive or synergistic effects of their combination products in vivo without having tested it in animal models and/or human clinical trials.

Lack of preventive effect of maternal exposure to α-glycosyl isoquercitrin and α-lipoic acid on developmental hypothyroidism-induced aberrations of hippocampal neurogenesis in rat offspring.

Hypothyroidism during the developmental stage induces disruption of hippocampal neurogenesis in later life, as well as inducing oxidative stress in the brain. The present study investigated the preventive effect of co-exposure to an antioxidant on disruptive neurogenesis induced by developmental exposure to anti-thyroid agent in rats. For this purpose, we used two antioxidants, α-glycosyl isoquercitrin (AGIQ) and α-lipoic acid (ALA). Mated female Sprague Dawley rats were either untreated (control) or treated with 12 ppm 6-propyl-2-thiouracil (PTU), an anti-thyroid agent, in drinking water from gestational day 6 to postnatal day (PND) 21, the latter group being subjected to feeding basal diet alone or diet containing AGIQ at 5,000 ppm or ALA at 2,000 ppm during PTU exposure. On PND 21, PTU-exposed offspring showed reductions in a broad range of granule cell lineage subpopulations and a change in the number of GABAergic interneuron subpopulations. Co-exposure of AGIQ or ALA with PTU altered the transcript levels of many genes across multiple functions, suggestive of enhancement of synaptic plasticity and neurogenesis. Nevertheless, immunohistochemical results did not support these changes. PTU exposure and co-exposure of AGIQ or ALA with PTU did not alter the hippocampal lipid peroxidation level. The obtained results suggest a possibility that thyroid hormone depletion itself primarily disrupts neurogenesis and that oxidative stress may not be involved in the disruption during development. Transcript expression changes of many genes caused by antioxidants may be the result of neuroprotective actions of antioxidants rather than their antioxidant activity. However, no preventive effect on neurogenesis suggested impairment of protein synthesis via an effect on mRNA translation due to hypothyroidism.

Low-cost and disposable sensors for the simultaneous determination of coenzyme Q10 and α-lipoic acid using manganese (IV) oxide-modified screen-printed graphene electrodes

In this work, for the first time, manganese (IV) oxide-modified screen-printed graphene electrodes (MnO2/SPGEs) were developed for the simultaneous electrochemical detection of coenzyme Q10 (CoQ10) and α-lipoic acid (ALA). This sensor exhibits attractive benefits such as simplicity, low production costs, and disposability. Cyclic voltammetry (CV) was used to characterize the electrochemical behavior of the analyte and investigate the capacitance and electroactive surface area of the unmodified and modified electrode surfaces. The electrochemical behavior of CoQ10 and ALA on MnO2/SPGEs was also discussed. Additionally, square wave anodic stripping voltammetry (SWASV) was used for the quantitative determination of CoQ10 and ALA. Under optimal conditions, the obtained signals are linear in the concentration range from 2.0 to 75.0 μg mL−1 for CoQ10 and 0.3–25.0 μg mL−1 for ALA. The low limits of detection (LODs) were found to be 0.56 μg mL−1 and 0.088 μg mL−1 for CoQ10 and ALA, respectively. Moreover, we demonstrated the utility and applicability of the MnO2/SPGE sensor through simultaneous measurements of CoQ10 and ALA in dietary supplements. The sensor provides high accuracy measurements, exhibiting its high potential for practical applications.

Curative role of lactulose, L-carnitine, alpha-lipoic acid and combination of L-carnitine and alpha-lipoic acid in a rat model of acute hepatic encephalopathy: Biochemical observations

Purpose: To determine whether a combination L-carnitine and α-lipoic acid (ALA) can alleviate the toxic effects of thioacetamide (TAA) via their potent antioxidant and free radical-scavenging activities. Methods: Rats were injected with TAA for 3 days to induce acute hepatic failure. TAA induced rats were treated with each of lactulose, L-carnitine and ALA alone and a combination of L-carnitine and ALA for 3 months. Thereafter, biochemical indices, ammonia levels, oxidative stress markers, and the levels of inflammatory markers were assessed in serum, liver and brain. Results: A significant improvement was observed after 3 months of antioxidants treatment. Lactulose, L-carnitine and ALA significantly decreased serum concentrations of alanine transaminase (ALT), aspartate aminotransaminase (AST) and level of total bilirubin while both levels of total protein (TP) and albumin (ALB) were significantly increased ( p < 0.05 ) compared to TAA group. In addition, each of antioxidants alone significantly decreased ammonia (NH3) concentrations of serum, liver and brain in TAA-induced rats. Treatment with antioxidants for 3 months significantly ( p < 0.05) decreased Malondialdehyde (MDA) and nitric oxide (NO) while antioxidant enzyme activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were significantly increased ( p < 0.05) in liver and brain tissues. The expressions of serum tumor necrosis factor-α (TNF-α) and soluble protein (S100-β) were significantly ( p < 0.05) down-regulated in TAA-induced rats. Conclusion: L-carnitine in combination with ALA can mitigate HE induced experimentally in rats. The protective efficacy of L-carnitine in combination with ALA in HE can be attributed to suppression of oxidative stress, ammonia concentration and the levels of inflammatory markers. Thus, it may have the potential to be used to treat liver cirrhosis in clinical settings. Keywords: Lactulose, L-carnitine, α-Lipoic acid, Hepatic encephalopathy, Thioacetamide, Oxidative stress, Cirrhosis, Acute liver injury

Anti-inflammatory effects of the selective phosphodiesterase 3 inhibitor, cilostazol, and antioxidants, enzymatically-modified isoquercitrin and α-lipoic acid, reduce dextran sulphate sodium-induced colorectal mucosal injury in mice

Developing effective treatments and preventing inflammatory bowel disease (IBD) are urgent challenges in improving patients’ health. It has been suggested that platelet activation and reactive oxidative species generation are involved in the pathogenesis of IBD. We examined the inhibitory effects of a selective phosphodiesterase-3 inhibitor, cilostazol (CZ), and two antioxidants, enzymatically modified isoquercitrin (EMIQ) and α-lipoic acid (ALA), against dextran sulphate sodium (DSS)-induced colitis. BALB/c mice were treated with 0.3% CZ, 1.5% EMIQ, and 0.2% ALA in their feed. Colitis was induced by administering 5% DSS in drinking water for 8days. The inhibitory effects of these substances were evaluated by measuring relevant clinical symptoms (faecal blood, diarrhoea, and body weight loss), colon length, plasma cytokine and chemokine levels, whole genome gene expression, and histopathology. Diarrhoea was suppressed by each treatment, while CZ prevented shortening of the colon length. All treatment groups exhibited decreased plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α compared with the DSS group. Microarray analysis showed that cell adhesion, cytoskeleton regulation, cell proliferation, and apoptosis, which might be related to inflammatory cell infiltration and mucosal healing, were affected in all the groups. DSS-induced mucosal injuries such as mucosal loss, submucosal oedema, and inflammatory cell infiltration in the distal colon were prevented by CZ or antioxidant treatment. These results suggest that anti-inflammatory effects of these agents reduced DSS-induced mucosal injuries in mice and, therefore, may provide therapeutic benefits in IBD.

Study of the therapeutic effects of Lactobacillus and α-lipoic acid against dimethylnitrosamine-induced liver fibrosis in rats

Abstract Lactobacillus (LB) and α-lipoic acid (ALA) were investigated to compare their protective effects against dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Animals were either injected intraperitoneally with DMN to induce hepatic fibrosis, or were left untreated (negative control). For the DMN + LB and DMN + ALA treatment groups, at two weeks of DMN treatment LB or ALA was added to the feed and supplementation continued until the experimental endpoint at sixty days. At the study endpoint, expression of IL-1β, IL-6, IL-10, TNF-α, IFN-γ, TGF-β1, COL1-α1 genes and the concentration of glutathione and malondialdehyde were measured in liver tissues, while GOT, GPT, and ALP concentrations were measured in blood. Body weights remained higher in NC and DMN + LB groups compared to DMN and DMN + ALA groups, while activity of GOT and GPT in serum was lower in DMN + LB and DMN + ALA groups compared to the DMN group. Compared to other treatment groups, in the DMN group expression of both TGF-β1 and, COL1-α1 mRNAs and pro-inflammatory cytokines increased, while that of 1L-10 decreased. Furthermore, LB and ALA treatments increased antioxidant activity of glutathione and decreased malondialdehyde in comparison to the DMN group. Between LB and ALA treatments, glutathione concentration was higher in the DMN + LB group, while malondialdehyde was lower. Our results indicate that both LB and ALA exert hepatoprotective effects against DMN-induced liver fibrosis. Their beneficial effects may be partly associated with down-regulation of both TGF-β1 and COL1-α1 signaling, which may be accounted for reduction of increased oxidative stress and TNF-α production.

α-Tocopherol supplementation reduces biomarkers of oxidative stress in children with Down syndrome: a randomized controlled trial.

Down syndrome (DS) is the most common human chromosomal abnormality. It is characterized by mental retardation and several metabolic disturbances, including elevated oxidative stress, which may be causally linked. Treatment with dietary antioxidants has been suggested as a potential method to alleviate the oxidative damage and retardation of DS patients, but prior supplementation work has been equivocal. To evaluate the effects of supplementation with antioxidants α-tocopherol and α-lipoic acid (ALA) on oxidative stress biomarkers in DS children. Ninety-three DS children aged 7-15 years from both sexes were randomly allocated to three groups: α-tocopherol (400 IU/day), ALA (100 mg/day) and placebo. The intervention period was 4 months. A healthy control group consisted 26 non-DS siblings. Serum thiobarbituric acid reactive substances (TBARS) and urinary 8-hydroxy-2'-deoxyguanosine (8OHdG) were used as biomarkers of oxidative stress. DS children had greater levels of baseline oxidative stress than their siblings. Moreover, males had greater levels of 8OHdG than females (P<0.001) but there was no significant association between age and biomarkers of oxidative stress. Serum levels of TBARS did not change significantly over time, or relative to placebo. Although urinary 8OHdG concentrations decreased significantly in both α-tocopherol and ALA, groups compared with the baseline levels (P<0.001), mean final levels of urinary 8OHdG concentrations differed significantly only between α-tocopherol and placebo groups (P<0.01). α-Tocopherol supplementation of the diets of DS children may attenuate oxidative stress at the DNA level.