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Recent epidemiological and experimental studies have increasingly highlighted the association between environmental pollution, especially ultrafine particulate matter (PM), and the risk of neurodegenerative diseases, such as Parkinson’s disease (PD). These previous studies suggest a potential mechanism by which ultrafine PM contributes to neuronal damage through processes, such as iron accumulation and oxidative stress. In this study, we aimed to elucidate the effects of ultrafine PM on ferroptosis, an iron-dependent form of cell death, in the mouse substantia nigra pars compacta (SNc) and to evaluate the protective role of α-lipoic acid (ALA). Mice were exposed to ultrafine diesel exhaust particles (ufDEP), a type of ultrafine PM, intranasally and injected ALA intraperitoneally for seven consecutive days. Iron accumulation and lipid peroxidation were significantly increased, and antioxidant capacity was significantly decreased in the SNc after ufDEP exposure, highlighting the deleterious effects of ufDEP on tyrosine hydroxylase (TH)-positive neurons. In contrast, ALA treatment effectively mitigated these effects by reducing iron accumulation, decreasing lipid peroxidation, and restoring antioxidant levels, resulting in the protection of TH-positive neurons from ferroptotic damage. Our results provide evidence that ufDEP can induce ferroptosis in dopaminergic neurons in the SNc, potentially contributing to PD pathogenesis. Furthermore, ALA showed protective effects against ufDEP-induced ferroptotic damage, suggesting its potential as a therapeutic intervention for PD. [ABSTRACT FROM AUTHOR]

AIM: This study aims to investigate the protective effect of α-lipoic acid (α-LA) against alcohol-induced damage in H9c2 rat cardiomyocytes and to explore the underlying mechanisms. METHODS: An alcohol-induced injury model of H9c2 cells was established, and the cells were divided into 4 groups: control group, alcohol group, α-LA group, and alcohol+α-LA group. Additionally, H9c2 cells overexpressing aldehyde dehydrogenase 2 (ALDH2) were created and further divided into 6 groups: normal control group, normal cells treated with alcohol group, normal cells treated with alcohol+ α -LA group, ALDH2 overexpression group, ALDH2-overexpressing cardiomyocytes treated with alcohol group, and ALDH2-overexpressing cardiomyocytes treated with alcohol+α-LA group. Cell proliferation was assessed using 5-ethynyl-2'-deoxyuridine (EdU) staining. Reactive oxygen species (ROS) levels in each group were measured using dihydroethidium (DHE) staining, while the expression levels of ALDH2, silent information regulator 1 (SIRT1), heme oxygenase 1 (HO1) and P53 proteins were detected by Western blot analysis. RESULTS: (1) Alcohol exposure resulted in a decrease in the proliferation of H9c2 cells and an increase in intracellular oxidative stress, evidenced by elevated ROS levels and decreased expression of related proteins (ALDH2, SIRT1 and HO1) . However, α-LA treatment significantly mitigated the decline in cell proliferation and the oxidative stress induced by alcohol. (2) Alcohol may induce cellular senescence, as demonstrated by the up-regulation of P53 expression, which were reversed by α-LA. (3) The H9c2 cells with high ALDH2 expression markedly improved the cell proliferation in the presence of alcohol, suppressed the ROS production, prevented the down-regulation of oxidative stress-related proteins (ALDH2, SIRT1 and HO1), and reversed the enhanced expression of the senescence marker P53. CONCLUSION: Treatment with α -LA may counteract oxidative stress and attenuate cellular senescence by activating ALDH2, thereby protecting cardiomyocytes from alcohol-induced damage. [ABSTRACT FROM AUTHOR]

In order to mitigate the adverse effects of high carbohydrates on largemouth bass and to investigate the feasibility of LA as a feed additive, the present study observed the effects of added α-lipoic acid (LA) on growth performance, glucose metabolism and immunity in largemouth bass fed on high dietary carbohydrates (10% α-cassava starch inclusion). A total of 315 juvenile largemouth bass (initial body weight, 5.09 ± 0.10 g) were divided into nine tanks (800 L) (upper radius 0.65 m × lower radius 0.5 m × height 1 m), with each holding 35 fish. Three iso-nitrogenous and iso-lipidic diets supplementing with 0 g/kg, 0.5 g/kg and 1 g/kg LA (LA0, LA500, LA1000) were designed to feed juvenile largemouth bass on a satiation diet twice daily for eight weeks with each diet feeding to triplicate groups. The results indicated that the performance in growth was significantly enhanced by the addition of dietary LA (p < 0.05). Meanwhile, hepatic glycogen content was significantly reduced (p < 0.05), and the expression of genes relating to insulin pathway and glycolysis significantly increased with LA inclusion (p < 0.05). The relative expression of insulin receptor a (ira) in the LA500 group was the highest, while the relative expression of glycerol kinase (gk), phosphofructokinase liver type (pfkl) and phosphoenolpyruvate carboxykinase (pepck) was the highest in the LA1000 group (p < 0.05). In addition, LA supplementation significantly increased the activity of lysozyme, which reached its maximum value in the LA500 group (p < 0.05). LA supplementation also promoted the expression of genes relating to anti-inflammatory and inhibited the expression of pro-inflammatory related genes (p < 0.05). Above all, the dietary addition of LA could improve performance in growth, alleviated hepatic glycogen deposition, and improved the immunity function of largemouth bass fed on high dietary carbohydrates. This provides us with ideas to mitigate the adverse effects of high carbohydrates on largemouth bass in actual production and provides a basis for the application of LA in aquatic biology. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer among women worldwide, and adjuvant radiotherapy (RT) following tumor removal is one of the most commonly used treatments for breast cancer. However, the high risk of tumor recurrence and inevitable radiation skin injury after RT remain fatal problems, seriously challenging the patient's postoperative rehabilitation. Herein, a multifunctional poly (lipoic acid)-based hydrogel is constructed through one-step heating the mixture of α-lipoic acid (LA)/arginine (Arg)/silk fibroin (SF), without introducing any non-natural molecules. The multiple synergistic interactions among LA, Arg, and SF not only enhance the solubilization of LA in aqueous systems but also stabilize poly(lipoic acid) through strong salt bridge hydrogen bonds and ionic hydrogen bonds. Intriguingly, the LA-based surfactant induced β-sheet transformation of SF can further modulate the bulk strength of the hydrogel. Regulating the content of LA in hydrogels not only allows efficient control of hydrogel bioactivity but also enables the evolution of hydrogels from injectable forms to adhesive patches. Based on the different biological activities and forms of hydrogels, they can be implanted internally or applied externally on the mice's skin, achieving simultaneous prevention of tumor recurrence post-surgery and assistance in treating radiation-induced skin damage after radiotherapy.

Photothermal elastomers are recognized as smart flexible materials that can rapidly and effectively convert light energy into heat energy. However, there has been a lack of adequate focus on tackling the sustainability challenges of photothermal elastomers, particularly in terms of material selection, the integration of complex functionalities, and final disposal. A fully bio‐derived photothermal elastomer (BPTE) produced through a simple and chemical‐free approach is introduced, utilizing alkali lignin, lipoic acid, and phytic acid as bio‐derived feedstocks. The BPTE exhibits an adaptive polymeric network crosslinked by dynamic covalent disulfide bonds and multiple hydrogen bonds, endowing it with dual‐mode photothermal conversion capability, robustness, stretchability, rapidly self‐healing property, hydrophobicity, swelling resistance, self‐adhesion, full recyclability, and degradability. The BPTE is further demonstrated as a next‐generation solution for photothermal generators, light‐driven actuators, photothermal antibacterial dressings, and photothermal fibers. The versatility of BPTE opens avenues for innovative smart devices and systems with significant potential in energy conversion, soft robotics, medical treatment, and smart clothing. With outstanding photothermal performances, full recyclability, and biodegradability, these fully bio‐based elastomers present an attractive prospect for the development of the advanced smart photothermal products. [ABSTRACT FROM AUTHOR]

Background/Objectives: Diabetes mellitus (DM) is a complex and heterogenous disease classified as a group of metabolic disorders characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. It leads to various complications, some of which are macrovascular or microvascular complications, like diabetic polyneuropathy (DPN), having a profound impact on patients' quality of life. Oxidative stress (OS) is one of the significant mechanisms in the development and progression of DPN. Thus, targeting OS pathways by antioxidants, such as α-lipoic acid (ALA), could represent a promising therapeutic strategy for alleviating neuropathic symptoms. The aim of our study was to evaluate whether short-term (from 4 to 9 days) intravenous administration of ALA could cause any measurable improvement in subjects with DM. Methods: Sixteen subjects with DM (six type 1 and ten type 2) and sixteen nondiabetic subjects matched by sex and age were recruited to this study. Only subjects with DM received treatment with ALA (600 mg daily). Pain intensity and biomarkers of DNA damage including plasma concentration of 8-hydroxy-2′-deoxyguanosine (8-OHdG), frequency of micronucleated lymphocytes (MN), and frequency of sister-chromatid exchanges (SCEs), were measured before and after the treatment with ALA. Results: Pain intensity and 8-OHdG levels were significantly lower in DM subjects after the ALA treatment than before the treatment. However, no changes in the frequency of SCEs and MN were observed. Conclusions: Our results show some evidence that even a short-term intravenous treatment with ALA could be beneficial for diabetic subjects, reducing pain intensity and concentration of 8-OHdG in blood plasma. [ABSTRACT FROM AUTHOR]

Consumption of a high-fat diet is accompanied by the risks of obesity and early onset of age-associated complications for which dietary interventions are imperative to combat. α-lipoic acid has been shown to hinder diet-induced obesity and induce lifespan-extending efficacy in model organisms. In this study, α-lipoic acid was investigated for its efficacy in improving lifespan and stress resistance in the Canton-S strain of Drosophila melanogaster fed with a high-fat diet. Furthermore, as mating status significantly impacts survival in fruit flies, flies were reared in two experimental groups—group one, in which males and females were bred together, and group two, in which males and females were bred separately. In group one, α-lipoic acid improved the mean lifespan, reduced the fecundity of females, and reduced the mean body weight of flies at a dose range of 2–2.5 mM, respectively. In group two, α-lipoic acid improved the mean lifespan, reduced the fecundity of females, and reduced the mean body weight of flies at a dose range of 1–2.5 mM, respectively. Improved climbing efficiency was observed with α-lipoic acid at the dose range of 1.5–2.5 mM in flies of group one and 1–2.5 mM in flies of group two, respectively. Administration of α-lipoic acid improved resistance to oxidative stress in only female flies of group one at 2.5 mM, whereas in group two, both male and female flies exhibited enhanced resistance to oxidative stress with α-lipoic acid at a dose range of 2–2.5 mM, respectively. Male and female flies of only group one showed improved resistance to heat shock stress with α-lipoic acid at a dose range of 2–2.5 mM. Only female flies of group two exhibited a slight improvement in recovery time following cold shock with α-lipoic acid only at 2.5 mM. No significant change in resistance to starvation stress was observed with any dose of α-lipoic acid in either group of flies. To summarize, data from this study suggested a probable dose and gender-dependent efficacy of α-lipoic acid in flies fed with a high-fat diet, which was significantly influenced by the mating status of flies due to varied rearing conditions. [ABSTRACT FROM AUTHOR]

Alpha lipoic acid (α-LA) is a powerful antioxidant, which can reduce oxidative damage and inflammation in the host. In previous research, we found that 600 mg/kg α-LA supplemented in the diet could improve the activity of antioxidant enzymes and regulate the secretion of inflammatory factors in rumen of sheep. However, the mechanism of α-LA driving the antioxidant capacity in rumen of sheep remains unknown. The aim of this current research was to investigate the role of α-LA in antioxidant and inflammatory processes in the rumen of sheep. Transcriptomic and metabolomic analyses were performed to assess the variation of genes and metabolites of rumen epithelial tissue in sheep induced in the LA (600 mg/kg α-LA) group compared with the CTL (0 mg/kg α-LA) group. The results showed that some discovered core genes in the rumen epithelial tissue were negatively correlated with antioxidant activity. G6PD and HK2, the downregulated and upregulated core genes in the comparison of LA/CTL, were enriched in the pentose phosphate pathway (PPP) and the pathways of mannose and oligosaccharide metabolism, respectively. The PPP is a metabolic pathway within cells, primarily functioning to produce nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate. The differential metabolites were enriched in the pathway of 2-oxocarboxylic acid metabolism, which improves the antioxidant capacity of the rumen epithelium by increasing enzymatic activities of SOD. In conclusion, the present study demonstrated that α-LA improved antioxidant activity by regulating PPP and 2-oxocarboxylic acid metabolism. This study will provide a theoretical basis for the application of α-LA in the raising of sheep. [ABSTRACT FROM AUTHOR]

Background: In recent years, minimally invasive treatment options for lumbar disc herniation, such as percutaneous laser disc decompression (PLDD), have been introduced to avoid more invasive surgical methods. Combining these minimally invasive approaches with nutraceuticals that are effective in neuroprotection and pain management may lead to better long-term outcomes. Methods: The present study evaluated the beneficial effects of a new oral food supplement composed of acetyl-L-carnitine, α-lipoic acid, quercetin, bromelain, pantothenic acid, and vitamins C, B1, B2, B6, and B12 in patients with neuropathic pain due to herniated lumbar discs treated with PLDD. Patients were divided into two groups of 26 patients each: group A underwent PLDD alone, while group B underwent PLDD followed by a dietary supplement for two months after surgery. Preoperative VAS scores for leg pain were recorded for both groups and no significant difference was observed (8.7 for Group A and 8.6 for Group B). Results: In Group A, the mean postoperative VAS score for leg pain at a 1-month follow-up was 2.5, which remained stable at 3 months. In Group B, the mean postoperative VAS score was 2.0 at 1-month and improved to 1.6 at the 3-month follow-up. According to self-reported leg pain assessments, 66.5% of the patients using the dietary supplement reported a significantly better pain condition, and 43.5% reported a somewhat better situation. In contrast, 7.7% of the patients who underwent PLDD alone reported no changes in leg pain at the final follow-up. Conclusions: The results of our study indicate that the oral food supplement could provide a safe and effective treatment in patients with painful radiculopathy, enhancing the recovery of sensory fiber function in lumbar nerve roots after surgical lumbar disc decompression. [ABSTRACT FROM AUTHOR]

Oxytetracycline (OTC) is a widely employed antibiotic in veterinary treatment and in the prevention of infections, potentially leaving residues in animal-derived food products, such as milk, that are consumed by humans. Given the detrimental effects of prolonged human exposure to antibiotics, it has become imperative to develop precise and sensitive methods for monitoring the presence of OTC in food. Herein, we describe the development and results of a preliminary label-free electrochemical aptasensor with antifouling properties designed to detect OTC in milk samples. The sensor was realized by modifying a gold screen-printed electrode with α-lipoic acid–NHS and an amine-terminated aptamer. Different electrochemical techniques were used to study the steps of the fabrication process and to quantify OTC in the presence of the Fe(CN)64−/Fe(CN)63− redox couple The detectable range of concentrations satisfy the maximum residue limits set by the European Union, with an limit of detection (LOD) of 14 ng/mL in phosphate buffer (BP) and 10 ng/mL in the milk matrix, and a dynamic range of up to 500 ng/mL This study is a steppingstone towards the implementation of a sensitive monitoring method for OTC in dairy products. [ABSTRACT FROM AUTHOR]

Objective is to examine the background of IAS and the variations in drugs that trigger it among patients who have been genetically tested, aiming to deepen our understanding of this condition. HLA Analysis of 68 cases showed that DR4 is predominant, especially in individuals of East Asian descent, notably in DRB1 *0406. Methimazole was the primary drug associated with IAS in these populations, while in Caucasian individuals, the emphasis was on DRB1 *0403, with lipoic acid being the common inducer. The key factor determining disease risk is the combination of chromosomal allele variations, with HLA class II allele DR4 positive patients showing a strong association with DQA1 *0301/DQB1 *0302. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the impacts of incorporating α-lipoic acid (LA) in a high-fat diet (HFD) on growth, lipid metabolism and mitochondrial function in Lateolabrax maculatus. A normal-fat diet (NFD, 10 % lipid), a high-fat diet (HFD, 16 % lipid) and three LA-added HFD (200, 400, or 600 mg kg−1 LA) were prepared and fed to five group of L. maculatus for 57 days. Supplementation of 400 mg kg−1 LA to the HFD improved growth performance and feed utilization. LA treatment reduced the lipids concentration in serum and liver. Moreover, application of 400 mg kg−1 LA in HFD notably decreased the activity of transaminases in serum. Liver oil red O staining results revealed the larger area of red lipid droplets in HFD group compared to the NFD group. Also, abdominal fat HE staining results showed larger adipocytes in the HFD group. Interestingly, LA application led to a reduction in the area of red lipid droplets and a decrease in the size of adipocytes. Furthermore, LA addition alleviated the HFD-induced oxidative stress as identified by enhanced mitochondrial citrate synthase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase activities. Meanwhile, LA administration induced the activation of mitochondrial biogenesis, and up-regulated the expression of autophagy-related genes. In conclusion, LA incorporation into HFD for L. maculatus promoted growth performance, enhanced liver mitochondrial function, and mitigated excessive fat accumulation in the liver.

The aim of this experiment was to investigate the effects of guanidine acetic acid (GAA) and α -lipoic acid (LA) supplementation in diets on growth performance, blood parameters and meat quality. A total of 24 healthy male sheep with similar body weight and good constitution were randomly divided into four groups: control group (fed a basal diet), guanidine acetic acid group (fed a basal diet supplemented with 1 500 mg/kg guani‐dine acetic acid) and α-lipoic acid group (fed a basal diet supplemented with 1 500 mg/kg guanidine acetic acid). 600 mg/kg α-lipoic acid was added to the basic diet and mixed group (1 500 mg/kg guanidi‐ noacetic acid and 600 mg/kg α -lipoic acid were added to the basic diet), the experiment lasted for 60 days, and the growth performance, blood indexes, slaughter performance indexes and meat quality in‐ dexes were determined. The results showed as follows: the average daily feed intake of α -lipoic acid group and mixed group was significantly higher than that of control group (P<0.05); the contents of glutamicoxalacetic transaminase and urea in blood of guanidine acetic acid group were significantly higher than those of control group (P<0.05). The content of interleukin-6 in control group was significantly higher than that in other three groups (P<0.05). The content of malondialdehyde in guanidine acetic acid group was significantly lower than that in control group (P<0.05). The liver index of mixed group was higher than that of control group, guanidino acetic acid group and α-lipoic acid group (P<0.05). In terms of meat quality, the shear force of control group was significantly higher than that of guanidino acetic acid group, α-lipoic acid group and mixed group (P<0.05). The muscle protein content of control group was significantly lower than that of guanidino acetic acid group, α -lipoic acid group and mixed group (P< 0.05), and the muscle fat content of control group was significantly higher than that of α -lipoic acid group and mixed group (P<0.05). The muscle nitrogen content of α-lipoic acid group and mixed group was significantly higher than that of control group (P<0.05); the levels of capric acid (C10∶0), myristylic acid (C14∶1), pentadecanoic acid (C15∶1), palmitoleic acid (C16∶1) and heptadecenoic acid (C17∶ 1) in guanidino acetic acid group were significantly higher than those in control group (P<0.05). In sum‐ mary, α-lipoic acid increased the feed intake of sheep, reduced the shear force of sheep muscle, im‐ proved muscle tenderness, and guanidine acetic acid increased the content of fatty acids in muscle. [ABSTRACT FROM AUTHOR]

Introduction: Heat stress has become a significant concern for the global poultry industry as a result of climate change. This condition can adversely affect growth, gut health, immune function, production levels, and reproductive performance, and can lead to lipid peroxidation in poultry. Therefore, this study aimed to evaluate Interleukin 6 and 10 immune responses, anti-oxidant indices, serum biochemistry, and hepatic and splenic histopathology of heat-stressed broiler chickens supplemented with α-lipoic acid (α-LA) in their diet. Materials and methods: A total of two hundred and four unsexed day-old Arbor acre broiler chicks were randomly divided into four treatment groups and replicated three times to receive α-LA at 0, 50, 100, and 200 mg/kg, respectively in a completely randomized design for 42 days after a one-week adjustment period. The average temperature in the morning and afternoon was 27.9°C and 35.1°C, respectively, while the morning and afternoon humidity was 73.1% and 44.1% respectively. Feed and water were provided ad libitum. At the end of the feeding trial, samples were taken for cytokines (interleukin-6 and 10), anti-oxidant, serum biochemistry, and hepatic and splenic histopathology analyses. Results: An inverse relationship was observed between pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines whereby, IL-6 levels decreased while IL-10 levels increased relative to increasing α-LA levels in treatment groups. The treatment groups also indicated an increasing trend with rising levels of α-LA for superoxide dismutase, catalase, glutathione, and total antioxidant capacity. The α-LA significantly influenced malondialdehyde production, showing its reduction with rising levels of α-LA. A decrease in serum glucose and low-density lipoproteins was observed with increasing levels of α-LA, while high-density lipoproteins increased with increasing levels of α-LA. Cholesterol, triglycerides, very low-density lipoproteins, aspartate transaminase, alanine transaminase, and alkaline phosphate remained unchanged across the treatment groups. Conclusion: α-LA supplementation at 200mg/kg in diet had the highest effects on immune responses of interleukin 6 and 10, antioxidant, serum biochemical indices, and histopathology of heat-stressed broiler chickens. [ABSTRACT FROM AUTHOR]

α-lipoic acid is a naturally occurring compound with potent antioxidant properties that helps protect cells and tissues from oxidative stress. Its incorporation into nanoplatforms can affect factors like bioavailability, stability, reactivity, and targeted delivery. Nanoformulations of α-lipoic acid can significantly enhance its solubility and absorption, making it more bioavailable. While α-lipoic acid can be prone to degradation in its free form, encapsulation within nanoparticles ensures its stability over time, and its release in a controlled and sustained manner to the targeted tissues and cells. In addition, α-lipoic acid can be combined with other compounds, such as other antioxidants, drugs, or nanomaterials, to create synergistic effects that enhance their overall therapeutic benefits or hinder their potential cytotoxicity. This review outlines the advantages and drawbacks associated with the use of α-lipoic acid, as well as various nanotechnological approaches employed to enhance its therapeutic effectiveness, whether alone or in combination with other bioactive agents. Furthermore, it describes the engineering of α-lipoic acid to produce poly(α-lipoic acid) nanoparticles, which hold promise as an effective drug delivery system. [ABSTRACT FROM AUTHOR]

Periodontitis, a common chronic inflammatory disease caused by pathogenic bacteria, can be treated with diverse biomaterials by loading drugs, cytokines or proteins. However, these biomaterials often show unsatisfactory therapeutic efficiency due to their poor adhesion, short residence time in the wet and dynamic oral cavity and emerging drug resistance. Here we report a wet-responsive methacrylated gelatin (GelMA)-stabilized co-enzyme polymer poly(α-lipoic acid) (PolyLA)-based elastic patch with water-induced adhesion and softening features. In PolyLA-GelMA, the multiple covalent and hydrogen-bonding crosslinking between PolyLA and GelMA prevent PolyLA depolymerization and slow down the dissociation of PolyLA in water, allowing durable adhesion to oral periodontal tissue and continuous release of LA-based bioactive small molecule in periodontitis wound without resorting external drugs. Compared with the undifferentiated adhesion behavior of traditional adhesives, this wet-responsive patch demonstrates a favorable periodontal pocket insertion ability due to its non-adhesion and rigidity in dry environment. In vitro studies reveal that PolyLA-GelMA patch exhibits satisfactory wet tissue adhesion, antibacterial, blood compatibility and ROS scavenging abilities. In the model of rat periodontitis, the PolyLA-GelMA patch inhibits alveolar bone resorption and accelerates the periodontitis healing by regulating the inflammatory microenvironment. This biomacromolecule-stabilized coenzyme polymer patch provides a new option to promote periodontitis treatment.

Excessive lipid deposition affects hepatic homeostasis and contributes to the development of insulin resistance as a crucial factor for the deterioration of simple steatosis to steatohepatitis. So, it is essential to search for an effective agent for a new therapy for hepatic steatosis development before it progresses to the more advanced stages. Our study aimed to evaluate the potential protective effect of α-lipoic acid (α-LA) administration on the intrahepatic metabolism of sphingolipid and insulin signaling transduction in rats with metabolic dysfunction-associated steatotic liver disease (MASLD). The experiment was conducted on male Wistar rats subjected to a standard diet or a high-fat diet (HFD) and an intragastrically α-LA administration for eight weeks. High-performance liquid chromatography (HPLC) was used to determine sphingolipid content. Immunoblotting was used to measure the expression of selected proteins from sphingolipid and insulin signaling pathways. Multiplex assay kit was used to assess the level of the phosphorylated form of proteins from PI3K/Akt/mTOR transduction. The results revealed that α-LA decreased sphinganine, dihydroceramide, and sphingosine levels and increased ceramide level. We also observed an increased the concentration of phosphorylated forms of sphingosine and sphinganine. Changes in the expression of proteins from sphingolipid metabolism were consistent with changes in sphingolipid pools. Treatment with α-LA activated the PI3K/Akt/mTOR pathway, which enhanced the hepatic phosphorylation of Akt and mTOR. Based on these data, we concluded that α-lipoic acid may alleviate glucose intolerance and may have a protective influence on the sphingolipid metabolism under HFD; thus, this antioxidant appears to protect from MASLD development and steatosis deterioration. [ABSTRACT FROM AUTHOR]

To investigate the effect of tanshinone IIA sulfonate sodium combined with α-Lipoic acid on fasting blood sugar (FPG), 2h postprandial blood glucose (2hPG), total cholesterol (TG), triacylglycerol (TC) and therapeutic effect in patients with diabetes peripheral neuropathy (DPN). The control group (n=52) was treated with tanshinone IIA sodium sulfonate alone. The study group was treated with α-Lipoic acid and tanshinone IIA sodium sulfonate. The changes in blood glucose, blood lipid levels, oxidative stress indicators and the improvement of nerve function conduction of both two groups were compared. After treatment, study group’s FPG, 2hPG, TG and TC were found to be lower than the control group (P<0.05). The levels of Super oxide dismutase (SOD) and nitric oxide (NO) in the study group were higher than those in the control group. The study group had lower Malondialdehyde (MDA) (P<0.05). The study group had higher nerve motor conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) (P<0.05). Tanshinone IIA sulfonate sodium combined with α-Lipoic acid can improve DPN patients’ blood glucose and lipid levels, alleviate the oxidative stress reaction of the body, promote the recovery of nerve conduction function and enhance the therapeutic effect. [ABSTRACT FROM AUTHOR]

Obesity is a metabolic disorder with excessive body fat accumulation, increasing incidence of chronic metabolic diseases. Hypertrophic obesity is associated with local oxidative stress and inflammation. Herein, we evaluated the in vitro activity of micromolar concentrations of α-lipoic acid (ALA) on palmitic acid (PA)-exposed murine hypertrophic 3T3-L1 adipocytes, focussing on the main molecular pathways involved in adipogenesis, inflammation, and insulin resistance. ALA, starting from 1 µM, decreased adipocytes hypertrophy, reducing PA-triggered intracellular lipid accumulation, PPAR-γ levels, and FABP4 gene expression, and counteracted PA-induced intracellular ROS levels and NF-κB activation. ALA reverted PA-induced insulin resistance, restoring PI3K/Akt axis and inducing GLUT-1 and glucose uptake, showing insulin sensitizing properties since it increased their basal levels. In conclusion, this study supports the potential effects of low micromolar ALA against hypertrophy, inflammation, and insulin resistance in adipose tissue, suggesting its important role as pharmacological supplement in the prevention of conditions linked to obesity and metabolic syndrome. [ABSTRACT FROM AUTHOR]

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AbstractOsteoporosis is a common disease among the ageing society. Oxidative stress caused by excessive accumulation of reactive oxygen species (ROS) is the aetiology of osteoporosis. α-Lipoic acid (ALA) is an antioxidant in the body, which can eliminate excess ROS in the body and inhibits levels of oxidative stress in cells. Herein, we designed PEGylated hollow gold nanoparticles (HGNPs) loaded with ALA (mPEG@HGNPs-ALA) to remove ROS in the treatment of osteoporosis. First, mPEG@HGNPs with a particle size of ∼63 nm has been successfully synthesized. By comparing the drug loading of mPEG@HGNPs, it was concluded that the optimal mass ratio of mPEG@HGNPs (calculated by the amount of gold) to ALA was ∼1:2. ABTS antioxidant assay showed that free radical removal ability. In vitro results revealed that the preparation had good biocompatibility. At the gold concentration of 1–150 μg/mL, the cell viability of mPEG@HGNPs was more than 100%, which indicated that it could promote the proliferation of osteoblasts. What’s more, mPEG@HGNPs-ALA could effectively remove the ROS caused by H2O2 injury and improve the cell viability. According to these results, it can be considered that mPEG@HGNPs-ALA has the potential to treat osteoporosis.

With the rapid development of “Internet of Things” and human-computer interaction techniques, it is essential and urgent to develop facile and scalable fabrication platforms for stretchable flexible sensor. Herein, we report a facile strategy of using the green choline chloride–acrylamide deep eutectic solvent (CC-AM DES) to guide the in-situ ring-opening polymerization of α-lipoic acid (LA), leading to the successful development of a stretchable ionogel material. The as-prepared ionogel from CC-AM DES system exhibits multifunctional merits including the super stretchability (>9000%), 100% UV-blocking ability, tunable adhesiveness (29–414 kPa), high ionic conductivity (4.45 × 10−4 S/cm), and ideal anti-freezing (–27 °C). In addition, this outstanding ionogel can be readily coated on various material substrates with designable shapes and patterns. Owning to these promising properties and performances, a scalable flexible strain sensor is assembled from the ionogel and exhibits stable resistance variations (R/R0) towards multiple external mechanical stimulus. This study provides a green, cost effective, and scalable strategy to fabricate ionogel materials and multifunctional flexible strain sensors, showing a great potential in the fast-emerging highly stretchable wearable/flexible electronics.

Alpha lipoic acid (α-LA) is a powerful antioxidant, which can reduce oxidative damage and inflammation in the host. In previous research, we found that 600 mg/kg α-LA supplemented in the diet could improve the activity of antioxidant enzymes and regulate the secretion of inflammatory factors in rumen of sheep. However, the mechanism of α-LA driving the antioxidant capacity in rumen of sheep remains unknown. The aim of this current research was to investigate the role of α-LA in antioxidant and inflammatory processes in the rumen of sheep. Transcriptomic and metabolomic analyses were performed to assess the variation of genes and metabolites of rumen epithelial tissue in sheep induced in the LA (600 mg/kg α-LA) group compared with the CTL (0 mg/kg α-LA) group. The results showed that some discovered core genes in the rumen epithelial tissue were negatively correlated with antioxidant activity. G6PD and HK2, the downregulated and upregulated core genes in the comparison of LA/CTL, were enriched in the pentose phosphate pathway (PPP) and the pathways of mannose and oligosaccharide metabolism, respectively. The PPP is a metabolic pathway within cells, primarily functioning to produce nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate. The differential metabolites were enriched in the pathway of 2-oxocarboxylic acid metabolism, which improves the antioxidant capacity of the rumen epithelium by increasing enzymatic activities of SOD. In conclusion, the present study demonstrated that α-LA improved antioxidant activity by regulating PPP and 2-oxocarboxylic acid metabolism. This study will provide a theoretical basis for the application of α-LA in the raising of sheep.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronically relapsing inflammatory disease with severe diarrhea, fatigue and weight loss. α‐Lipoic acid (LA), a well‐known antioxidant, is able to scavenge reactive oxygen species (ROS) and maintain a healthy cellular redox state. However, the role of LA in protecting IBD is still unclear. Hence the aim of this research was to investigate the protective effect of LA on dextran sulfate sodium salt‐induced ulcerative colitis (UC) and its underlying mechanism. RESULTS: Here, our findings showed that LA significantly alleviated UC symptoms and the overproduction of pro‐inflammatory cytokines in UC mice. In addition, LA treatment inhibited intestinal cell apoptosis by regulating the expression levels of p53/caspase‐3 pathway‐related protein in UC mice. Meanwhile, the inhibitory effects of LA on colonic oxidative stress and ferroptosis were revealed. Our study further demonstrated that LA treatment could regulate the Kelch‐like ECH‐associating protein 1 (Keap1)–nuclear factor E2‐related factor 2 (Nrf2) signaling pathway. Interestingly, we confirmed that LA inhibited ferroptosis by attenuating endoplasmic reticulum stress and suppressing apoptosis in erastin‐induced ferroptosis model in vitro. CONCLUSION: Taken together, this study's findings suggest that LA could be considered as a therapeutic agent protecting against IBD. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Livestock producers need new technologies to maintain the optimal health and well-being of their animals while minimizing the risks of propagating and disseminating pathogenic and antimicrobial-resistant bacteria to humans or other animals. Where possible, these interventions should contribute to the efficiency and profitability of animal production to avoid passing costs on to consumers. In this study, we examined the potential of nitroethane, 3-nitro-1-propionate, ethyl nitroacetate, taurine and L-cysteinesulfinic acid to modulate rumen methane production, a digestive inefficiency that results in the loss of up to 12% of the host's dietary energy intake and a major contributor of methane as a greenhouse gas to the atmosphere. The potential for these compounds to inhibit the foodborne pathogens, Escherichia coli O157:H7 and Salmonella Typhimurium DT104, was also tested. The results from the present study revealed that anaerobically grown O157:H7 and DT104 treated with the methanogenic inhibitor, ethyl nitroacetate, at concentrations of 3 and 9 mM had decreased (p < 0.05) mean specific growth rates of O157:H7 (by 22 to 36%) and of DT104 (by 16 to 26%) when compared to controls (0.823 and 0.886 h−1, respectively). The growth rates of O157:H7 and DT104 were decreased (p < 0.05) from controls by 31 to 73% and by 41 to 78% by α-lipoic acid, which we also found to inhibit in vitro rumen methanogenesis up to 66% (p < 0.05). Ethyl nitroacetate was mainly bacteriostatic, whereas 9 mM α-lipoic acid decreased (p < 0.05) maximal optical densities (measured at 600 nm) of O157:H7 and DT104 by 25 and 42% compared to controls (0.448 and 0.451, respectively). In the present study, the other oxidized nitro and organosulfur compounds were neither antimicrobial nor anti-methanogenic. [ABSTRACT FROM AUTHOR]

This study aimed to assess the impact of α-lipoic acid on the growth performance, antioxidant capacity and immunity in hybrid groupers (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatus) fed with a high-lipid diet. Groupers (8.97 ± 0.01 g) were fed six different diets, with α-lipoic acid content in diets being 0, 400, 800, 1200, 1600, and 2000 mg/kg, named S1, S2, S3, S4, S5, and S6, respectively. The results show that the addition of 2000 mg/kg α-lipoic acid in the diet inhibited the growth, weight gain rate (WGR), and specific growth rate (SGR), which were significantly lower than other groups. In serum, catalase (CAT) and superoxide dismutase (SOD) were significantly higher in the S5 group than in the S1 group. In the liver, CAT, SOD and total antioxidative capacity (T-AOC) levels were significantly increased in α-lipoic acid supplemented groups. α-lipoic acid significantly upregulated liver antioxidant genes sod and cat, anti-inflammatory factor interleukin 10 (il10) and transforming growth factor β (tgfβ) mRNA levels. Conclusion: the addition of 2000 mg/kg of α-lipoic acid inhibits the growth of hybrid groupers. In addition, 400–800 mg/kg α-lipoic acid contents improve the antioxidant capacity of groupers and have a protective effect against high-lipid-diet-induced liver oxidative damage. [ABSTRACT FROM AUTHOR]

Background: Kidney diseases are a major global health problem affecting millions of people. Despite this, there is as yet no effective drug therapy improving outcome in patients with renal disease. The aim of this study was to examine the nephroprotective effect of α-lipoic acid (ALA) in vitro and to examine the effect of ALA administered in vivo on the production of reactive sulfur species (RSS), including hydrogen sulfide (H2 S) and compounds containing sulfane sulfur. Methods: The effect of ALA was studied in vitro by determining the viability of human embryonic kidney cells (HEK293) in normoxic and hypoxic conditions as well as in vivo in two groups of chronic kidney disease (CKD) patients: non-dialyzed (ND) and undergoing continuous ambulatory peritoneal dialysis (PD) after 30 days of ALA supplementation. Results: The results revealed that the viability of HEK293 cells was significantly decreased by hypoxic conditions, while ALA administered during hypoxia increased the viability to the level observed in normoxic conditions. Studies performed in plasma of CKD patients after ALA supplementation suggested that ALA did not affect the parameters of oxidative stress, while significantly increased the level of reactive sulfane sulfur in both ND and PD patients suffering from CKD. The results suggest that ALA can exert nephroprotective effects which are related to sulfane sulfur production. [ABSTRACT FROM AUTHOR]

A novel, repeatable, and swift kinetic approach for determining α-lipoic acid (ALA) in sodium lauryl sulfate (SLS) micellar medium has been presented, and it has been connected to ALA determination in drug formulations. The approach is based on ALA inhibitory property. ALA (containing two sulfur atoms) forms a chelate with Hg2+, lowering the effective [Hg(II)], and ultimately, the Hg2+ catalyzed cyanide substitution rate from [Fe(CN)6]4– by 4-cyanopyridine (4-CNpy). Fixed times of 5 and 10 min were chosen under optimal reaction conditions with [4-CNpy] = 3.0 × 10–3 mol dm–3, pH 3.75 ± 0.02, Temp. = 298 ± 0.2 K, I = 0.1 mol dm–3 (NaClO4), [Fe(CN) ] = 2.5 × 10–4 mol dm–3, [Hg+2] = 6.0 × 10–5 mol dm–3, and [SLS] = 7.75 × 10–3 mol dm–3 to calculate the absorbance at 477 nm associated with the final substitution product [Fe(CN)5 4-CNpy]3–. ALA's inhibiting influence on the Hg2+ catalyzed cyanide substitution with 4-CNpy from [Fe(CN)6]4–, has been represented by a modified mechanistic approach. The concentration of ALA in various water specimens can be measured at the micro-level down to 1.0 × 10–6 mol dm–3 using the established kinetic spectrophotometric approach. The suggested method is highly reproducible and has been effectively applied to accurately quantify the ALA in pharmaceutical samples. Even as much as 1000 with [ALA], typical additives used in medications do not significantly hinder the determination of ALA. [ABSTRACT FROM AUTHOR]

α‐lipoic acid (LA), a coenzyme, has proved to have excellent antioxidant and antibacterial activities; however, its intrinsic hydrophobicity and metastability of polyLA remains a major challenge for the application of LA‐based bulk materials in biomedical field. Herein, a self‐stabilized LA‐based deep eutectic supramolecular polymer (LA‐DESP) adhesive is created by one‐step heating the mixture of LA and sodium α‐lipoate (LA‐Na) (S‐, R‐isomer, racemate) without introducing any exogenous stabilizing molecules. The underlying deep eutectic effect in LA/LA‐Na is unveiled to be originated from the multiple hydrogen bonds between polyLA and polyLA‐Na, which not only prevent polyLA depolymerization but also lower the melting point of LA‐DESP to the near body and pathological temperature. Copolymerization of LA and LA‐Na slows down the dissociation of polyLA‐Na, thus affording sustainable release of bioactive LA‐based small molecules and satisfactory antioxidant and antibacterial functions. Also, the LA‐DESP exhibits fast and tough adhesion to diverse substrates, including wet tissues, relying on its in situ curing property and rich carboxyl groups. The LA‐DESP is explored as a tissue sealant, which can well replace surgical suture to enhance the wound healing of skin incision in a rat model. The unprecedented deep eutectic effect will provide a new strategy for the development of LA‐based bioadhesives. [ABSTRACT FROM AUTHOR]

Alzheimer's disease manifests as a complex pathological condition, with neuroinflammation, oxidative stress and cholinergic dysfunction being a few of the many pathological changes. Due to the complexity of the disease, current therapeutic strategies aim at a multitargeted approach, often relying on a combination of substances with versatile and complementary effects. In the present study, a unique combination of α-lipoic acid, citicoline, extracts of leaves from olive tree and green tea, vitamin D3, selenium and an immune-supporting complex was tested in scopolamine-induced dementia in rats. Using behavioral and biochemical methods, we assessed the effects of the combination on learning and memory, and elucidated the mechanisms of these effects. Our results showed that, compared to its components, the experimental combination was most efficient in improving short- and long-term memory as assessed by the step-through method as well as spatial memory as assessed by T-maze and Barnes maze underlined by decreases in AChE activity (p < 0.05) and LPO (p < 0.001), increases in SOD activity in the cortex (p < 0.05) and increases in catalase (p < 0.05) and GPx (p < 0.01) activities and BDNF (p < 0.001) and pCREB (p < 0.05) levels in the hippocampus. No significant histopathological changes or blood parameter changes were detected, making the experimental combination an effective and safe candidate in a multitargeted treatment of AD. [ABSTRACT FROM AUTHOR]

Abstract With the rising demand for new cultivars of carnation, efficient transformation protocols are needed to enable the bioengineering of new traits. Here, we established a novel and efficient Agrobacterium-mediated transformation system using callus as the target explant for four commercial carnation cultivars. Leaf-derived calli of all cultivars were inoculated with Agrobacterium tumefaciens strain LBA4404 containing the plasmid pCAMBIA 2301 harboring genes for β-glucuronidase (uidA) and neomycin phosphotransferase (nptII). Polymerase chain reaction (PCR) and histochemical assays confirmed the presence of uidA and β-glucuronidase (GUS), respectively in transgenic shoots. The effect on transformation efficiency of medium composition and the presence of antioxidants during inoculation and co-cultivation was investigated. The transformation efficiency was increased in Murashige and Skoog (MS) medium lacking KNO3 and NH4NO3, and also in MS medium lacking macro and micro elements and Fe to 5% and 3.1% respectively, compared to 0.6% in full-strength medium. Transformation efficiency was increased dramatically to 24.4% across all carnation cultivars by the addition of 2 mg/l melatonin to nitrogen-depleted MS medium. Shoot regeneration was also doubled in this treatment. The establishment of this efficient and reliable transformation protocol can advance the development of novel carnation cultivars through molecular breeding approaches.

α-lipoic acid is a naturally occurring compound with potent antioxidant properties that helps protect cells and tissues from oxidative stress. Its incorporation into nanoplatforms can affect factors like bioavailability, stability, reactivity, and targeted delivery. Nanoformulations of α-lipoic acid can significantly enhance its solubility and absorption, making it more bioavailable. While α-lipoic acid can be prone to degradation in its free form, encapsulation within nanoparticles ensures its stability over time, and its release in a controlled and sustained manner to the targeted tissues and cells. In addition, α-lipoic acid can be combined with other compounds, such as other antioxidants, drugs, or nanomaterials, to create synergistic effects that enhance their overall therapeutic benefits or hinder their potential cytotoxicity. This review outlines the advantages and drawbacks associated with the use of α-lipoic acid, as well as various nanotechnological approaches employed to enhance its therapeutic effectiveness, whether alone or in combination with other bioactive agents. Furthermore, it describes the engineering of α-lipoic acid to produce poly(α-lipoic acid) nanoparticles, which hold promise as an effective drug delivery system.

The present work investigated the effect of α-lipoic acid (ALA) and caffeine-loaded chitosan nanoparticles (CAF-CS NPs) on obesity and its hepatic and renal complications in rats. Rats were divided into control, rat model of obesity induced by high fat diet (HFD), and obese rats treated with ALA and/or CAF-CS NPs. At the end of the experiment, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and the levels of urea, creatinine, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were determined in the sera of animals. In addition, malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) were measured in hepatic and renal tissues. Renal Na+, K+-ATPase was assessed. The histopathological changes were examined in the hepatic and renal tissues. Obese rats showed a significant increase in AST, ALT, ALP, urea, and creatinine. This was associated with a significant increase in IL-1β, TNF-α, MDA, and NO. A significant decrease in hepatic and renal GSH and renal Na+, K+-ATPase activity was recorded in obese rats. Obese rats also showed histopathological alterations in hepatic and renal tissues. Treatment with ALA and/or CAF-CS NPs reduced the weight of obese rats and ameliorated almost all the hepatic and renal biochemical and histopathological changes induced in obese rats. In conclusion, the present findings indicate that ALA and/or CAF-CS NPs offered an effective therapy against obesity induced by HFD and its hepatic and renal complications. The therapeutic effect of ALA and CAF-CS NPs could be mediated through their antioxidant and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

α-lipoic acid (LA) is an essential cofactor for mitochondrial dehydrogenases and is required for cell growth, metabolic fuel production, and antioxidant defense. In vitro, LA binds copper (Cu) with high affinity and as an endogenous membrane permeable metabolite could be advantageous in mitigating the consequences of Cu overload in human diseases. We tested this hypothesis in 3T3-L1 preadipocytes with inactivated Cu transporter Atp7a; these cells accumulate Cu and show morphologic changes and mitochondria impairment. Treatment with LA corrected the morphology of Atp7a-/-cells similar to the Cu chelator bathocuproinedisulfonate (BCS) and improved mitochondria function; however, the mechanisms of LA and BCS action were different. Unlike BCS, LA did not decrease intracellular Cu but instead increased selenium levels that were low in Atp7a-/- cells. Proteome analysis confirmed distinct cell responses to these compounds and identified upregulation of selenoproteins as the major effect of LA on preadipocytes. Upregulation of selenoproteins was associated with an improved GSH:GSSG ratio in cellular compartments, which was lowered by elevated Cu, and reversal of protein oxidation. Thus, LA diminishes toxic effects of elevated Cu by improving cellular redox environment. We also show that selenium levels are decreased in tissues of a Wilson disease animal model, especially in the liver, making LA an attractive candidate for supplemental treatment of this disease. [ABSTRACT FROM AUTHOR]

The term neurodegeneration with brain iron accumulation (NBIA) brings together a broad set of progressive and disabling neurological genetic disorders in which iron is deposited preferentially in certain areas of the brain. Among NBIA disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by pathologic variants in the PANK2 gene codifying the enzyme pantothenate kinase 2 (PANK2). To date, there are no effective treatments to stop the progression of these diseases. This review discusses the utility of patient-derived cell models as a valuable tool for the identification of pharmacological or natural compounds for implementing polytarget precision medicine in PKAN. Recently, several studies have described that PKAN patient-derived fibroblasts present the main pathological features associated with the disease including intracellular iron overload. Interestingly, treatment of mutant cell cultures with various supplements such as pantothenate, pantethine, vitamin E, omega 3, α-lipoic acid L-carnitine or thiamine, improved all pathophysiological alterations in PKAN fibroblasts with residual expression of the PANK2 enzyme. The information provided by pharmacological screenings in patient-derived cellular models can help optimize therapeutic strategies in individual PKAN patients. [ABSTRACT FROM AUTHOR]

Aggression, a highly prevalent behavior among all the psychological disorders having strong association with psychiatric imbalance, neuroendocrine changes and neurological disturbances (including oxidative stress & neuroinflammation) require both pharmacological and non-pharmacological treatments. Focusing the preclinical neuroendocrine determinants of aggression, this interventional study was designed to elucidate the curative effect of antioxidants on aggression in male mice. Adult albino male mice (n = 140) randomly divided into two main treatment groups for α-lipoic acid (ALA) and silymarin with 5 subgroups (n = 10) for each curative study, namely control, disease (aggression-induced), standard (diazepam, 2.5 mg/kg), low dose (100 mg/kg) and high dose (200 mg/kg) treatment groups of selected antioxidants. Resident-intruder paradigm and levodopa (L-dopa 375 mg/kg, p.o.) induced models were used for aggression. Effect of antioxidant treatment (i.e., 21 days bid) on aggression was assessed by evaluating the changes in aggressive behavior, oxidative stress biomarkers superoxide dismutase, catalase, glutathione, nitrite and malondialdehyde (SOD, CAT, GSH, nitrite & MDA), neurotransmitters (dopamine, nor-adrenaline and serotonin), pro-inflammatory cytokines tumor necrosis factor-α and interleukin- 6 (TNF-α & IL-6) along with serum testosterone examination. This study showed potential ameliorative effect on aggressive behavior with both low (100 mg/kg) and high (200 mg/kg) doses of antioxidants (ALA & silymarin). Resident-intruder or L-dopa induced aggression in male mice was more significantly tuned with ALA treatment than silymarin via down regulating both oxidative stress and inflammatory biomarkers. ALA also exhibited notable effects in managing aggression-induced disturbances on plasma testosterone levels. In conclusion, ALA is more effective than silymarin in attenuating aggression in mice. [ABSTRACT FROM AUTHOR]

A nanocomposite material based on halloysite and α-lipoic acid was studied. The kinetics of the degradation process of α-lipoic acid under the influence of ultraviolet radiation and thermal stress in its native state and in the composition of a halloysite-based nanocomposite were studied. The concentration of undegraded α-lipoic acid and the effect of the nanocomposite composition were determined by the HPLC method. It has been shown that adding α-lipoic acid to halloysite using a vacuum method allows for an increase in its resistance toward UV light of 84.4%, and the thermal resistance was also significantly improved. The composite based on halloysite and α-lipoic acid can be used to improve the resistance to photodegradation of pharmaceutical drugs or sunscreen cosmetics because this strategy preserves the biological active properties and shelf life of the α-lipoic acid. [ABSTRACT FROM AUTHOR]

High environment ammonia (HEA) poses a deadly threat to aquatic animals and indirectly impacts human healthy life, while nutritional regulation can alleviate chronic ammonia toxicity. α-lipoic acid exhibits antioxidative effects in both aqueous and lipid environments, mitigating cellular and tissue damage caused by oxidative stress by aiding in the neutralization of free radicals (reactive oxygen species). Hence, investigating its potential as an effective antioxidant and its protective mechanisms against chronic ammonia stress in crucian carp is highly valuable. Experimental fish (initial weight 20.47 ± 1.68 g) were fed diets supplemented with or without 0.1% α-lipoic acid followed by a chronic ammonia exposure (10 mg/L) for 42 days. The results revealed that chronic ammonia stress affected growth (weight gain rate, specific growth rate, and feed conversion rate), leading to oxidative stress (decreased the activities of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase; decreased total antioxidant capacity), increased lipid peroxidation (accumulation of malondialdehyde), immune suppression (decreased contents of nonspecific immune enzymes AKP and ACP, 50% hemolytic complement, and decrease of immunoglobulin M), impaired ammonia metabolism (reduced contents of Glu, GS, GSH, and Gln), imbalance of expression of induced antioxidant-related genes (downregulation of Cu/Zu SOD, CAT, Nrf2, and HO-1; upregulation of GST and Keap1), induction of pro-apoptotic molecules (transcription of BAX, Caspase3, and Caspase9), downregulation of anti-apoptotic gene Bcl-2 expression, and induction of endoplasmic reticulum stress (upregulation of IRE1, PERK, and ATF6 expression). The results suggested that the supplementation of α-lipoic acid could effectively induce humoral immunity, alleviate oxidative stress injury and endoplasmic reticulum stress, and ultimately alleviate liver injury induced by ammonia poisoning (50–60% reduction). This provides theoretical basis for revealing the toxicity of long-term ammonia stress and provides new insights into the anti-ammonia toxicity mechanism of α-lipoic acid.

Three different natural antioxidants (tea polyphenol, ferulic acid, α-lipoic acid) and their mixture were estimated for the potential protective action on DNA damage. Antioxidant activity of the products was evaluated through protection against DNA damage induced by 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH). In this system, the mixture of tea polyphenol and ferulic acid showed maximum potential activity, while the α-lipoic acid alone was determined as the weakest antioxidant in gel electrophoresis assay. Results of this study demonstrated that tea polyphenol, ferulic acid and α-lipoic acid exhibited good synergistic effects, and all the mixtures were more resistant than any antioxidant alone. [ABSTRACT FROM AUTHOR]

Background and Aims: The aim of this study was to investigate the histological and biochemical effects of the antioxidant combination on liver tissue of streptozotocin (STZ)-induced diabetic mice. Methods: Five groups of mice were given a citrate buffer (CB), the antioxidant solvents (AS), the antioxidant combination (A) (α-lipoic acid, selenium, and vitamin E), STZ (D), the antioxidant combination and STZ (A+D). The mice were sacrificed, and their liver tissues were taken out. The liver tissues were examined histologically and immune+ cell numbers of cannabinoid receptors (CB1R and CB2R) were detected. Xanthine oxidase (XO) activity, glutathione (GSH) and lipid peroxidation (LPO) levels, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), γ-glutamyl transferase (GGT), paraoxonase (PON), glucose-6-phosphate dehydrogenase (G6PD) activities, protein carbonyl content (PCC) and advanced oxidation protein product (AOPP), sialic acid, fucose, hexose and hydroxyproline (OH-proline) levels were biochemically determined. Results: Certain degenerative changes were reduced in the A+D group compared histologically to the D group. There were no significant changes in the number of CB1R immune+ cells. The number of CB2R immune+ cells was significantly reduced in the D group compared to the CB group. The GSH level, CAT, SOD, GR, GPx, GST, PON, and G6PD activities were increased while XO and GGT activity, LPO, PCC, AOPP, hexose, fucose, sialic acid, and OH-proline level were biochemically decreased in the A+D group compared to the D group. Conclusion: The use of the antioxidant combination had a positive effect on the livers of diabetic mice with histochemical and biochemical changes, while there was no effect on the regulation of cannabinoid receptors expressions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Changes in hormone levels, improper lipid metabolism, and oxidative stress all significantly contribute to the pathogenic process of polycystic ovarian syndrome (PCOS). According to earlier research, pioglitazone and alpha-lipoic acid are crucial in the emergence of PCOS. The beneficial effects of pioglitazone and alpha-lipoic acid on PCOS were examined in the current study. PATIENTS AND METHODS: The 120 patients with PCOS received three months of treatment in pioglitazone groups (n=40 case, 30 mg/time, 1 time/day), α-lipoic acid (n=40 case, 0.6 g/time, 1 time/day), and combination therapy (n=40 case, pioglitazone 30 mg/time, 1 time/day and α-lipoic acid, 0.6 g/time, 1 time/day). Before and after therapy, the following factors were evaluated: the hormonal profile, fasting serum insulin, body weight, body mass index (BMI), menstruation status, oxidative stress, and indications of lipid metabolism. RESULTS: The combination of pioglitazone and α-lipoic acid has a significantly improving effect on BMI, body weight, oxidative stress levels, lipid metabolism, and menstrual status. A significant increase in body weight, BMI, and follicle-stimulating hormone (FSH) levels were found in mice after being treated with α-lipoic acid alone. However, the use pioglitazone alone improves body weight, BMI, the calculation of insulin resistance index (HOMA-IR), Area under the curve (AUC)-insulin, fasting glucose/insulin (G/I) ratio, total testosterone, and malondialdehyde (MDA) levels in post-treatment than pre-treatment. CONCLUSIONS: These findings suggest that pioglitazone alone has a better effect than alpha-lipoic acid in improving oxidative stress levels, BMI, and menstrual cyclicity. Additionally, treatment with pioglitazone and alpha-lipoic acid did demonstrate a greater effect than monotherapy with each medication alone. [ABSTRACT FROM AUTHOR]

Cancer has become an important cause of mortality and morbidity in the world. Over the past decades, biomedical research revealed insights into the molecular events and signaling pathways involved in carcinogenesis and cancer progression. Matrix metalloproteinases (MMPs) are a diverse family of enzymes that can degrade various components of the extracellular matrix and are considered as potential diagnostic and prognostic biomarkers for many cancer types and cancer stages. Recently, studies on the role of natural-origin active substances in the prevention of cancer development gained importance. Among them, the α-lipoic acid, which is commonly found in plants, displayed potent anti-proliferative effects on cancer cell lines. However, the effect of the compound on the induction of apoptosis and mRNA expression of MMPs in human prostate cancer cells remains unclear. The present study aimed to evaluate the anti-proliferative and apoptotic activity of α-lipoic acid in human PC3 prostate carcinoma cells considering different concentrations and exposure durations. The findings showed that, α-lipoic acid significantly decreased PC3 cell viability with an IC50 value of 1.71 mM at 48 h (p < 0.05). Additionally, the compound significantly increased Annexin-V binding in cells compared to control and induced a significant alteration in mitochondrial membrane potential and caspase levels (p < 0.05). Furhermore, the RT-PCR analyses have revealed that α-lipoic acid reduced MMP-9 mRNA expression in PC3 cells compared to the control (p < 0.05). In conclusion, this study highlights that α-lipoic acid induced apoptosis in human PC3 prostate cancer cells and inhibited the MMP-9 gene at the mRNA level, which is known to play a role in metastasis development. [ABSTRACT FROM AUTHOR]

Objectives: Acetaminophen (APAP)-induced nephrotoxicity is detrimental consequence for which there has not been a standardized therapeutic regimen. Although, N-acetylcysteine (NAC) is a well-known antidote used in APAP-induced hepatotoxicity, its benefit in nephrotoxicity caused by APAP is almost lacking. This study aimed to compare the possible protective effect of thymoquinone (TQ), curcumin (CR), and α-lipoic acid (α-LA), either in solo or in combination regimens with that of NAC against APAP-induced renal injury. Design and method: Rats were divided into nine groups; control group, APAP intoxicated group (1000 mg/kg; orally), and the remaining seven groups received, in addition to APAP, oral doses of NAC, TQ, CR, α-LA, CR plus TQ, TQ plus α-LA, or CR plus α-LA. The first dose of the aforementioned antioxidants was given 24 h before APAP, and then the second dose was given 2 h after APAP, whereas the last dose was given 10 h after administration of APAP. Results: Treatment with APAP elevated kidney markers like serum uric acid, urea, and creatinine. In addition, it increased the serum level of tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and thiobarbituric acid reactive species (TBARS). Also, the protein expression of renal janus kinase (JAK) and cyclooxygenase (COX)-2 were all upregulated by APAP. In contrast, the expression of Nrf2 and the renal levels of superoxide dismutase and glutathione were downregulated. Treatment with the indicated natural antioxidants resulted in amelioration of the aberrated parameters through exhibiting anti-inflammatory, antioxidant and free radical-scavenging effects with a variable degree. Conclusion: The combined administration of CR and TQ exerted the most potent protection against APAP-induced nephrotoxicity through its anti-inflammatory and free radical-scavenging effects (antioxidant) which were comparable to that of NAC-treatment.

Chronic COVID syndrome is characterized by chronic fatigue, myalgia, depression and sleep disturbances, similar to chronic fatigue syndrome (CFS) and fibromyalgia syndrome. Implementations of mitochondrial nutrients (MNs) with diet are important for the clinical effects antioxidant. We examined if use of an association of coenzyme Q10 and alpha lipoic acid (Requpero®) could reduce chronic covid symptoms. The Requpero study is a prospective observational study in which 174 patients, who had developed chronic-covid syndrome, were divided in two groups: The first one (116 patients) received coenzyme Q10 + alpha lipoic acid, and the second one (58 patients) did not receive any treatment. Primary outcome was reduction in Fatigue Severity Scale (FSS) in treatment group compared with control group. complete FSS response was reached most frequently in treatment group than in control group. A FSS complete response was reached in 62 (53.5%) patients in treatment group and in two (3.5%) patients in control group. A reduction in FSS core < 20% from baseline at T1 (non-response) was observed in 11 patients in the treatment group (9.5%) and in 15 patients in the control group (25.9%) (p < 0.0001). To date, this is the first study that tests the efficacy of coenzyme Q10 and alpha lipoic acid in chronic Covid syndrome. Primary and secondary outcomes were met. These results have to be confirmed through a double blind placebo controlled trial of longer duration. [ABSTRACT FROM AUTHOR]

With the rising demand for new cultivars of carnation, efficient transformation protocols are needed to enable the bioengineering of new traits. Here, we established a novel and efficient Agrobacterium-mediated transformation system using callus as the target explant for four commercial carnation cultivars. Leaf-derived calli of all cultivars were inoculated with Agrobacterium tumefaciens strain LBA4404 containing the plasmid pCAMBIA 2301 harboring genes for β-glucuronidase (uidA) and neomycin phosphotransferase (nptII). Polymerase chain reaction (PCR) and histochemical assays confirmed the presence of uidA and β-glucuronidase (GUS), respectively in transgenic shoots. The effect on transformation efficiency of medium composition and the presence of antioxidants during inoculation and co-cultivation was investigated. The transformation efficiency was increased in Murashige and Skoog (MS) medium lacking KNO3 and NH4NO3, and also in MS medium lacking macro and micro elements and Fe to 5% and 3.1% respectively, compared to 0.6% in full-strength medium. Transformation efficiency was increased dramatically to 24.4% across all carnation cultivars by the addition of 2 mg/l melatonin to nitrogen-depleted MS medium. Shoot regeneration was also doubled in this treatment. The establishment of this efficient and reliable transformation protocol can advance the development of novel carnation cultivars through molecular breeding approaches. Highlights: Melatonin at 2 mg/l substantially increases the Agrobacterium-mediated transformation efficiency of carnation cultivars to 24%. Nitrogen-depleted inoculation and co-cultivation media can greatly enhance carnation transformation. Callus is a potential target explant for Agrobacterium transformation of carnation. Melatonin and lipoic acid can considerably promote the shoot regeneration from transformed callus. The established protocol for carnation transformation is cultivar independent. [ABSTRACT FROM AUTHOR]