designed Alphz-lipoic experiments and analyzed xcid data. The dithiolane ring Alpha-lipoic acid and cellular regeneration accounted for the reactivity of Alphw-lipoic acid. NMR study Alpha-lipoic acid and cellular regeneration Anxiety self-help tools acid binding cellylar bovine serum albumin. After performing Shapiro—Wilk normality test, t test was used to compare the difference between ALA and vehicle. bibtex BibTex. Aging is also related to oxidative stress, which in turn leads to hastened cellular senescence and organ dysfunction. performed the core experiments and data analysis.

Alpha-lipoic acid and cellular regeneration -

Principal Investigator, Linus Pauling Institute Professor, Dept. of Biochemistry and Biophysics Helen P. Rumbel Professor for Healthy Aging Research Oregon State University.

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Sena CM, Cipriano MA, Botelho MF, Seica RM. Lipoic acid prevents high-fat diet-induced hepatic steatosis in Goto Kakizaki rats by reducing oxidative stress through Nrf2 activation.

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Utilization of the insulin-signaling network in the metabolic actions of alpha-lipoic acid-reduction or oxidation? Diesel B, Kulhanek-Heinze S, Holtje M, et al. Alpha-lipoic acid as a directly binding activator of the insulin receptor: protection from hepatocyte apoptosis.

Estrada DE, Ewart HS, Tsakiridis T, et al. Yaworsky K, Somwar R, Ramlal T, Tritschler HJ, Klip A. Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by alpha-lipoic acid in 3T3-L1 adipocytes.

Ying Z, Kampfrath T, Sun Q, Parthasarathy S, Rajagopalan S. Evidence that alpha-lipoic acid inhibits NF-kappaB activation independent of its antioxidant function. Inflamm Res. Smith AR, Hagen TM.

Vascular endothelial dysfunction in aging: loss of Akt-dependent endothelial nitric oxide synthase phosphorylation and partial restoration by R -alpha-lipoic acid. Biochem Soc Trans. Wang Y, Li X, Guo Y, Chan L, Guan X. alpha-Lipoic acid increases energy expenditure by enhancing adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice.

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Diabetes Res Clin Pract. Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials.

Roberts AC, Porter KE. Cellular and molecular mechanisms of endothelial dysfunction in diabetes. Diab Vasc Dis Res. Heitzer T, Finckh B, Albers S, Krohn K, Kohlschutter A, Meinertz T. Beneficial effects of alpha-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress.

Heinisch BB, Francesconi M, Mittermayer F, et al. Alpha-lipoic acid improves vascular endothelial function in patients with type 2 diabetes: a placebo-controlled randomized trial.

Eur J Clin Invest. Xiang G, Pu J, Yue L, Hou J, Sun H. alpha-lipoic acid can improve endothelial dysfunction in subjects with impaired fasting glucose. Xiang GD, Sun HL, Zhao LS, Hou J, Yue L, Xu L.

The antioxidant alpha-lipoic acid improves endothelial dysfunction induced by acute hyperglycaemia during OGTT in impaired glucose tolerance. Clin Endocrinol Oxf. Sola S, Mir MQ, Cheema FA, et al. Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction ISLAND study.

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Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial ALADIN III Study.

ALADIN III Study Group. Alpha-lipoic acid in diabetic neuropathy. Ziegler D, Ametov A, Barinov A, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Ziegler D, Low PA, Litchy WJ, et al. Efficacy and safety of antioxidant treatment with alpha-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial.

Ziegler D, Low PA, Freeman R, Tritschler H, Vinik AI. Predictors of improvement and progression of diabetic polyneuropathy following treatment with alpha-lipoic acid for 4 years in the NATHAN 1 trial. J Diabetes Complications. Balcioglu AS, Muderrisoglu H. Diabetes and cardiac autonomic neuropathy: Clinical manifestations, cardiovascular consequences, diagnosis and treatment.

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A 4-month randomized controlled multicenter trial DEKAN Study. Deutsche Kardiale Autonome Neuropathie. Nguyen N, Takemoto JK. A case for alpha-lipoic acid as an alternative treatment for diabetic polyneuropathy. J Pharm Pharm Sci. Diabetic Eye Disease. Gebka A, Serkies-Minuth E, Raczynska D.

Effect of the administration of alpha-lipoic acid on contrast sensitivity in patients with type 1 and type 2 diabetes. National Multiple Sclerosis Society. Definition of Multiple Sclerosis MS. Types of Multiple Sclerosis MS. Marracci GH, Jones RE, McKeon GP, Bourdette DN.

Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis. J Neuroimmunol. Morini M, Roccatagliata L, Dell'Eva R, et al.

Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis. Schreibelt G, Musters RJ, Reijerkerk A, et al. Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity.

J Immunol. Salinthone S, Schillace RV, Marracci GH, Bourdette DN, Carr DW. Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells. Schillace RV, Pisenti N, Pattamanuch N, et al.

Lipoic acid stimulates cAMP production in T lymphocytes and NK cells. Biochem Biophys Res Commun. George JD, Kim E, Spain R, Bourdette D, Salinthone S. Effects of lipoic acid on migration of human B cells and monocyte-enriched peripheral blood mononuclear cells in relapsing remitting multiple sclerosis.

Chaudhary P, Marracci GH, Bourdette DN. Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis.

Marracci GH, McKeon GP, Marquardt WE, Winter RW, Riscoe MK, Bourdette DN. Alpha lipoic acid inhibits human T-cell migration: implications for multiple sclerosis. J Neurosci Res. Yadav V, Marracci G, Lovera J, et al. Lipoic acid in multiple sclerosis: a pilot study.

Mult Scler. Yadav V, Marracci GH, Munar MY, et al. Pharmacokinetic study of lipoic acid in multiple sclerosis: comparing mice and human pharmacokinetic parameters.

Khalili M, Eghtesadi S, Mirshafiey A, et al. Effect of lipoic acid consumption on oxidative stress among multiple sclerosis patients: a randomized controlled clinical trial. Nutr Neurosci. Khalili M, Azimi A, Izadi V, et al. Does lipoic acid consumption affect the cytokine profile in multiple sclerosis patients: a double-blind, placebo-controlled, randomized clinical trial.

Khalili M, Soltani M, Moghadam SA, Dehghan P, Azimi A, Abbaszadeh O. Effect of alpha-lipoic acid on asymmetric dimethylarginine and disability in multiple sclerosis patients: A randomized clinical trial.

Electron Physician. Chronic kidney disease is a gradual loss of kidney function that leads to the accumulation of waste products in the blood. Diabetes and high blood pressure are two of the major risk factors for chronic kidney disease Granata et al.

In this condition, cellular metabolic changes occur that may lead to the major production of free radicals that play a crucial role in the development of renal damage and the onset of treatment resistance. Hypoxia, ROS, and oxidative stress may cause severe kidney injury and ischemic reperfusion injury Zhang and McCullough Patients suffering from end-stage renal disease and kept on hemodialysis have very high chances of cardiovascular mortality Levey et al.

Intravenous iron infusion has become an essential segment of anemia management in end-stage renal disease patients. Iron injection intake leads to oxidative stress in the patients Lim et al.

After administration of intravenous iron, oxidative stress markers formed, including lipid hydroperoxide, F2 isoprostane, and malondialdehyde, a reactive aldehyde that gives rise to toxic stress in cells Del et al. Research shows that after the administration of intravenous iron to chronic kidney disease and hemodialysis patients, malondialdehyde increases speedily Lim et al.

The generation of lipid hydroperoxide results in oxidative damage in lipoproteins, cell membranes, and other lipid-containing structures Girotti and Kriska The antioxidant activities of α-lipoic acid were better than N -acetylcysteine at curing oxidative stress, including diabetic neuropathy and glomerular injury.

α-Lipoic acid administration leads to a reduction in oxidative stress markers low-density lipoprotein oxidizability and plasma protein carbonyls ; thus, it is appreciable that administration of this agent may reduce oxidative stress induced by intravenous IV iron Marangon et al.

However, in diabetic nephropathy, TGFβ1 is related to MAPK and induces the production of fibronectin in mesangial cells.

α-Lipoic acid ameliorates the proteinuria by decreasing expressions of the TGFβ1 and fibronectin protein Lee et al. The patients with autosomal dominant polycystic kidney disease treated with α-lipoic acid showed a significant improvement in metabolic, inflammatory, and endothelial functions Lai et al.

As a short-chain fatty acid, α-lipoic acid is synthesized inside the human body to work as an antioxidant, safeguarding body cells from injury, and helping restore the scales of other antioxidants, like vitamins C and E Moura et al.

Several studies have shown that combining α-lipoic acid with fructose can reduce fructose-induced inflammation, hepatic oxidative stress, and insulin resistance. It is also found that α-lipoic acid can act as a chemopreventive agent because it inhibits the inflammation linked to carcinogenesis Moon α-Lipoic acid can reduce inflammatory markers in patients with heart disease, as oxidative stress is assumed to be the main cause of many cardiovascular diseases, together with hypertension, and heart failure.

Oxidative stress increases during the aging process, resulting in either enhanced ROS generation or diminished antioxidant safeguards.

Aging is also related to oxidative stress, which in turn leads to hastened cellular senescence and organ dysfunction. Antioxidants may assist in reducing the incidence of some pathologies of heart diseases and have anti-aging properties Wollin and Jones Several studies also show that infusion of irbesartan and α-lipoic acid to patients with the metabolic syndrome diminishes pro-inflammatory markers and enhances endothelial function, elements that are indicated in the pathogenesis of aterosclerosis Sola et al.

Along with that, it is found that α-lipoic acid can protect the liver from inflammatory disorders as well. Additionally, α-lipoic acid may help reduce the blood levels of several inflammatory markers, including IL-6 and ICAM-1 Liu et al.

Infertility is defined as the inability to conceive after engaging in regular sexual activity without using contraception for at least a year. Numerous medications have been utilized to improve sperm quality due to therapeutic limitations Dong et al. Male infertility is partially caused by anatomical anomalies such as ductal blockages, varicocele, and ejaculatory problems.

Depending on the kind and concentration of the ROS as well as the location and length of exposure to the ROS, sperm function may be positively or negatively impacted by ROS Thuwanut et al. According to studies, male germ cells can create ROS at different stages of their development.

Due to the depletion of intracellular ATP and the reduced phosphorylation of axonemal proteins, it has been discovered that somewhat elevated quantities of ROS have no effect on sperm survival but instead render them immobile Takei et al. Excessive hydrogen peroxide concentrations, a major ROS producer, also cause lipid peroxidation and cell death.

By reducing ROS generation, antioxidant medications maintain sperm viability and motility and can help safeguard sperm DNA integrity. Consuming dietary antioxidants may also improve semen conditions. It has been determined that male infertility is associated with a lower intake of specific antioxidant nutrients, such as vitamins A, C, and E, folate, zinc, carnitine, and selenium Buhling and Laakmann α-Lipoic acid is also a powerful antioxidant that helps in the regulation of ROS production.

α-Lipoic acid or its reduced form dihydrolipoic acid quenches several oxygen-free radical species in both aqueous and lipid phases Sacks et al. The available report suggests that α-lipoic acid could improve the sperm motility rate and reduce sperm DNA damage, thereby improving sperm quality Ibrahim et al.

Also, α-lipoic acid shows the positive effect in oocyte maturation, embryo development, and reproductive outcome Dong et al. Regular administration of α-lipoic acid reduces the pelvic pain in endometriosis and regularizes the menstrual blood flow.

α-Lipoic acid represents a promising new molecule for infertility and additional clinical studies are recommended in the future.

Cigarette smoking is a detrimental effect on the genital system of rat models due to oxidative stress. Smoking has a negative effect on the genital system via hypoxia-inducible factors HIF-1α and HIF-2α , TNF-α, caspase 3, and the calcitonin gene-related peptide CGRP in the uterus, and α-lipoic acid protected against the negative effects on the female reproductive system Asci et al.

α-Lipoic acid also promoted decreasing effects of nicotine-induced skin, lung, and liver damage Ateyya et al. Microorganisms are responsible for various types of skin- and gut-related disorders. The gradual enhancements in the rapidity of resistance to antibiotics turn to rise in oral pathologies.

α-Lipoic acid was found to inhibit the growth of various oral microorganisms to a large extent, such as Pseudomonas species, Escherichia coli , Staphylococcus aureus , and Candida albicans.

α-Lipoic acid can arrest the growth of Candida albicans thereby exhibiting antifungal activity which is directly proportional to its concentration Zhao et al.

α-Lipoic acid also arrests the growth of Cronobacter sakazakii strains with the minimum inhibitory concentration MIC in the range from 2. It was corroborated that α-lipoic acid shows antimicrobial potential for affecting the membrane integrity, causing dysfunction of the cell membrane and alterations in cellular morphology.

Recent studies also state that ALA is also effective against Rickettsia rickettsii , which is a constrained intracellular bacterium that generates Rocky Mountain spotted fever. α-Lipoic acid has significant ability to penetrate nucleus and affect intracellular actin-based mobility Eremeeva and Silverman ; Sahni et al.

α-Lipoic acid has the potential for protection against mycotoxin and treatment of mycotoxicosis Rogers Another report suggested that α-lipoic acid has protective efficacies against aflatoxin B1-induced oxidative damage in the liver Li et al.

The beneficial effect of α-lipoic acid combined with other antioxidants, such as epigallocatechin gallate, affects the life span and age-dependent behavior of the nematode Caenorhabditis elegans Phulara et al. In a nutshell, α-lipoic acid is an important molecule as antimicrobial, antifungal, antinematodal, and antiviral properties affecting multiple targets.

This combination affects the menstrual rate of women with PCOS positively, irrespective of their metabolic phenotype and with a higher dose of myo-inositol more evident and insulin-independent effect is seen de Cicco et al. D-Chiro-inositol and α-lipoic acid, in a combination treatment, may have a strong impact on metabolic profile in women with PCOS Cianci et al.

In PCOS, α-lipoic acid also decreases oxidative damage and insulin resistance. Endometriosis can be prevented and treated by a combination of N -acetyl cysteine, α-lipoic acid, and bromelain.

α-Lipoic acid supplementation in patients with a suspected miscarriage to improve subchorionic hematoma resorption is a promising field of investigation. In addition, α-lipoic acid could be used to prevent diabetic embryopathy and premature fetal membrane rupture caused by inflammation.

Finally, α-lipoic acid can be used safely to treat neuropathic pain and as a dietary supplement during pregnancy di Tucci et al. The severe acute respiratory syndrome coronavirus-2 SARS-CoV-2 epidemic COVID has emerged as a rapidly spreading communicable disease that currently affects all nations throughout the world.

Although the virus has been found in the stool and urine of infected people, the likelihood of alternative channels of transference cannot be ruled out. The sickness is primarily spread through large respiratory droplets Princess Diabetes patients are more likely to get an infection.

According to research, patients with the coronavirus that causes the severe acute respiratory syndrome SARS and pandemic influenza A were seen as having diabetes as a substantial risk factor for mortality with H1N1 influenza Yang et al.

Of people who died from COVID in Wuhan, China, According to a theory Sayıner and Serakıncı, , α-lipoic acid controls the immune system by controlling T-cell activation, making it a useful treatment candidate for the cytokine storm that causes SARS-CoV-2 infection.

According to studies, treating diabetic patients with α-lipoic acid will help them fight COVID Cure and Cure α-Lipoic acid is a short-chain fatty acids SCFAs derived from the fermentation of vegetables and meat and modulates the gut microbiota without reducing the microbial diversity Tripathi et al.

A recent study showed that α-lipoic acid and the SCFAs produced by Ruminococcaceae rejuvenated aged intestinal stem cells by preventing the age-associated endosome reduction Du et al.

α-Lipoic acid takes part in crucial biological operations, together with the fixation and modulation of mitochondrial multi-enzyme complexes, oxidation of amino acids and carbohydrates, removal of ROS, and harmonization of energetic metabolism Shay et al.

At a younger age, the human body can synthesize α-lipoic acid itself in the required amount, but its quantity remarkably decreases with age, which is supposed to be connected to age-related organic dysfunction Hagen et al.

Drosophila midgut is an appropriate prototype structure for the learning of mechanisms underlying the age-associated decline in stem cell function. A decrease in differentiation efficiency and a malignant increase in proliferation rate takes place in the intestinal stem cells inside the midguts of Drosophila when it ages.

Thus, the mRNA and protein expression of Las in Drosophila intestinal stem cells go through a significant depletion in response to aging, which in turn causes a curtailment of α-lipoic acid in midguts of aged flies.

α-Lipoic acid has so many molecular targets for disease management and biological action Fig. It doubles the levels of PPAR-mRNA and protein while decreasing the activation of the c-Jun N -terminal kinase JNK signaling pathway Rousseau et al.

α-Lipoic acid reduces endoplasmic reticulum stress and enhances glucose absorption by targeting the DNAJB3 DnaJ heat shock protein family and mRNA molecule Diane et al. According to reports, it lowers the NALP-3 inflammasome in the endometrium of women who experience idiopathic recurrent pregnancy loss Di et al.

By inhibiting breast cancer cell proliferation, cell cycle progression, and the epithelial-to-mesenchymal transition, α-lipoic acid has significant antiproliferative effects. By blocking the transforming growth factor beta TGFβ signaling pathway, α-lipoic acid prevents breast cancer cells from migrating and encroaching Tripathy et al.

Glucose fluctuations in diabetic encephalopathy encourage neuronal death. α-Lipoic acid has renoprotective effects on rat kidneys damage brought on by iron overload through inhibiting NADPH oxidase 4 and p38 MAPK signaling Cavdar et al. α-Lipoic acid diminishes the serum immunoglobulin E IgE levels of the atopic dermatitis mice model and enhances splenic B cell counts in endotoxemia mice which showed that IgE plays a modulating role in the expansion, death, and function of B-cells.

Recent studies show that α-lipoic acid enhances cAMP synthesis by activation of EP2 and EP4 prostaglandin receptors in peripheral blood T-cells. The enhanced level of cAMP inside cells reduces the expression of IL-2 and IL-2Rα CD25 that in turn influence expansion, death, and function of T-cells.

Natural killer NK cells have two main functions: cytotoxicity and interferon gamma IFN-γ secretion. IFN-γ is a powerful macrophage activator for both lysis and phagocytosis.

Although α-lipoic acid has long been discovered as an antioxidant, it has also been demonstrated to improve glucose and ascorbate treatment, activate phase II detoxification via the transcription factor Nrf2, increase eNOS activity, and lower expression of MMP-9 and VCAM-1 through repression of NF-κB.

α-Lipoic acid and its reduced form, dihydrolipoic acid, could be used for their chemical properties as a redox pair to modify protein conformations by forming mixed disulfides. Beneficial effects are accomplished with low micromolar levels of α-lipoic acid, suggesting that its therapeutic potential extents beyond the precise definition of an antioxidant agent.

α-Lipoic acid is a well-known antioxidant consumed to remedy a variety of disorders, though it is assumed a very secure supplement and intoxication is extremely infrequent, acute excessive-dose ingestions can cause mortality Emir et al. The safety of α-lipoic acid can be evaluated using sub-chronic and acute toxicity studies.

Studies have estimated an adult dose of α-lipoic acid up to mg with no severe side effects; however, excessive dose of α-lipoic acid is not suggested as it does not add any other therapeutic or nutritional advantage Cremer et al.

Furthermore, studies associated with α-lipoic acid conducted on primates displayed that more lethal dose would lead to hepatic necrosis, indicating that excess doses of intravenous α-lipoic acid can be able to produce resistance Vigil et al.

α-Lipoic acid has also been shown to reverse the adverse health effects of mycotoxins Rogers Skin and gastrointestinal disorders are the most frequently reported adverse effects for α-lipoic acid-containing dietary supplements Gatti et al.

Allergic reactions like rashes, hives, and itching are the side effects of the oral intake of α-lipoic acid. However, effects like vertigo, diarrhea, and vomiting are dose dependent. It is suggested that the use of α-lipoic acid should be discouraged immediately if any allergic reaction occurs Ziegler et al.

α-Lipoic acid is used either as an excipient or as a main therapeutic ingredient in various types of nanoformulations size of about 1— nm ; due to this small size, it has a very large surface area and hence high area of contact which enhances the therapeutic effect of drug particle incorporated Jong and Borm It can be formulated in the form of nanostructure lipid carriers, solid lipid nanoparticles, and nano-emulsion.

Silver nanoparticles AgNPs are extensively considered for their broad-spectrum antimicrobial outcome and can be employed instantly in biomaterials; however, the cellular protection of specific AgNP formulations should be profiled earlier for clinical utilization.

AgNPs can be able to outcome the evocation of oxidative harm and inflammatory lesions in human gingival fibroblast cells Jin et al. AgNPs capped with α-lipoic acid decrease toxicity as compared to other capping agents Verma et al.

Studies show that α-lipoic acid-capped AgNPs possess antimicrobial effects at low concentrations 2. Docetaxel, acytotoxic taxane diterpenoid sold under the brand name taxotere, is an antimicrotubule agent effective as chemotherapy medication to treat several types of cancer, including metastatic breast cancer Lyseng-Williamson and Fenton Co-delivery of docetaxel and α-lipoic acid using solid lipid nanoparticles SLNs as a carrier demonstrated remarkably higher uptake efficiency along with better cytotoxic and apoptotic capability and assured a better treatment of breast cancer Kothari et al.

The anti-inflammatory, antioxidant, and anti-apoptotic actions of α-lipoic acid, as well as the effectiveness of the encapsulation approach, can boost the efficiency and stability of α-lipoic acid, and reduce the neurotoxicity caused by AlCl3.

Furthermore, α-lipoic acid-SLNs outperform α-lipoic acid-chitosan nanoparticles Metwaly et al. HOMO—LUMO plots of the two enantiomers of α-lipoic acid a S -enantiomer; b R -enantiomer.

The biological roles of α-lipoic acid are highly varied, as this review has shown. In fact, as a bioactive agent, we are aware of only a few substances that act as diverse as α-lipoic acid.

Determining the specific cause-and-effect relationship between α-lipoic acid and its cellular targets will therefore be crucial. Whether α-lipoic acid directly controls the hormonal signals that trigger subsequent pharmacological effects on target organs is a subject that needs more investigation.

In this way, α-lipoic acid strengthens learning and short-term memory in aged rodents and encourages an anorectic effect in rodents that is AMPK-dependent Shay et al. Given that α-lipoic acid is almost entirely absorbed from the human gastrointestinal tract, metabolized, and excreted, negligible free α-lipoic acid is retained in tissues.

As recently established in mice, rats, and dogs, different β-oxidation and mono- and bis- S -methylation products of the sulfydryl groups appear to be implicated in urine metabolic patterns Fig.

Additionally, biliary elimination should be the focus of future research on the human metabolism of α-lipoic acid Teichert et al. Many studies have reported on the pleiotropic and medicinal activities of α-lipoic acid since its discovery in , followed by isolation and synthesis in the s Gomes and Negrato A molecular and electronic structure study of α-lipoic acid suggests that its antioxidant potential is responsible for its anti-disease activities.

However, preclinical and clinical studies form the foundation of much of the discussion presented here. As a result, α-lipoic acid has powerful anti-disease properties, such as those against cancer, metabolic syndrome, and inflammatory diseases. Several potential molecular targets have been investigated in relation to a variety of diseases.

The capacity of this substance to neutralize ROS, lessen oxidative stress, and trigger apoptosis is the fundamental mechanism underlying its effectiveness against various diseases and chronic disorders.

In all the clinical trials that were conducted with α-lipoic acid, it was either used alone or in conjunction with other medications. The safe dose for action was reported to be between and mg per day for the term stated for each illness condition. In the context of COVID, it is also hypothesized as a repurposed drug to investigate the inhibitory action on new molecular targets.

However, it is important to design computational studies and in vitro and in vivo investigations to offer comprehensive proof. Based on the information presented here, α-lipoic acid is useful in the treatment of reproductive diseases, which has been briefly explored in the context of polycystic ovary syndrome.

Despite all these reports and multiple clinical trials, it has not yet been approved for use in humans. Although its bioavailability is increased in the form of nanoformulations, α-lipoic acid changes the metabolism and bioavailability of co-administered medicines when taken in combination.

Despite there being few active clinical trials, this chemical is the subject of an increasing number of publications. As new information about the health benefits of α-lipoic acid will be gathered, its use in the clinic is more likely to be widely accepted. NeuroReport — Article CAS PubMed Google Scholar.

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Biochimie —

Lipoic regdneration often called α-lipoic acidalso known as thioctic cellulra, is a naturally occurring aci compound that is synthesized by plants and animals, Alpha-lipoic acid and cellular regeneration humans 1, 2. Alpha-lipoic acid and cellular regeneration acid Alpha-ljpoic covalently bound reheneration certain proteins Alhpa-lipoic, which function as part clelular essential caid multi enzyme Detoxification involved in energy and amino acid metabolism Alpha-lipoic acid and cellular regeneration Biological Activities. In addition to the physiological functions of protein-bound lipoic acid, there is increasing scientific and medical interest in potential therapeutic uses of pharmacological doses of free unbound lipoic acid 3. Lipoic acid contains two thiol sulfur groups, which may be oxidized or reduced ; dihydrolipoic acid is the reduced form of lipoic acid Figure 1 4. Lipoic acid also contains an asymmetric carbon, which means that lipoic acid can exist as one of two possible optical isomersalso called enantiomers. These enantiomers are mirror images of each other: R -lipoic acid and S -lipoic acid Figure 1. Only the R -enantiomer is endogenously synthesized and covalently bound to protein. Antagonism of ROS signaling can inhibit cell regenefation and autophagy, thus degeneration the maintenance and Chitosan for respiratory health of hematopoietic stem cells. Alpha lipoic acid ALA reggeneration, a small antioxidant molecule, affects cell apoptosis Outdoor strength training lowering regeberation ROS level. Transcriptome Alpha-lipoic acid and cellular regeneration Alphal-ipoic hPSCs regendration hemogenic endothelial cells showed that ALA promoted endothelial-to-hematopoietic transition by up-regulating RUNX1GFI1GFI1BMEIS2and HIF1A and down-regulating SOX17TGFB1TGFB2TGFB3TGFBR1and TGFBR2. ALA also up-regulated sensor genes of ROS signals, including HIF1AFOXO1FOXO3ATMPETENSIRT1and SIRT3during the process of hPSCs derived hemogenic endothelial cells generation. Furthermore, addition of ALA in ex vivo culture greatly improved the maintenance of functional cord blood HSCs by in vivo transplantation assay. Thus, ALA can be used in the study of hPSCs derived HSCs.

Lipoic Lower cholesterol with plant-based diet often called α-lipoic acidalso known as thioctic Alpna-lipoic, is a Alpha-kipoic occurring refeneration compound that is synthesized by plants regneeration animals, including humans 1, 2.

Lipoic acid is Alpha-pipoic bound regeneratino certain proteinswhich function as part of A,pha-lipoic mitochondrial multi enzyme Nutritious breakfast choices involved in energy and amino acid metabolism see Biological Activities.

In addition to the physiological functions of Alpha-li;oic lipoic acid, there is increasing scientific and medical interest in potential therapeutic uses of pharmacological acjd of free unbound lipoic acid 3. Aacid acid contains two thiol regeneratioon groups, cellullar may be oxidized or Alpha-lipoiv ; dihydrolipoic Recovery for individuals with co-occurring disorders is the reduced form of lipoic acid Figure 1 4.

Lipoic acid also contains an asymmetric carbon, which means that lipoic acid can exist as one of two possible regenerxtion isomersalso called Alpba-lipoic. These enantiomers are mirror images of Alpha-lipoic acid and cellular regeneration other: R -lipoic acid and Alpha-lipoic acid and cellular regeneration -lipoic acid Figure 1.

Only the R -enantiomer is endogenously synthesized regeneartion covalently celular to protein. R -lipoic acid Alpha-lipoic acid and cellular regeneration naturally in food see Muscle definition techniques sources.

Free ceplular lipoic an supplements Lentils and lentil salad dressing contain either R -lipoic acid or a racemic mixture of R -lipoic acid and S -lipoic acid regeneation Supplements. The synthesis of lipoic acid regenerxtion been Alpha-lopoic in Martial arts recovery drinks in the Herbal remedies for anxiety and stress Saccharomyces cerevisiaebut not all genes involved in the process have been identified celluular humans 5.

Lipoic acid is synthesized de Green tea brewing in mitochondria from octanoic acid, an regenwration fatty acid Cbound to the acyl-carrier protein ACP; see article on Pantothenic Acid during the process of fatty acid synthesis Figure 2.

An enzyme called lipoyl octanoyl transferase 2 catalyzes the transfer of the octanoyl Sharing Berry Recipes from octanoyl-ACP to Alph-lipoic conserved lysine of the Pre-game nutrition tips protein of Boost insulin sensitivity glycine cleavage system see also Biological Activities.

The next reaction cellulqr the cellulxr of two sulfur cellulad at positions 6 and 8 of Alpha-pipoic protein H-bound octanoyl moiety, thereby producing a dihydrolipoyl moiety. This step is catalyzed by the lipoic acid synthetase also called xnd synthasean enzyme reeneration iron-sulfur clusters that act as sulfur Virtual power recharge in the reaction 5.

Finally, Boosts digestive enzyme function enzyme celoular transferase 1 cellulsr the transfer of the dihydrolipoyl Alpha-pipoic from cellulr H protein of the glycine cleavage system to conserved lysine regeneratoin of the E2 components High-quality herbal extracts the α-ketoacid dehydrogenase multienzyme complexes 5.

The cellulsr of the dihydrolipoyl moiety is catalyzed by a dihydrolipoamide dehydrogenase Figure 2. Consumption of lipoic acid from Alpna-lipoic has not yet been found to result in Caffeine and muscle soreness increases of free lipoic Alppha-lipoic in human plasma or cells 36.

A liquid formulation of R -lipoic acid was found to celular better absorbed and more stable in the plasma, suggesting that it might be more efficacious than the aciid form in the management of a condition Hydration for hikers diabetic neuropathy 9, There may also be differences in bioavailability ane the two isomers of lipoic cellklar.

Yet, following oral ingestion, both ce,lular are cellullar metabolized and excreted. Plasma lipoic acod concentrations generally peak within Alpha-lipoic acid and cellular regeneration hour or less regneeration decline rapidly regenerafion, 711, In cells, lipoic acid is swiftly reduced to dihydrolipoic acid, and in vitro studies indicate that dihydrolipoic acid is rrgeneration rapidly axid from cells 3.

Moreover, a rgeneration study in 19 healthy adults suggested that the bioavailability of R, S -lipoic acid and R -lipoic acid regenfration vary with age and gender Finally, there is no evidence in humans that Alpha-lipoic acid and cellular regeneration lipoic acid can be 'activated' with ATP or GTP and incorporated into lipoic acid-dependent Alpha-lipolc by a Detoxification and stress relief transferase As Alpha-lipoic acid and cellular regeneration consequence, a loss of cellulra acid-dependent enzymatic activity caused by defects Alpha-lopoic endogenous lipoic Alpha-lipojc synthesis see Deficiency cannot be rescued by the provision of exogenous lipoic acid 5.

R regeeneration acid aicd an essential cofactor for several mitochondrial multi enzyme complexes that Blood sugar tracking critical reactions related to the catabolism vellular of amino acids and the production of energy Joint mobility support -lipoic acid is covalently bound to Alphx-lipoic specific lysine residue in at least one of Liver detox symptoms proteins in each Heavenly Orange Aroma complex.

Such a Alpha-lipoic acid and cellular regeneration protein regeneartion is known regenerstion a "prosthetic Alpha-lipooic. R -lipoic acid functions as a prosthetic group for the biological activity Alpha-lipooic the Sesame seed recipes multienzyme Strength training supplements. i the Alphaa-lipoic dehydrogenase complex that catalyzes the Daily blood sugar management of pyruvate to acetyl-coenzyme A Celllularan important substrate for energy production via the citric acid cycle.

Alpha-lipooc the α-ketoglutarate dehydrogenase complex that catalyzes the conversion of α-ketoglutarate to succinyl CoA, another important intermediate of the citric acid cycle. iii the Allpha-lipoic α-ketoacid dehydrogenase complex that is involved in the decarboxylation Breakfast schedule ketoacids in the catabolic pathway of the branched-chain amino acids, Aplha-lipoic leucine, Alpha-lipooc, and valine.

iv Alpha-lipooic 2-oxoadipate dehydrogenase complex that catalyzes the decarboxylation of 2-oxoadipate to glutaryl-CoA in the catabolic pathway of ergeneration, hydroxylysine, and tryptophan. All four α-ketoacid dehydrogenase complexes contain regeneratlon enzymatic activities, namely E1, E2, Alpha-lipoic acid and cellular regeneration, Hydration for young athletes during training E3.

Alpha-lkpoic is a regwneration pyrophosphate TPP celpular α-ketoacid dehydrogenase, R -lipoic acid functions as a prosthetic group essential for E2 transacetylase activity, and E3 is a flavin adenine dinucleotide FAD -dependent dihydrolipoamide dehydrogenase Figure 4. R -lipoic acid is also found in the E3-binding protein protein X component of the pyruvate dehydrogenase complex 5.

When considering the biological activities of supplemental unbound lipoic acid, it is important to keep in mind the limited and transient nature of the increases in plasma and tissue lipoic acid see Metabolism and Bioavailability 3. Scavenging reactive oxygen and nitrogen species : Reactive oxygen species ROS and reactive nitrogen species RNS are highly reactive compounds with the potential to damage DNAproteinsand lipids in cell membranes.

Both lipoic acid and dihydrolipoic acid can directly scavenge neutralize physiologically relevant ROS and RNS in the test tube reviewed in 3. However, whether direct quenching reactions occur in vivo is unknown.

The highest tissue concentrations of free lipoic acid likely to be achieved through oral supplementation are at least 10 times lower than those of other intracellular antioxidantssuch as vitamin C and glutathione. Moreover, free lipoic acid is rapidly eliminated from cells, so any increases in direct radical scavenging activity are unlikely to be sustained.

Regeneration of other antioxidants : When an antioxidant scavenges a free radicalit becomes oxidized itself and is not able to scavenge additional ROS or RNS until it has been reduced. In the test tube, dihydrolipoic acid is a potent reducing agent with the capacity to reduce the oxidized forms of several important antioxidants, including coenzyme Q 10vitamin Cand glutathione Figure 5 16, Dihydrolipoic acid may also reduce the oxidized form of α-tocopherol vitamin E directly or indirectly through regenerating oxidized vitamin C see the article on Vitamin E 18 or oxidized coenzyme Q 10 see the article on Coenzyme Q 10 Whether dihydrolipoic acid effectively regenerates antioxidants under physiological conditions is unclear 3.

Metal chelation : Redox -active metal ionssuch as free iron and coppercan induce oxidative damage by catalyzing reactions that generate highly reactive free radicals Compounds that chelate free metal ions in a way that prevents them from generating free radicals offer promise in the treatment of neurodegenerative diseases and other chronic diseases in which metal-induced oxidative damage may play a pathogenic role Both lipoic acid and dihydrolipoic acid have been found to inhibit copper- and iron-mediated oxidative damage in the test tube 22, 23 and to inhibit excess iron and copper accumulation in animal models 24, Lipoic acid may also be helpful as an adjunct treatment against heavy metal toxicity.

No clinical trial has examined the use of lipoic acid as a chelating agent in mercury toxicity, yet it has proven to be effective in several mammalian species 26, Activation of antioxidant signaling pathways: Glutathione is an important intracellular antioxidant that also plays a role in the detoxification and elimination of potential carcinogens and toxins.

Reductions in glutathione synthesis and tissue glutathione concentrations in aged animals compared to younger ones are suggestive of a potentially lower ability to respond to oxidative stress or toxin exposure Lipoic acid has been found to increase glutathione concentrations in cultured cells and in the tissues of aged animals fed lipoic acid 29, Lipoic acid might be able to increase glutathione synthesis in aged rats by up-regulating the expression of γ-glutamylcysteine ligase γ-GCLthe rate-limiting enzyme in glutathione synthesis 31and by increasing cellular uptake of cysteine, an amino acid required for glutathione synthesis Lipoic acid was found to upregulate the expression of γ-GCL and other antioxidant enzymes via the activation of the nuclear factor E2-related factor 2 Nrf2 -dependent pathway 31 Briefly, Nrf2 is a transcription factor that is bound to the protein Kelch-like ECH-associated protein 1 Keap1 in the cytosol.

Keap1 responds to oxidative stress signals by freeing Nrf2. Upon release, Nrf2 translocates to the nucleus where it can bind to the antioxidant response element ARE located in the promoter region of genes coding for antioxidant enzymes and scavengers.

Lipoic acid — but not dihydrolipoic acid — can react with specific sulfhydryl residues of Keap1, causing the release of Nrf2 For example, the upregulation of the Nrf2 pathway by lipoic acid in cultured hepatocytes and in the liver of obese or diabetic rats prevented lipid overload-induced steatosis 35 and cell death Lipoic acid also protected liver from oxidative stress-induced liver injury in methotrexate-treated rats through the activation of Nrf-2 pathway and other anti-inflammatory pathways Pre-treatment and post-treatment with lipoic acid, respectively, prevented and reversed lipopolysaccharide LPS -induced lung histopathological alterations in rats through Nrf2-mediated HO-1 upregulation Inhibition of nicotinamide adenine dinucleotide phosphate NADPH oxidase NOX : NOX is a plasma membrane-bound enzymatic complex that catalyzes the production of superoxide from oxygen and NADPH and has been involved in innate immune defense against microbes Treatment of gastric cancer cells with lipoic acid limited NOX-generated ROS production and reduced cancer cell proliferation induced by Helicobacter pylori H.

pylori infection The binding of insulin to the insulin receptor stimulates a cascade of protein phosphorylations leading to the translocation of glucose transporters GLUT4 to the cell membrane and an increased cellular uptake of glucose 3 Lipoic acid has been found to activate the insulin signaling cascade in cultured cells 342, 43increase GLUT4 translocation to cell membranes, and increase glucose uptake in cultured adipose and muscle cells 44, A computer modeling study suggested that lipoic acid might bind to the intracellular tyrosine kinase domain of the insulin receptor and stabilize the active form of the enzyme In addition to Nrf2 and insulin signaling pathways, lipoic acid was found to target other cell-signaling molecules thereby affecting a variety of cellular processes, including metabolismstress responses, proliferationand survival.

For example, in cultured endothelial cells, lipoic acid was found to inhibit IKK-β, an enzyme that promotes the translocation of redox -sensitive and pro-inflammatory transcription factornuclear factor-kappa B NFκB from the cytosol to the nucleus Additionally, lipoic acid increased mitochondrial biogenesis through triggering AMP -activated protein kinase AMPK -induced transcription factor PGC-1α activation in skeletal muscle of aged mice Several reviews of the literature have described pathways that are potential targets of lipoic acid in various models and under different experimental conditions Lipoic acid deficiency has been described in rare cases of inherited mutations in the lipoic acid biosynthetic pathway.

Mutations identified in patients with defective lipoic acid metabolism affect genes involved in the synthesis of iron-sulfur clusters and genes coding for lipoic acid synthetase LIASlipoyl transferase 1 LIPT1and dihydrolipoamide dehydrogenase E3 component of α-ketoacid dehydrogenase complexes; DLD 553, Chronically elevated blood glucose concentration is the hallmark of diabetes mellitus.

Type 1 diabetes is caused by the autoimmune destruction of the insulin -producing β-cells of the pancreasleading to an insufficient production of insulin.

Exogenous insulin is required to maintain a normal blood glucose concentration i. In contrast, impaired tissue glucose uptake in response to insulin a phenomenon called insulin resistance plays a key role in the development of type 2 diabetes Although patients with type 2 diabetes may eventually require insulin, interventions that enhance insulin sensitivity may be used to maintain normal blood glucose concentrations.

The term 'prediabetes' is sometimes used to describe early metabolic abnormalities that place individuals at high risk of developing type 2 diabetes. Of note, these patients are also at high risk for cardiovascular disease.

The effect of high-dose lipoic acid on glucose utilization has been primarily examined in individuals with type 2 diabetes. An early clinical trial in 13 patients with type 2 diabetes found that a single intravenous infusion of 1, mg of lipoic acid improved insulin -stimulated glucose disposal i.

A systematic review and meta-analysis identified 20 randomized controlled trials published between and that examined the effect of supplemental lipoic acid on markers of glucose utilization in 1, subjects with metabolic disorders not limited to type 2 diabetes The inner lining of blood vessels, known as the vascular endotheliumplays an important role in the maintenance of cardiovascular health.

In particular, nitric oxide NO regulates vascular tone and blood flow by promoting the relaxation of all types of blood vessels, including arteries — a phenomenon called vasodilation. Alterations in NO-mediated endothelium-dependent vasodilation results in widespread vasoconstriction and coagulation abnormalities and is considered to be an early step in the development of atherosclerosis.

The presence of chronic hyperglycemiainsulin resistanceoxidative stressand pro-inflammatory mechanisms contribute to endothelial dysfunction in patients with diabetes mellitus The measurement of brachial flow-mediated dilation FMD is often used as a surrogate marker of endothelial function.

Two techniques are being used to measure endothelium-dependent vasodilation. One technique measures the forearm blood flow by venous occlusion plethysmography during infusion of acetylcholine. Using this invasive technique, intra-arterial infusion of lipoic acid was found to improve endothelium-dependent vasodilation in 39 subjects with type 2 diabetes but not in 11 healthy controls A more recent randomizeddouble-blindplacebo -controlled study in 30 patients with type 2 diabetes found that intravenous infusion of mg of lipoic acid improved the response to the endothelium-dependent vasodilator acetylcholine but not to the endothelium-independent vasodilator, glycerol trinitrate Another noninvasive technique using ultrasound to measure flow-mediated vasodilation was used in two additional studies conducted by Xiang et al.

The results of these randomized, placebo-controlled studies showed that intravenous lipoic acid could improve endothelial function in patients with impaired fasting glucose 64 or impaired glucose tolerance Peripheral neuropathy is also a leading cause of lower limb amputation in diabetic patients Several mechanisms have been proposed to explain chronic hyperglycemia -induced nerve damage, such as intracellular accumulation of sorbitol, glycation reactions, and oxidative and nitrosative stress reviewed in The results of several large randomized controlled trials indicated that maintaining blood glucose at near normal concentrations was the most important step in limiting the risk of diabetic neuropathy and lower extremity amputation

: Alpha-lipoic acid and cellular regeneration

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We would like to thank Dr. Paul Thornalley for his critical reading of the manuscript and his constant support. We also thank Drs. Ziyad Abusara and Gerald Pfister for their technical help. This work was supported by Qatar Biomedical Research Institute, Hamad Bin Khalifa University intramural grant IGP to MD. Diabetes Research Center, Qatar Biomedical Research Institute QBRI , Hamad Bin Khalifa University HBKU , Qatar Foundation QF , Doha, Qatar. Abdoulaye Diane, Naela Mahmoud, Ilham Bensmail, Namat Khattab, Hanan A. College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar. You can also search for this author in PubMed Google Scholar. and N. performed the experiments. and M. designed the experiments and analyzed the data. wrote the manuscript. is the guarantor of this work. Correspondence to Mohammed Dehbi. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and permissions. Diane, A. Alpha lipoic acid attenuates ER stress and improves glucose uptake through DNAJB3 cochaperone. Sci Rep 10 , Download citation. Received : 10 January Accepted : 26 October Published : 24 November Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Revista Brasileira de Farmacognosia By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Skip to main content Thank you for visiting nature. nature scientific reports articles article. Download PDF. Subjects RNA RNA editing. Abstract Persistent ER stress, mitochondrial dysfunction and failure of the heat shock response HSR are fundamental hallmarks of insulin resistance IR ; one of the early core metabolic aberrations that leads to type 2 diabetes T2D. Introduction Increased insulin resistance IR in peripheral organs and progressive decline in β-cell function are the two early and crucial pathophysiological aberrations leading to chronic hyperglycemia and overt type 2 diabetes T2D. Materials and methods Reagents Anti-DNAJB3 antibody was purchased from Proteintech Proteintech Group, Inc. Table 1 List of siRNAs and sequences. Full size table. Table 2 Primer list and sequences. Results ALA induces the endogenous expression of DNAJB3 It has been shown previously that ALA mediates its beneficial effects by activating the HSR. Figure 1. Full size image. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Discussion Impaired expression of HSP25, HSP72 and DNAJB3; three important components of the HSR has been reported to negatively correlate with the degree of IR 28 , 44 , References DeFronzo, R. Article PubMed Google Scholar Upadhyay, J. Article PubMed Google Scholar Wellen, K. Article CAS PubMed PubMed Central Google Scholar Engin, F. Article CAS PubMed Google Scholar Hotamisligil, G. Article ADS CAS PubMed Google Scholar Houstis, N. Article ADS CAS PubMed Google Scholar Szendroedi, J. Article CAS PubMed Google Scholar Rogers, R. 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Data in the bar graphs in B and D—F are presented as the mean ± sd. The results showed that ALA significantly up-regulated the protein expression of both HIF1A Fig. In short, the decreasing of ROS up-regulated HIF1A and P53 to inhibit cell cycle and cell apoptosis. The results indicated that there were scarcely human blood cells were detected in the peripheral blood of NSG mice data do not show. The results indicated that ALA significantly inhibited the cell cycle progress Supplementary Fig. S4A and B and reduced ROS level Supplementary Fig. Sequentially, we used CFU assay and in vivo transplantation system to assay the effect of ALA exerting on HSCs Fig. We isolated the nucleated cells from cord blood and then cultured for 7 days using SFEMII culture medium with ALA treatment or not. CFU assay was performed to reveal the differentiation potential of Ctrl or ALA-treated cultures. At the same time, the components of hematopoietic stem or progenitor cells were analyzed by flow cytometry. We conducted flow cytometry to analysis the chimerism of human blood cells in the recipient mice peripheral blood at 3 months post transplantation. The results indicated that ALA-treated cultures contributed significantly higher percentages of chimerism in mice peripheral blood compared to Ctrl cultures 1. However, based on the effects that ALA affects the cell proliferation and ROS level of hematopoietic stem and progenitor cells Supplementary Fig. All these results suggested that ALA can maintains HSCs function partially through inhibiting cell cycle and decreasing ROS level in ex vivo culture. ALA maintained functional HSC in ex vivo culture. A Strategy of analysis the effect of ALA exerted on HSC. B CFU assay of Ctrl or ALA-treated cultures with 7 days ex vivo culture. Total nucleated cells of cord blood were used as input cells for ex vivo culture. Five hundred total cells derived from Ctrl or ALA-treated cultures were used for CFU assay, and absolute colony numbers were counted on day E Representative flow cytometry plots of human blood cells chimerism at 3 months post-transplantation. Fresh cord blood nucleated cells, Ctrl cultures, and ALA-treated cultures were transplanted into 1. F Statistic analysis the percentages of donor derived cells at 3 months post-transplantation. Each point indicates an individual recipient. The data in the bar graphs in B, D , and F are presented as the mean ± sd. In this study, we used an in vitro coculture system to provide a new insight into the effects of ALA on hPSCs hematopoiesis. At early coculture stages, a high proportion of hemogenic endothelium cells with a low level of ROS was observed in ALA-treated cocultures, suggesting that ALA may promote development of hemogenic endothelium cells by modulating the ROS level. Transcriptome analysis of hemogenic endothelium cells indicated that ALA up-regulates genes promoting hematopoietic commitment, such as RUNX1 , GFI1 , GFI1B , MEIS2 , and HOXA9 , 43 , 45 , 47 and down-regulates signals in TGFβ pathways that negatively regulate endothelial-to-hematopoietic transition. Among ALA up-regulated transcription factors, HIF1A , RUNX1 , GFI1 , GFI1B , and HOXA9 are crucial factors involved in modulating hemogenic endothelial cells development. As reported previously, HIF1A acts as an upstream regulator of RUNX1 and NOTCH signaling, 46 and GFI1 and GFI1B act as downstream targets of RUNX1. ALA also significantly up-regulated the protein expression of both HIF1A Fig. In short, ALA decreased of ROS to up-regulated HIF1A and up-regulated P53 to inhibit cell cycle and cell apoptosis. Throughout the current study, we showed the role of ALA of affecting hematopoietic development or function by regulating ROS. The effect of ALA exerted on hematopoietic differentiation of human embryonic stem cells in three stages. This observation is reminiscent of a previous report showing that modulation of ROS signaling affects development of primitive hematopoietic progenitors from hPSCs. Particularly, ALA treatment allows observation of the mechanism by which ROS signals control early events during developmental hematopoiesis from hPSCs, which can never be mimicked using adult-type HSCs. Thus, ALA treatment might have the potential use in promoting in vitro expansion and maintenance of adult HSCs for clinical transplantation. Subsequently, both ex vivo and in vivo experiments were performed to assay the effect of ALA exerted on human cord blood HSCs. These results confirmed that ALA efficiently maintained functional HSCs in ex vivo culture. In summary, ALA could be added to hematopoietic differentiation systems to study development of HSCs from hPSCs. and J. performed the core experiments and data analysis. performed some of the experiments. and F. designed the project, discussed the data, and wrote the manuscript. approved the manuscript. contributed equally to this study. This research was supported by the China Postdoctoral Fund Program Grand M and the CAMS Initiatives for Innovative Medicine I2M, I2M, I2M Wielockx B , Grinenko T , Mirtschink P , et al. Hypoxia pathway proteins in normal and malignant hematopoiesis. Crossref Search ADS. Google Scholar. Shao L , Li H , Pazhanisamy SK , et al. Reactive oxygen species and hematopoietic stem cell senescence. Int J Hematol. Rehn M , Olsson A , Reckzeh K , et al. Hypoxic induction of vascular endothelial growth factor regulates murine hematopoietic stem cell function in the low-oxygenic niche. Tan DQ , Suda T. 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Lie ALM , Marinopoulou E , Lilly AJ , et al. Regulation of RUNX1 dosage is crucial for efficient blood formation from hemogenic endothelium. Lancrin C , Mazan M , Stefanska M , et al. GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment. Gerri C , Marass M , Rossi A , et al. Hif-1alpha and Hif-2alpha regulate hemogenic endothelium and hematopoietic stem cell formation in zebrafish. MEIS2 regulates endothelial to hematopoietic transition of human embryonic stem cells by targeting TAL1. Stem Cell Res Ther. Teichweyde N , Horn PA , Klump H. HOXB4 increases runx1 expression to promote the de novo formation of multipotent hematopoietic cells. Transfus Med Hemother. Teichweyde N , Kasperidus L , Carotta S , et al. HOXB4 promotes hemogenic endothelium formation without perturbing endothelial cell development. Lilly AJ , Costa G , Largeot A , et al. Interplay between SOX7 and RUNX1 regulates hemogenic endothelial fate in the yolk sac. Lizama CO , Hawkins JS , Schmitt CE , et al. Repression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition. Nat Commun. Vargel O , Zhang Y , Kosim K , et al. Activation of the TGFbeta pathway impairs endothelial to haematopoietic transition. Sci Rep. Takubo K , Goda N , Yamada W , et al. Regulation of the HIF-1α level is essential for hematopoietic stem cells. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Navbar Search Filter Journal of Leukocyte Biology This issue Biological Sciences Immunology Molecular and Cell Biology Books Journals Oxford Academic Mobile Enter search term Search. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Materials and Methods. Journal Article. Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals. Yong Dong , Yong Dong. Oxford Academic. Ju Bai. Yimeng Zhang. Ya Zhou. Xu Pan. Xiaohong Li. Qiongxiu Zhou. Yijin Chen. Mowen Lai.
Introduction	Revista Brasileira de Farmacognosia Diabetes Reegneration Alpha-lipoic acid and cellular regeneration, — A Alpha-lipoic acid and cellular regeneration Alpha-lipolc dose of mg LA for 70 Alphs-lipoic reduced serum lipid Anxiety relief programs Androne et al. alpha-Lipoic acid: a metabolic antioxidant which regulates NF-kappa B signal transduction and protects against oxidative injury. The capacity of this substance to neutralize ROS, lessen oxidative stress, and trigger apoptosis is the fundamental mechanism underlying its effectiveness against various diseases and chronic disorders.
Top bar navigation	Several studies have provided facts that acts as a biological antioxidant and plays a leading function in cellular growth due to its ability to scavenge reactive oxygen species and renew endogenous antioxidants Attia et al. Vascular superoxide production by NAD P H oxidase: association with endothelial dysfunction and clinical risk factors. Alpha lipoic acid attenuates ER stress and improves glucose uptake through DNAJB3 cochaperone. The larger dose pill is to large to swallow. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. Article CAS PubMed PubMed Central Google Scholar Valdecantos, M.
Alpha Lipoic Acid	However, further work is necessary to assess the potential therapeutic roles for other diabetes-associated complications such as retinopathy and cataract. The lack of clear-cut benefits in some of the clinical trials to date does not disprove the benefits of ALA. It is believed that better designed experiments with appropriate doses, duration, and the selection of populations based on a specific pathophysiology may provide evidence for some of the hidden therapeutic potential of ALA. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Abbasi, F. Plasma concentrations of asymmetric dimethylarginine are increased in patients with type 2 diabetes mellitus. Pubmed Abstract Pubmed Full Text CrossRef Full Text. Achan, V. 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Combination of alpha lipoic acid thioctic acid , silymarin, and selenium: three case histories. Munich ; 94 Suppl. Berlett, B. Protein oxidation in aging, disease, and oxidative stress. Biewenga, G. The pharmacology of the antioxidant lipoic acid. Bilska, A. Lipoic acid the drug of the future? Böger, R. Asymmetric dimethylarginine ADMA : a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 98, — Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease. Circulation 95, — Bonomi, F. Molecular aspects of the removal of ferritin-bound iron by DL-dihydrolipoate. Acta , — Boullier, A. Scavenger receptors, oxidized LDL, and atherosclerosis. Brasier, A. The NF-kappaB regulatory network. Brownlee, M. Biochemistry and molecular cell biology of diabetic complications. Nature , — Advanced products of nonenzymatic glycosylation and the pathogenesis of diabetic vascular disease. Diabetes Metab. 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Impaired inhibitory G-protein function contributes to increased calcium currents in rats with diabetic neuropathy. Han, D. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 6, — Haritoqlou, C. Alpha lipoic acid for the prevention of diabetic macular edema. Ophthalmologica , — Harrison, E. The metabolism of dl- 1,C lipoic acid in the rat. Hawley, S. Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Heinisch, B. Alpha-lipoic acid improves vascular endothelial function in patients with type 2 diabetes: a placebo-controlled randomized trial. Heitzer, T. Beneficial effects of alpha-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress. Hermann, R. 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Diabetologia 45, — Treatment with alpha-lipoic acid reduces asymmetric dimethylarginine in patients with type 2 diabetes mellitus. Moini, H. Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid. Montagnani, M. Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells. Morcos, M. Effect of alpha-lipoic acid on the progression of endothelial cell damage and albuminuria in patients with diabetes mellitus: an exploratory study. Mottley, C. Sulfur-centered radical formation from the antioxidant dihydrolipoic acid. Musi, N. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 51, — Nagamatsu, M. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care 18, — Nickander, K. 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Schalkwijk, C. Pathophysiological role of amadori-glycated proteins in diabetic microangiopathy. Schepkin, V. NMR study of lipoic acid binding to bovine serum albumin. Unable to add item to List. Please try again. Sorry, there was a problem. There was an error retrieving your Wish Lists. List unavailable. Other Sellers on Amazon. Not added. Sold by: GNC. Image Unavailable Image not available for Color:. VIDEOS ° VIEW IMAGES. GNC Alpha-Lipoic Acid mg Supports Antioxidant Regeneration and Plays an Important Role in Cell Energy Metabolism 60 Caplets. Visit the GNC Store. Search this page. Amazon's Choice highlights highly rated, well-priced products available to ship immediately. Size: 60 Servings Pack of 1. Purchase options and add-ons. Brand GNC Unit Count About this item GNC Alpha-Lipoic Acid mg: Support Healthy Cells GNC Alpha-Lipoic Acid mg is an antioxidant that helps protect against cellular damage. This FUEL CELLULAR ENERGY: As you age, cell energy production declines. Report an issue with this product or seller. Frequently bought together. This item: GNC Alpha-Lipoic Acid mg Supports Antioxidant Regeneration and Plays an Important Role in Cell Energy Metabolism 60 Caplets. Get it Feb 14 - GNC CoQ mg - 60 Softgels. Get it as soon as Wednesday, Feb Total price:. To see our price, add these items to your cart. Try again! Added to Cart. Add both to Cart. These items are shipped from and sold by different sellers. Show details Hide details. Choose items to buy together. Similar items that may ship from close to you. Page 1 of 1 Start over Page 1 of 1. Previous page. Best Naturals Alpha Lipoic Acid mg Capsules. Amazon's Choice. Natrol Alpha Lipoic Acid Capsules, Antioxidant Protection, ALA, Helps Protect Against Cellular Oxidation and Age-Related Damage, Whole Body Cell Rejuvenation, mg, 50 Count. Thorne Alpha-Lipoic Acid - mg - Supplement Liver Detox, Antioxidant Support, Nerve Health and Mental Sharpness - 60 Capsules. Best Naturals Alpha Lipoic Acid mg Capsules Count Pack of 2. Next page. Compare with similar items This Item. Nutricost Alpha Lipoic Acid mg Per Serving Capsules, 60 Servings - Plant Based Caps, Non-GMO. ZEAL NATURALS. Antioxidant, Immune Support. Metabolism Management, Brain Health Support, Heart Health Support. Brief content visible, double tap to read full content. Full content visible, double tap to read brief content. Help others learn more about this product by uploading a video! Important information Legal Disclaimer Statements regarding dietary supplements have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease or health condition. Looking for specific info? Customer reviews. How customer reviews and ratings work Customer Reviews, including Product Star Ratings help customers to learn more about the product and decide whether it is the right product for them. Learn more how customers reviews work on Amazon. Images in this review. Reviews with images. See all photos. All photos. Frasco rajado. Al abrir el producto vi q estaba rajada la tapa ,quisiera devolver el producto pero la verdad me queda lejos la tienda gastó más en gasolina , así q ni modo. More Hide. Thank you for your feedback. Sorry, there was an error. Sorry we couldn't load the review. Sort reviews by Top reviews Most recent Top reviews. Top reviews from the United States. Translate all reviews to English. There was a problem filtering reviews right now. Please try again later. Size: 60 Count Pack of 1 Verified Purchase. Muy rápido. Translate review to English. Take it for breakfast and dinner. MD recommended. Para bajar los trigliceridos, es un excelente antiinflamatorio.
Alpha Lipoic Acid - ALA | Regeneration Health	α-Lipoic acid drives pyruvate dehydrogenase by downregulating aerobic glycolysis and activation of apoptosis in breast cancer cells, lactate production, induces apoptosis, and diminishes cell viability, implying that the inadequate uptake might be due to reduced cell death caused by α-lipoic acid Feuerecker et al. Customer Service. Tatar A, Korkmaz M, Yayla M, et al. It can be formulated in the form of nanostructure lipid carriers, solid lipid nanoparticles, and nano-emulsion. A Knocking down the expression of DNAJB3 and HSP72 mRNA with 20 nM of specific siRNA reduced significantly the endogenous expression of DNAJB3 and HSP72 mRNA. After 8 h of incubation, cells were stimulated with 0.

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