The Experts below are selected from a list of 279 Experts worldwide ranked by ideXlab platform
Lester Packer - One of the best experts on this subject based on the ideXlab platform.
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Lipoic Acid energy metabolism and redox regulation of transcription and cell signaling
Journal of Clinical Biochemistry and Nutrition, 2010Co-Authors: Lester Packer, Enrique CadenasAbstract:The role of R-α-Lipoic Acid as a cofactor (lipoyllysine) in mitochondrial energy metabolism is well established. Lipoic Acid non-covalently bound and exogenously administered to cells or supplemented in the diet is a potent modulator of the cell’s redox status. The diversity of beneficial effects of Lipoic Acid in a variety of tissues can be mechanistically viewed in terms of thiol/disulfide exchange reactions that modulate the environment’s redox and energy status. Lipoic Acid-driven thiol/disulfide exchange reactions appear critical for the modulation of proteins involved in cell signaling and transcription factors. This review emphasizes the effects of Lipoic Acid on PI3K and AMPK signaling and related transcriptional pathways that are integrated by PGC-1α, a critical regulator of energy homoestasis. The effects of Lipoic Acid on the neuronal energy-redox axis are largely reviewed in terms of their outcomes for aging and age-related neurodegenerative diseases.
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Lipoic Acid: Energy Production, Antioxidant Activity and Health Effects - Lipoic Acid : energy production, antioxidant activity and health effects
2008Co-Authors: Mulchand S. Patel, Lester PackerAbstract:Discovery molecular structure A Trail of Research on Lipoic Acid, L.J. Reed Lipoic Acid Biosynthesis, N.M. Nesbitt, R.M. Cicchillo, K.H. Lee, T.L. Grove, and S.J. Booker The Search for Potent alpha-Lipoic Acid Derivatives: Chemical and Pharmacological Aspects, M. Ben Yakir, Y. Katzhendler, and S. Sasson Novel Indole Lipoic Acid Derivatives: Synthesis and their Antioxidant Effects, A.S. Gurkan and E. Buyukbingol Metabolic aspects The alpha-keto Acid Dehydrogenase Complexes and Glycine Cleavage System: Their Involvement in Pathways of Carbohydrate, Protein, and Fat Metabolism, R.A. Harris, N.H. Jeoung, M. Joshi, and B. Hwang Pyruvate Dehydrogenase Complex Regulation and Lipoic Acid, L. Korotchkina and M.S. Patel Role of Lipoyl Domains in the Function and Regulation of the Mammalian Pyruvate Dehydrogenase Complex, T.E. Roche, T. Peng, L. Hu, Y. Hiromasa, H. Bao, and X. Gong Inactivation and Inhibition of alpha-ketoglutarate Dehydrogenase: Oxidative Modulation of Lipoic Acid, K.M. Humphries, A.C. Nulton-Persson, and L.I. Szweda Lipoate-Protein Ligase A: Structure and Function, K. Fujiwara, H. Hosaka, A. Nakagawa, and Y. Motokawa A Review of the Stability & Preliminary Evaluation of the Plasma Pharmacokinetics of R-Lipoic Acid & R-DihydroLipoic Acid Dosage Forms in Human Plasma from Healthy Volunteers, D.A. Carlson, K.L. Young, S.J. Fischer, D.M. Dye, M. Chau, and H. Ulrich The Pharmacokinetics, Metabolism and Renal Excretion of alpha-Lipoic Acid and its Main Metabolites in Humans, J. Teichert and R. Preiss Modulation of Cellular Redox and Metabolic Status by Lipoic Acid, D. Han and L. Packer The "Redoxin" Connection of Lipoic Acid, J.A. Barcena, P. Porras, C.A. Padilla, J. Peinado, J.R. Pedrajas, E. Martinez-Galisteo, and R. Requejo Lipoic Acid as an Inducer of Phase II Detoxification Enzymes through Activation of Nrf2-dependent Gene Expression, K. Peterson Shay, S. Shenvi and T.M. Hagen Clinical aspects Deficiency Disorders of Components of the PDH Complex: E2, BP & E3 Deficiencies, J.M. Cameron, M.C. Maj, and B.H. Robinson The Relationship between Primary Biliary Cirrhosis and Lipoic Acid, C. Selmi, X.S. He, C.L. Bowlus, and M.E. Gershwin Effects of Lipoic Acid on Insulin Action in Animal Models of Insulin Resistance, E.J. Henriksen and S. Jacob Activation of Cytoprotective Signaling Pathways by Alpha-Lipoic Acid, A.K. Kiemer and B. Diesel Selenotrisulfide Derivatives of Alpha Lipoic Acid: Potential Use as a Novel Topical Antioxidant, W.T. Self Alpha-Lipoic Acid: A Potent Mitochondrial Nutrient for Improving Memory Deficit, Oxidative Stress, and Mitochondrial Dysfunction, J. Liu Effects of Alpha-Lipoic Acid on AMP-Activated Kinase in Different Tissues: Therapeutic Implications for the Metabolic Syndrome, E.H. Koh, E. H. Cho, M.-S. Kim, J.-Y. Park, and K.-U. Lee
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α-Lipoic Acid
Nutrition and Immunology, 2000Co-Authors: John K. Lodge, Lester PackerAbstract:There is increasing evidence that thiols play a role in various biological processes. This arises from their ability to undergo redox reactions; thus, they can act as efficient electron donators or acceptors. α-Lipoic Acid is a dithiol-containing compound that plays an essential role in mitochondrial dehydrogenase reactions, but it has recently gained considerable interest as an antioxidant. Further investigations have shown lipoate to be an effective redox modulator of cell signaling and gene transcription. The various effects of α-Lipoic Acid at a cellular level are discussed here, highlighting the remarkable therapeutic potential for lipoate in a variety of disorders where oxidative stress is a factor.
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Natural Sources of Lipoic Acid in Plant and Animal Tissues
Antioxidant Food Supplements in Human Health, 1999Co-Authors: John K. Lodge, Lester PackerAbstract:Publisher Summary Naturally occurring Lipoic Acid is known to play a fundamental role in metabolism, serving as a cofactor in enzyme complexes, which function at strategic points in carbohydrate metabolism, citric-Acid cycle, and amino-Acid catabolism. In the last decade, experimental evidence has increased suggesting free Lipoic Acid to be a powerful antioxidant and redox regulator, and, as such, a potentially useful therapeutic tool. It is important that the distribution and content of Lipoic Acid in plants and animals be ascertained. Therefore, a method for measuring the naturally occurring protein-bound form of Lipoic Acid (lipoyllysine) has been developed, and this method has been used to measure the lipoyllysine content of various plant and animal tissues. In lipoate-containing enzymes (α-keto Acid dehydrogenases), Lipoic Acid is bound covalently to a lysine residue. This is an important consideration for determination as the release of Lipoic Acid is crucial. Previous methods have tried to overcome this problem via hydrolysis with strong Acid/base; however, a larger amount of Lipoic Acid is lost by such methods, and recoveries of only 50% have been reported, and no more than 70% have been found. To overcome this problem, proteolytic hydrolysis was introduced to liberate Lipoic Acid. This also has the advantage of liberating the actual protein-bound form (lipoyllysine). Lipoic Acid from animal tissues has been determined previously, but with methods of detection such as refractive index, ultraviolet, and GC mass spectroscopy. The former methods are inadequate as tissue hydrolysates contain a large amount of contaminants, which absorb around 330 nm, and GC methods require prior derivatization. To overcome these problems, an electrochemical detection system was introduced.
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Alpha-Lipoic Acid in liver metabolism and disease.
Free radical biology & medicine, 1998Co-Authors: Juanita Bustamante, Lester Packer, Hans J. Tritschler, John K. Lodge, Lucia Marcocci, Bertrand H. RihnAbstract:R-alpha-Lipoic Acid is found naturally occurring as a prosthetic group in alpha-keto Acid dehydrogenase complexes of the mitochondria, and as such plays a fundamental role in metabolism. Although this has been known for decades, only recently has free supplemented alpha-Lipoic Acid been found to affect cellular metabolic processes in vitro, as it has the ability to alter the redox status of cells and interact with thiols and other antioxidants. Therefore, it appears that this compound has important therapeutic potential in conditions where oxidative stress is involved. Early case studies with alpha-Lipoic Acid were performed with little knowledge of the action of alpha-Lipoic Acid at a cellular level, but with the rationale that because the naturally occurring protein bound form of alpha-Lipoic Acid has a pivotal role in metabolism, that supplementation may have some beneficial effect. Such studies sought to evaluate the effect of supplemented alpha-Lipoic Acid, using low doses, on lipid or carbohydrate metabolism, but little or no effect was observed. A common response in these trials was an increase in glucose uptake, but increased plasma levels of pyruvate and lactate were also observed, suggesting that an inhibitory effect on the pyruvate dehydrogenase complex was occurring. During the same period, alpha-Lipoic Acid was also used as a therapeutic agent in a number of conditions relating to liver disease, including alcohol-induced damage, mushroom poisoning, metal intoxification, and CCl4 poisoning. Alpha-Lipoic Acid supplementation was successful in the treatment for these conditions in many cases. Experimental studies and clinical trials in the last 5 years using high doses of alpha-Lipoic Acid (600 mg in humans) have provided new and consistent evidence for the therapeutic role of antioxidant alpha-Lipoic Acid in the treatment of insulin resistance and diabetic polyneuropathy. This new insight should encourage clinicians to use alpha-Lipoic Acid in diseases affecting liver in which oxidative stress is involved.
Aalt Bast - One of the best experts on this subject based on the ideXlab platform.
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The pharmacology of the antioxidant: Lipoic Acid
General Pharmacology, 1997Co-Authors: Gerreke Ph. Biewenga, Guido R.m.m. Haenen, Aalt BastAbstract:1. Lipoic Acid is an example of an existing drug whose therapeutic effect has been related to its antioxidant activity. 2. Antioxidant activity is a relative concept: it depends on the kind of oxidative stress and the kind of oxidizable substrate (e.g., DNA, lipid, protein). 3. In vitro, the final antioxidant activity of Lipoic Acid is determined by its concentration and by its antioxidant properties. Four antioxidant properties of Lipoic Acid have been studied: its metal chelating capacity, its ability to scavenge reactive oxygen species (ROS), its ability to regenerate endogenous antioxidants and its ability to repair oxidative damage. 4. DihydroLipoic Acid (DHLA), formed by reduction of Lipoic Acid, has more antioxidant properties than does Lipoic Acid. Both DHLA and Lipoic Acid have metal chelating capacity and scavenge ROS, whereas only DHLA is able to regenerate endogenous antioxidants and to repair oxidative damage. 5. As a metal chelator, Lipoic Acid was shown to provide antioxidant activity by chelating Fe2+ and CU2+; DHLA can do so by chelating Cd2+. 6. As scavengers of ROS, Lipoic Acid and DHLA display antioxidant activity in most experiments, whereas, in particular cases, pro oxidant activity has been observed. However, Lipoic Acid can act as an antioxidant against the pro oxidant activity produced by DHLA. 7. DHLA has the capacity to regenerate the endogenous antioxidants vitamin E, vitamin C and glutathione. 8. DHLA can provide peptide methionine sulfoxide reductase with reducing equivalents. This enhances the repair of oxidatively damaged proteins such as α-1 antiprotease. 9. Through the lipoamide dehydrogenase-dependent reduction of Lipoic Acid, the cell can draw on its NADH pool for antioxidant activity additionally to its NADPH pool, which is usually consumed during oxidative stress. 10. Within drug-related antioxidant pharmacology, Lipoic Acid is a model compound that enhances understanding of the mode of action of antioxidants in drug therapy.
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Reduction of Lipoic Acid by lipoamide dehydrogenase
Biochemical pharmacology, 1996Co-Authors: Gerreke Ph. Biewenga, Guido R.m.m. Haenen, Marco A. Dorstijn, Justus V. Verhagen, Aalt BastAbstract:Racemic Lipoic Acid is therapeutically applied in pathologies in which free radicals are involved. The in vivo reduction of Lipoic Acid may play an essential role in its antioxidant effect. It was found that mitochondrial lipoamide dehydrogenase (LipDH, EC 1.8.1.4.) reduces the R-enantiomer 28 times faster than the S-enantiomer of Lipoic Acid. Moreover, it was observed that the metabolites of Lipoic Acid, bisnor-, tetranor-, and beta-Lipoic Acid are poor substrates of LipDH. S-Lipoic Acid inhibits the reduction of the R enantiomer only at relatively high concentrations. The reduction of R-Lipoic Acid by mitochondria-rich tissues may proceed smoothly, even if the racemic mixture is applied. This is of importance in elucidating the molecular mechanism of the pharmacotherapeutic effect of Lipoic Acid.
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Reaction of Lipoic Acid with ebselen and hypochlorous Acid.
Methods in enzymology, 1995Co-Authors: Gerreke Ph. Biewenga, Aalt BastAbstract:Publisher Summary This chapter discusses the reaction of Lipoic Acid with ebselen and hypochlorous Acid. Lipoic Acid plays a pivotal role in energy metabolism. Its antioxidant activity, however, is also recognized in normal and pathological conditions. In vivo , Lipoic Acid shuffles between its reduced [dihydroLipoic Acid or 6,8-dimercaptooctanoic Acid, L(SH) 2 ] and oxidized state (Lipoic Acid or 1,2-dithiolane-3-pentanoic Acid). DihydroLipoic Acid is characterized by two thiol groups per molecule; these thiol groups provide the compound with its good antioxidant efficacy. In this regard, its role in the glutathione (GSH) peroxidase-like activity of the small molecule ebselen is interesting. Ebselen is an organoselenium compound with antiinflammatory activity. It catalyzes the reduction of peroxides by GSH. Replacing GSH by L(SH) 2 improves the peroxidase-like activity of ebselen. In the oxidized state of Lipoic Acid, the two sulfur atoms are attached to each other as part of a five-membered 1,2-dithiolane ring. The strain in this ring is responsible for a unique reactivity. An example of this reactivity is the ability of this molecule to scavenge hypochlorous Acid (HOCl). By scavenging the neutrophil oxidant HOCl, the elastase inhibitor α l -antiproteinase (API) is protected from oxidation. The reaction scheme for the catalysis of the GSH peroxidase reaction by ebselen is analogous to that of the enzyme.
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Lipoic Acid Favors Thiolsulfinate Formation After Hypochlorous Acid Scavenging: A Study with Lipoic Acid Derivatives
Archives of biochemistry and biophysics, 1994Co-Authors: G.p. Biewenga, J. Dejong, Aalt BastAbstract:Abstract Lipoic Acid, the oxidized form of 6,8-dimercapto-octanoic Acid has a strained cyclic disulfide in a 1,2-dithiolane ring. Recently its antioxidant activity gained attention. Hypochlorous Acid (HOCl) is an oxidant produced by neutrophils. A prominent effect of HOCl is the inactivation of α-1-antiproteinase. Due to this inactivation, the ability of α-1-antiproteinase to inhibit elastase is lost. The resulting higher activity of elastase is held responsible for tissue damage in lung emphysema. We studied the HOCl scavenging capability of three metabolites of Lipoic Acid: tetranor-, bisnor-, and β-Lipoic Acid. To obtain some insight on the molecular basis of HOCl scavenging 1,2-dithiane-4,5-diol, cystine, Lipoic Acid methyl ester, and lipoamide were also included in the study. The extent of α-1-antiproteinase inactivation by HOCl in the presence of scavenger was taken as a parameter to quantify the scavenging activity. It was found that Lipoic Acid, tetranor- and bisnorLipoic Acid, Lipoic Acid methyl ester, and lipoamide all showed the same activity toward HOCl. β-Lipoic Acid, 1,2-dithiane-4,5-diol and cystine were less active. The products of Lipoic Acid after reaction with HOCl were studied using GC/MS. Indications for thiolsulfinate formation were found by comparing these products with the GC/MS profile of β-Lipoic Acid. Thiolsulfinate formation may also be suggested in the reaction of tetranor- and bisnorLipoic Acid and Lipoic Acid methyl ester with HOCl. The present results show an antioxidant activity of the metabolites tetranor- and bisnorLipoic Acid. The 1,2-dithiolane ring may enhance the reactivity toward HOCl compared to less strained disulfides, resulting in the formation a thiolsulfinate.
Yoko Yamaguchi - One of the best experts on this subject based on the ideXlab platform.
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Novel nanocapsule of α‐Lipoic Acid reveals pigmentation improvement: α‐Lipoic Acid stimulates the proliferation and differentiation of keratinocyte in murine skin by topical application
Experimental Dermatology, 2019Co-Authors: Yoshiki Kubota, Mina Musashi, Teruaki Nagasawa, Nanako Shimura, Rie Igarashi, Yoko YamaguchiAbstract:α-Lipoic Acid is amphipathic with low molecular sulphur-containing fatty Acid and has strong antioxidant effects. It has been used at the purposes of anti-ageing, treatment of diabetic neuropathy, and supplement as antioxidant. Though α-Lipoic Acid is normally administered in oral or injection, it has not been used in a topical use via skin because of its bad penetration. We developed the novel nanocapsule of α-Lipoic Acid, named α-lipoactive (nLA), to improve skin permeability. The nLA is constructed as micelles of α-Lipoic Acid mixed with the non-ionic surfactant, and its surface of the micelles was coated with inorganic metal salts. It is water soluble and has a diameter of approximately 8-15 nm. After nLA was applied to the murine skin, epidermal thickening was observed. It was confirmed that this effect is caused by α-Lipoic Acid molecule, but not by the raw material used for encapsulation. In in vivo experiments, it was found that nLA is very effective for improving UV-induced pigmentation and epidermal thickening. Our findings suggest that nanoencapsulation of α-Lipoic Acid is considerably effective for topical application.
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Novel nanocapsule of α-Lipoic Acid reveals pigmentation improvement: α-Lipoic Acid stimulates the proliferation and differentiation of keratinocyte in murine skin by topical application.
Experimental dermatology, 2019Co-Authors: Yoshiki Kubota, Mina Musashi, Teruaki Nagasawa, Nanako Shimura, Rie Igarashi, Yoko YamaguchiAbstract:α-Lipoic Acid is amphipathic with low molecular sulphur-containing fatty Acid and has strong antioxidant effects. It has been used at the purposes of anti-ageing, treatment of diabetic neuropathy, and supplement as antioxidant. Though α-Lipoic Acid is normally administered in oral or injection, it has not been used in a topical use via skin because of its bad penetration. We developed the novel nanocapsule of α-Lipoic Acid, named α-lipoactive (nLA), to improve skin permeability. The nLA is constructed as micelles of α-Lipoic Acid mixed with the non-ionic surfactant, and its surface of the micelles was coated with inorganic metal salts. It is water soluble and has a diameter of approximately 8-15 nm. After nLA was applied to the murine skin, epidermal thickening was observed. It was confirmed that this effect is caused by α-Lipoic Acid molecule, but not by the raw material used for encapsulation. In in vivo experiments, it was found that nLA is very effective for improving UV-induced pigmentation and epidermal thickening. Our findings suggest that nanoencapsulation of α-Lipoic Acid is considerably effective for topical application.
Hans J. Tritschler - One of the best experts on this subject based on the ideXlab platform.
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Alpha-Lipoic Acid in liver metabolism and disease.
Free radical biology & medicine, 1998Co-Authors: Juanita Bustamante, Lester Packer, Hans J. Tritschler, John K. Lodge, Lucia Marcocci, Bertrand H. RihnAbstract:R-alpha-Lipoic Acid is found naturally occurring as a prosthetic group in alpha-keto Acid dehydrogenase complexes of the mitochondria, and as such plays a fundamental role in metabolism. Although this has been known for decades, only recently has free supplemented alpha-Lipoic Acid been found to affect cellular metabolic processes in vitro, as it has the ability to alter the redox status of cells and interact with thiols and other antioxidants. Therefore, it appears that this compound has important therapeutic potential in conditions where oxidative stress is involved. Early case studies with alpha-Lipoic Acid were performed with little knowledge of the action of alpha-Lipoic Acid at a cellular level, but with the rationale that because the naturally occurring protein bound form of alpha-Lipoic Acid has a pivotal role in metabolism, that supplementation may have some beneficial effect. Such studies sought to evaluate the effect of supplemented alpha-Lipoic Acid, using low doses, on lipid or carbohydrate metabolism, but little or no effect was observed. A common response in these trials was an increase in glucose uptake, but increased plasma levels of pyruvate and lactate were also observed, suggesting that an inhibitory effect on the pyruvate dehydrogenase complex was occurring. During the same period, alpha-Lipoic Acid was also used as a therapeutic agent in a number of conditions relating to liver disease, including alcohol-induced damage, mushroom poisoning, metal intoxification, and CCl4 poisoning. Alpha-Lipoic Acid supplementation was successful in the treatment for these conditions in many cases. Experimental studies and clinical trials in the last 5 years using high doses of alpha-Lipoic Acid (600 mg in humans) have provided new and consistent evidence for the therapeutic role of antioxidant alpha-Lipoic Acid in the treatment of insulin resistance and diabetic polyneuropathy. This new insight should encourage clinicians to use alpha-Lipoic Acid in diseases affecting liver in which oxidative stress is involved.
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DECOMPOSITION OF ALPHA -Lipoic Acid DERIVATIVES BY PHOTOIRRADIATION-FORMATION OF DIHYDROLipoic Acid FROM ALPHA -Lipoic Acid
Biochemistry and molecular biology international, 1996Co-Authors: S. Matsugo, Derick Han, Hans J. Tritschler, Lester PackerAbstract:Due to its strained five-membered ring, alpha-Lipoic Acid (LA) has an absorption band around 330 nm, which is used to quantify its concentration. In order to obtain information for the homolytic rupture of the S-S bond and the formation of dihydroLipoic Acid (DHLA), the photochemical reaction of Lipoic Acid was examined in the presence or absence of ascorbic Acid upon exposure to UVA light. The absorption band of alpha-Lipoic Acid at around 330 nm disappeared by photoirradiation, which corresponds to the rupture of S-S bond of the 1,2-dithiolane ring in Lipoic Acid. HPLC-Electrochemical Detection (ECD) analysis of Lipoic Acid showed significant formation of dihydroLipoic Acid and other thiols. The formation of thiols from the photoreaction of Lipoic Acid was also confirmed by the Ellman method. The formation of thiols from Lipoic Acid was completely time-dependent and the formation of the thiols increased upto 55%. Similar results were obtained in the photochemical reactions of short-chain analogues, bisnor- and tetranor-Lipoic Acid. On the other hand, beta-Lipoic Acid was quite stable, no photodecomposition of beta-Lipoic Acid was observed in the UV region. The formation of thiols including dihydroLipoic Acid from Lipoic Acid can be explained by considering the rupture of S-S bond, which results in the formation of the dithiyl radicals of alpha-Lipoic Acid. It is proposed that intra- and intermolecular hydrogen abstraction of the dithyl radical produces thiols including dihydroLipoic Acid as final products.
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alpha Lipoic Acid as a biological antioxidant
Free Radical Biology and Medicine, 1995Co-Authors: Lester Packer, Eric Witt, Hans J. TritschlerAbstract:alpha-Lipoic Acid, which plays an essential role in mitochondrial dehydrogenase reactions, has recently gained considerable attention as an antioxidant. Lipoate, or its reduced form, dihydrolipoate, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, hypochlorous Acid, peroxyl radicals, and singlet oxygen. It also protects membranes by interacting with vitamin C and glutathione, which may in turn recycle vitamin E. In addition to its antioxidant activities, dihydrolipoate may exert prooxidant actions through reduction of iron. alpha-Lipoic Acid administration has been shown to be beneficial in a number of oxidative stress models such as ischemia-reperfusion injury, diabetes (both alpha-Lipoic Acid and dihydroLipoic Acid exhibit hydrophobic binding to proteins such as albumin, which can prevent glycation reactions), cataract formation, HIV activation, neurodegeneration, and radiation injury. Furthermore, lipoate can function as a redox regulator of proteins such as myoglobin, prolactin, thioredoxin and NF-kappa B transcription factor. We review the properties of lipoate in terms of (1) reactions with reactive oxygen species; (2) interactions with other antioxidants; (3) beneficial effects in oxidative stress models or clinical conditions.
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Glutathione reductase and lipoamide dehydrogenase have opposite stereospecificities for α-Lipoic Acid enantiomers
Biochemical and biophysical research communications, 1995Co-Authors: Uri Pick, Hans J. Tritschler, N. Haramaki, A. Constantinescu, G.j. Handelman, Lester PackerAbstract:Abstract The reduction of exogenous α-Lipoic Acid to dihydrolipoate by mammalian cells and tissues confers additional antioxidant protection to the cell. Both (R+) and (S−) isomers of α-Lipoic Acid were analyzed as substrates with glutathione reductase from several sources and with mammalian lipoamide dehydrogenase. Mammalian glutathione reductase catalyzed faster reduction of (S)-Lipoic Acid (1.4-2.4-fold greater activity) than of (R)-Lipoic Acid, whereas lipoamide dehydrogenase had a very marked preference for (R)-Lipoic Acid (18-fold greater activity) over (S)-Lipoic Acid. Mammalian glutathione reductase showed better affinity for (S)-Lipoic Acid substrate; Km values were 3.5 mM for (S)-Lipoic Acid and and 7 mM for (R)-Lipoic Acid. Glutathione reductase from yeast reduced Lipoic Acid less efficiently than the mammalian enymes, had a Km for both stereoisomers of about 10 mM, and showed little stereospecificity. Although (S)-Lipoic Acid is not formed in nature, these findings indicate that exogenous (S)-Lipoic Acid may have a useful role as an antioxidant for mammalian systems.
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alpha Lipoic Acid supplementation prevents symptoms of vitamin e deficiency
Biochemical and Biophysical Research Communications, 1994Co-Authors: Maurizio Podda, Hans J. Tritschler, H Ulrich, Lester PackerAbstract:alpha-Lipoic Acid, an essential cofactor in mitochondrial dehydrogenases, has recently been shown to be a potent antioxidant in vitro, as well as being capable of regenerating vitamin E in vitro. In this study, using a new animal model for rapid vitamin E deficiency in adult animals and a new technique for tissue extraction of oxidized and reduced alpha-Lipoic Acid, we examined the antioxidant action of alpha-Lipoic Acid in vivo. Vitamin E-deficient adult hairless mice displayed obvious symptoms of deficiency within five weeks, but if the diet was supplemented with alpha-Lipoic Acid the animals were completely protected. At five weeks on a vitamin E-deficient diet animals exhibited similar decreases in tissue vitamin E levels, whether supplemented or unsupplemented with alpha-Lipoic Acid: vitamin E levels in liver, kidney, heart, and skin decreased 70 to 85%; levels in brain decreased only 25%. These data show that there was no effect of alpha-Lipoic Acid supplementation on vitamin E tissue concentrations, arguing against a role for alpha-Lipoic Acid in regenerating vitamin E in vivo.
Yoshiki Kubota - One of the best experts on this subject based on the ideXlab platform.
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Novel nanocapsule of α‐Lipoic Acid reveals pigmentation improvement: α‐Lipoic Acid stimulates the proliferation and differentiation of keratinocyte in murine skin by topical application
Experimental Dermatology, 2019Co-Authors: Yoshiki Kubota, Mina Musashi, Teruaki Nagasawa, Nanako Shimura, Rie Igarashi, Yoko YamaguchiAbstract:α-Lipoic Acid is amphipathic with low molecular sulphur-containing fatty Acid and has strong antioxidant effects. It has been used at the purposes of anti-ageing, treatment of diabetic neuropathy, and supplement as antioxidant. Though α-Lipoic Acid is normally administered in oral or injection, it has not been used in a topical use via skin because of its bad penetration. We developed the novel nanocapsule of α-Lipoic Acid, named α-lipoactive (nLA), to improve skin permeability. The nLA is constructed as micelles of α-Lipoic Acid mixed with the non-ionic surfactant, and its surface of the micelles was coated with inorganic metal salts. It is water soluble and has a diameter of approximately 8-15 nm. After nLA was applied to the murine skin, epidermal thickening was observed. It was confirmed that this effect is caused by α-Lipoic Acid molecule, but not by the raw material used for encapsulation. In in vivo experiments, it was found that nLA is very effective for improving UV-induced pigmentation and epidermal thickening. Our findings suggest that nanoencapsulation of α-Lipoic Acid is considerably effective for topical application.
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Novel nanocapsule of α-Lipoic Acid reveals pigmentation improvement: α-Lipoic Acid stimulates the proliferation and differentiation of keratinocyte in murine skin by topical application.
Experimental dermatology, 2019Co-Authors: Yoshiki Kubota, Mina Musashi, Teruaki Nagasawa, Nanako Shimura, Rie Igarashi, Yoko YamaguchiAbstract:α-Lipoic Acid is amphipathic with low molecular sulphur-containing fatty Acid and has strong antioxidant effects. It has been used at the purposes of anti-ageing, treatment of diabetic neuropathy, and supplement as antioxidant. Though α-Lipoic Acid is normally administered in oral or injection, it has not been used in a topical use via skin because of its bad penetration. We developed the novel nanocapsule of α-Lipoic Acid, named α-lipoactive (nLA), to improve skin permeability. The nLA is constructed as micelles of α-Lipoic Acid mixed with the non-ionic surfactant, and its surface of the micelles was coated with inorganic metal salts. It is water soluble and has a diameter of approximately 8-15 nm. After nLA was applied to the murine skin, epidermal thickening was observed. It was confirmed that this effect is caused by α-Lipoic Acid molecule, but not by the raw material used for encapsulation. In in vivo experiments, it was found that nLA is very effective for improving UV-induced pigmentation and epidermal thickening. Our findings suggest that nanoencapsulation of α-Lipoic Acid is considerably effective for topical application.