Abstract
Lipoic acid (LA) is globally known and its supplements are widely used. Despite its importance for the organism it is not considered a vitamin any more. The multiple metabolic forms and the differences in kinetics (absorption, distribution and excretion), as well as the actions of its enantiomers are analysed in the present article together with its biosynthetic path. The proteins involved in the transfer, biotransformation and activity of LA are mentioned. Furthermore, the safety and the toxicological profile of the compound are commented, together with its stability issues. Mechanisms of lipoic acid intervention in the human body are analysed considering the antioxidant and non-antioxidant characteristics of the compound. The chelating properties, the regenerative ability of other antioxidants, the co-enzyme activity and the signal transduction by the implication in various pathways will be discussed in order to be elucidated the pleiotropic effects of LA. Finally, lipoic acid integrating analogues are mentioned under the scope of the multiple pharmacological actions they acquire towards degenerative conditions.
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Akiba S, Matsugo S, Packer L, Konishi T (1998) Assay of protein-bound lipoic acid in tissues by a new enzymatic method. Anal Biochem 258:299–304
Gorąca A, Huk-Kolega H, Piechota A, Kleniewska P, Ciejka E, Skibska B (2011) Lipoic acid–biological activity and therapeutic potential. Pharmacol Rep 63:849–858
Morikawa T, Yasuno R, Wada H (2001) Do animal cells synthesize lipoic acid? Identification of a mouse cDNA encoding a lipoic acid synthase located in mitchondria. Fed Euro Biochem Soc 498:16–21
Brufani M, Figliola R (2014) (R)-α-lipoic acid oral liquid formulation: pharmacokinetic parameters and therapeutic efficacy. Acta Biomed 85:108–115
Takaishi N, Yoshida K, Satsu H, Shimizu M (2007) Transepithelial transport of alpha-lipoic acid across human intestinal Caco-2 cell monolayers. J Agric Food Chem 55:5253–5259
Zehnpfennig B, Wiriyasermkul P, Carlson DA, Quick M (2015) Interaction of α-lipoic acid with the human Na+/multivitamin transporter (hSMVT). J Biol Chem 290:16372–16382
Keith DJ, Butler JA, Bemer B, Dixon B, Johnson S, Garrard M, Hagen TM (2012) Age and gender dependent bioavailability of R- and R, S-α-lipoic acid: a pilot study. Pharmacol Res 66:199–206
Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM (2009) Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta 1790:1149–1160
Biewenga GP, Haenen GR, Bast A (1997) The pharmacology of the antioxidant lipoic acid. Gen Pharmacol 29:315–331
Schupke H, Hempel R, Peter G, Hermann R, Wessel K, Engel J, Kronbach T (2001) New metabolic pathways of alpha-lipoic acid. Drug Metab Dispos 29:855–862
May JM, Qu ZC, Nelson DJ (2006) Cellular disulfide-reducing capacity: an integrated measure of cell redox capacity. Biochem Biophys Res Commun 344:1352–1359
Teichert J, Preiss R (2002) High-performance liquid chromatographic assay for alpha-lipoic acid and five of its metabolites in human plasma and urine. J Chromatogr B Analyt Technol Biomed Life Sci 769:269–281
Yadav V, Marracci G, Lovera J, Woodward W, Bogardus K, Marquardt W, Shinto L, Morris C, Bourdette D (2005) Lipoic acid in multiple sclerosis: a pilot study. Mult Scler 11:159–165
Ziegler D, Hanefeld M, Ruhnau KJ, Meissner HP, Lobisch M, Schutte K, Gries FA (1995) Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN study). Diabetologia 38:1425–1433
Ziegler D, Hanefeld M, Ruhnau KJ, Hasche H, Lobisch M, Schutte K, Kerum G, Malessa R (1999) 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. Diabetes Care 22:1296–2130
Cakatay U, Kayali R, Kiziler AR, Aydemir B (2008) Postmitotic tissue selenium and manganese levels in alpha-lipoic acid-supplemented aged rats. Chem Biol Interact 171:306–311
Parente E, Colannino G, Picconi O, Monastra G (2017) Safety of oral alpha-lipoic acid treatment in pregnant women: a retrospective observational study. Eur Rev Med Pharmacol Sci 21:4219–4227
Kisanuki A, Kimpara Y, Oikado Y, Kado N, Matsumoto M, Endo K (2010) Ring-opening polymerization of lipoic acid and characterization of the polymer. J Polymer Sci Part A Polymer Chemistry 48:5247–5253
Carmine A, Domoto Y, Sakai N, Matile S (2013) Comparison of lipoic and asparagusic acid for surface-initiated disulfide-exchange polymerization. Chemistry 19:11558–11563
Bonifacic M, Asmus KD (1976) Free radical oxidation of organic disulfides. J Phys Chem 80:2426–2430
Chatgilialoglu C, Ferreri C (2010) Biomimetic chemistry: radical reactions in vesicle suspensions. In: Mukherjee A (ed) Biomimetics learning from nature. Chapter 6, InTech Publ
Yan LJ, Traber MG, Kobuchi H, Matsugo S, Tritschler HJ, Packer L (1996) Efficacy of hypochlorous acid scavengers in the prevention of protein carbonyl formation. Arch Biochem Biophys 327:330–334
Ou P, Tritschler HJ, Wolff SP (1995) Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant? Biochem Pharmacol 50:123–126
Bush AI (2002) Metal complexing agents as therapies for Alzheimer’s disease. Neurobiol Aging 23:1031–1038
Suh JH, Shigeno ET, Morrow JD, Cox B, Rocha AE, Frei B, Hagen TM (2001) Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)-(alpha)-lipoic acid. FASEB J 15:700–706
Han D, Handelman G, Marcocci L, Sen CK, Roy S, Kobuchi H, Tritschler HJ, Flohe L, Packer L (1997) Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. BioFactors 6:321–338
Suh JH, Wang H, Liu RM, Liu J, Hagen TM (2004) (R)-alpha-lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues: evidence for increased cysteine requirement for GSH synthesis. Arch Biochem Biophys 423:126–135
Hoshi T, Heinemann S (2001) Regulation of cell function by methionine oxidation and reduction. J Physiol 531(Pt 1):1–11
Sigalov AB, Stern LJ (2002) Dihydrolipoic acid as an effective cofactor for peptide methionine sulfoxide reductase in enzymatic repair of oxidative damage to both lipid-free and lipid-bound apolipoprotein a-I. Antioxid Redox Signal 4:553–557
Hiltunen JK, Autio KJ, Schonauer MS, Kursu VA, Dieckmann CL, Kastaniotis AJ (2010) Mitochondrial fatty acid synthesis and respiration. Biochim Biophys Acta 1797:1195–1202
Cronan JE (2016) Assembly of lipoic acid on its cognate enzymes: an extraordinary and essential biosynthetic pathway. Microbiol Mol Biol Rev 80:429–450
Frey PA, Booker SJ (2001) Radical mechanisms of S-adenosylmethionine-dependent enzymes. Adv Protein Chem 58:1–45
Cronan JE (2014) Biotin and lipoic acid: synthesis, attachment, and regulation. EcoSal Plus. https://doi.org/10.1128/ecosalplus.ESP-0001-2012
Solmonson A, DeBerardinis RJ (2018) Lipoic acid metabolism and mitochondrial redox regulation. J Biol Chem 293:7522–7530
Kumaran S, Patel MS, Jordan F (2013) Nuclear magnetic resonance approaches in the study of 2-oxo acid dehydrogenase multienzyme complexes–a literature review. Molecules 18:11873–11903
Pick U, Haramaki N, Constantinescu A, Handelman GJ, Tritschler HJ, Packer L (1995) Glutathione reductase and lipoamide dehydrogenase have opposite stereospecificities for alpha-lipoic acid enantiomers. Biochem Biophys Res Commun 206:724–730
Biewenga GP, Dorstijn MA, Verhagen JV, Haenen GR, Bast A (1996) Reduction of lipoic acid by lipoamide dehydrogenase. Biochem Pharmacol 51:233–238
Vomhof-Dekrey EE, Picklo MJ Sr (2012) The Nrf2-antioxidant response element pathway: a target for regulating energy metabolism. J Nutr Biochem 23:1201–1206
Copple IM, Goldring CE, Kitteringham NR, Park BK (2008) The Nrf2-Keap1 defence pathway: role in protection against drug-induced toxicity. Toxicol 246:24–33
Moini H, Tirosh O, Park YC, Cho KJ, Packer L (2002) R-alpha-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3 T3–L1 adipocytes. Arch Biochem Biophys 397:384–391
Rochette L, Ghibu S, Richard C, Zeller M, Cottin Y, Vergely C (2013) Direct and indirect antioxidant properties of α-lipoic acid and therapeutic potential. Mol Nutr Food Res 57:114–125
Konrad D, Somwar R, Sweeney G, Yaworsky K, Hayashi M, Ramlal T, Klip A (2001) The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. Diabetes 50:1464–1471
Ghibu S, Richard C, Vergely C, Zeller M, Cottin Y, Rochette L (2009) Antioxidant properties of an endogenous thiol: alpha-lipoic acid, useful in the prevention of cardiovascular diseases. J Cardiovasc Pharmacol 54:391–398
Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, Munzel U, Yakhno N, Raz I, Novosadova M, Maus J, Samigullin R (2006) Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care 29:2365–2370
Diesel B, Kulhanek-Heinze S, Holtje M, Brandt B, Holtje HD, Vollmar AM, Kiemer AK (2007) Alpha-lipoic acid as a directly binding activator of the insulin receptor: protection from hepatocyte apoptosis. Biochemistry 46:2146–2155
Jacob S, Streeper RS, Fogt DL, Hokama JY, Tritschler HJ, Dietze GJ, Henriksen EJ (1996) The antioxidant alpha-lipoic acid enhances insulin-stimulated glucose metabolism in insulin-resistant rat skeletal muscle. Diabetes 45:1024–1029
Heitzer T, Finckh B, Albers S, Krohn K, Kohlschutter A, Meinertz T (2001) 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. Free Radic Biol Med 31:53–61
Hagen TM, Moreau R, Suh JH, Visioli F (2002) Mitochondrial decay in the aging rat heart: evidence for improvement by dietary supplementation with acetyl-l-carnitine and/or lipoic acid. Ann NY Acad Sci 959:491–507
Skibska B, Goraca A (2015) The protective effect of lipoic acid on selected cardiovascular diseases caused by age-related oxidative stress. Oxid Med Cell Longev 2015:313021
Carrier B, Wen S, Zigouras S, Browne RW, Li Z, Patel MS, Williamson DL, Rideout TC (2014) Alpha-lipoic acid reduces LDL-particle number and PCSK9 concentrations in high-fat fed obese Zucker rats. PLoS ONE 9:e90863
Vasdev S, Gill V, Longerich L, Parai S, Gadag V (2003) Salt-induced hypertension in WKY rats: prevention by alpha-lipoic acid supplementation. Mol Cell Biochem 254:319–326
Maczurek A, Hager K, Kenklies M, Sharman M, Engel MR (2008) Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer’s disease. Adv Drug Deliv Rev 60:1463–1470
Sancheti H, Akopian G, Yin F, Brinton RD, Walsh JP, Cadenas E (2013) Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer’s disease. PLoS ONE 8:e69830
Guha M, Mackman N (2002) The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. J Biol Chem 277:32124–32132
Deng C, Sun Z, Tong G, Yi W, Ma L, Zhao B, Cheng L, Zhang J, Cao F, Yi D (2013) α-Lipoic acid reduces infarct size and preserves cardiac function in rat myocardial ischemia/reperfusion injury through activation of PI3K/Akt/Nrf2 pathway. PLoS ONE 8:e58371
Dudek M, Knutelska J, Bednarski M, Nowiński L, Zygmunt M, Bilska-Wilkosz A, Iciek M, Otto M, Żytka I, Sapa J, Włodek L, Filipek B (2014) Alpha lipoic acid protects the heart against myocardial post ischemia-reperfusion arrhythmias via KATP channel activation in isolated rat hearts. Pharmacol Rep 66:499–504
Packer L, Cadenas E (2011) Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling. J Clin Biochem Nutr 48:26–32
Kunt T, Forst T, Wilhelm A, Tritschler H, Pfuetzner A, Harzer O, Engelbach M, Zschaebitz A, Stofft E, Beyer J (1999) Alpha-lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products. Clin Sci 96:75–82
Kim HS, Kim HJ, Park KG, Kim YN, Kwon TK, Park JY, Lee KU, Kim JG, Lee IK (2007) Alpha-lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-kappaB transcriptional activity. Exp Mol Med 39:106–113
Chaudhary P, Marracci GH, Bourdette DN (2006) 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. J Neuroimmunol 175:87–96
Lee EY, Lee CK, Lee KU, Park JY, Cho KJ, Cho YS, Lee HR, Moon SH, Moon HB, Yoo B (2007) Alpha-lipoic acid suppresses the development of collagen-induced arthritis and protects against bone destruction in mice. Rheumatol Int 27:225–233
Schillace RV, Pisenti N, Pattamanuch N, Galligan S, Marracci GH, Bourdette DN, Carr DW (2007) Lipoic acid stimulates cAMP production in T lymphocytes and NK cells. Biochem Biophys Res Commun 354:259–264
Larghero P, Vene R, Minghelli S, Travaini G, Morini M, Ferrari N, Pfeffer U, Noonan DM, Albini A, Benelli R (2007) Biological assays and genomic analysis reveal lipoic acid modulation of endothelial cell behavior and gene expression. Carcinogenesis 28:1008–1020
Feuerecker B, Pirsig S, Seidl C, Aichler M, Feuchtinger A, Bruchelt G, Senekowitsch-Schmidtke R (2012) Lipoic acid inhibits cell proliferation of tumor cells in vitro and in vivo. Cancer Biol Ther 13:1425–1435
Tibullo D, Giallongo C, Puglisi F, Tomassoni D, Camiolo G, Cristaldi M, Brundo MV, Anfuso CD, Lupo G, Stampone T, Li Volti G, Amenta F, Avola R, Bramanti V (2017) Effect of lipoic acid on the biochemical mechanisms of resistance to Bortezomib in SH-SY5Y Neuroblastoma Cells. Mol Neurobiol 55:3344–3350
Zhang H, Jia H, Liu J, Ao N, Yan B, Shen W (2010) Combined R-α–lipoic acid and acetyl-L-carnitine exerts efficient preventative effects in a cellular model of Parkinson’s disease. J Cell Mol Med 14:215–225
Ferreira P, Militão G, Freitas R (2009) Lipoic acid effects on lipid peroxidation level, superoxide dismutase activity and monoamines concentration in rat hippocampus. Neurosci Lett 464:131–134
Molinari C, Morsanuto V, Ghirlanda S, Ruga S, Notte F, Gaetano L, Uberti F (2019) Role of combined lipoic acid and vitamin D3 on astrocytes as a way to prevent brain ageing by induced oxidative stress and iron accumulation. Oxid Med Cell Longev 2019:2843121
Morsanuto V, Galla R, Molinari C, Uberti F (2020) A new palmitoylethanolamide form combined with antioxidant molecules to improve its effectivess on neuronal aging. Brain Sci 10:457
Wollin SD, Jones PJ (2003) α-Lipoic acid and cardiovascular disease. J Nutr 133:3327–3330
Xing ZG, Yu GD, Qin L, Jiang F, Zhao WH (2015) Effects and mechanism of lipoic acid on beta-amyloid-intoxicated C6 glioma cells. Genet Mol Res 14:13880–13888
Hardas SS, Sultana R, Clark AM, Beckett TL, Szweda LI, Murphy P, Butterfielda DA (2013) Oxidative modification of lipoic acid by HNE in Alzheimer disease brain. Redox Biol 1:80–85
Dinicola S, Proietti S, Cucina A, Bizzarri M, Fuso A (2017) Alpha-lipoic acid downregulates IL-1β and IL-6 by DNA hypermethylation in SK-N-BE neuroblastoma cells. Antioxidants 6:74
Gomes MB, Negrato CA (2014) Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases. Diabetol Metab Syndr 6:80
Maramai S, Benchekroun M, Gabr MT, Yahiaoui S (2020) Multitarget therapeutic strategies for Alzheimer’s disease: review on emerging target combinations. Biomed Res Int 2020:5120230
Di Stefano A, Sozio P, Cocco A, Iannitelli A, Santucci E, Costa M, Pecci L, Nasuti C, Cantalamessa F, Pinnen F (2006) L-Dopa and DA/(R)-α-lipoic acid conjugates as multifunctional codrugs with antioxidant properties. J Med Chem 49:1486–1493
Tu Y, Chen Q, Wang S, Uri A, Yang X, Chu J, Chen J, Luo B, Chen X, Wen S, Pi R (2016) Discovery of lipoic acid-4-phenyl-1H-pyrazole hybrids as novel bifunctional ROCK inhibitors with antioxidant activity. RSC Adv 6:58516–58520
Hensel N, Rademacher S, Claus P (2015) Chatting with the neighbors: crosstalk between Rho-kinase (ROCK) and other signaling pathways for treatment of neurological disorders. Front Neurosci 9:198
Feng Y, Yin Y, Weiser A, Griffin E, Cameron MD, Lin L, Ruiz C, Schürer SC, Inoue T, Rao PV, Schröter T, Lograsso P (2008) Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. J Med Chem 51:6642–6645
Tsiakitzis K, Papagiouvannis G, Theodosis-Nobelos P, Tziona P, Kourounakis PN, Rekka EA (2017) Synthesis, antioxidant and anti-inflammatoy effects of antioxidant acid amides with GABA and N-Acyl-pyrrolidin-2-ones. Current Chem Biol 11:127–139
Theodosis-Nobelos P, Kourti M, Gavalas A, Rekka EA (2016) Amides of non-steroidal anti-inflammatory drugs with thiomorpholine can yield hypolipidemic agents with improved anti-inflammatory activity. Bioorg Med Chem Lett 26:910–913
Wood WG, Li L, Müller WE, Eckert GP (2014) Cholesterol as a causative factor in Alzheimer’s disease: a debatable hypothesis. J Neurochem 129:559–572
Zulkhairi A, Zaiton Z, Jamaluddin M, Sharida F, Mohd TH, Hasnah B, Nazmi HM, Khairul O, Zanariyah A (2008) Alpha lipoic acid possess dual antioxidant and lipid lowering properties in atherosclerotic-induced New Zealand White rabbit. Biomed Pharmacother 62:716–722
Theodosis-Nobelos P, Kourounakis PΝ, Rekka EA (2017) Anti-inflammatory and hypolipidemic effect of novel conjugates with trolox and other antioxidant acids. Med Chem 13:214–225
Jalili-Baleh L, Forootanfar H, Küçükkılınç TT, Nadri H, Abdolahi Z, Ameri A, Jafari M, Ayazgok B, Baeeri M, Rahimifard M, Abbas Bukhari SN, Abdollahi M, Ganjali MR, Emami S, Khoobi M, Foroumadi A (2018) Design, synthesis and evaluation of novel multi-target-directed ligands for treatment of Alzheimer’s disease based on coumarin and lipoic acid scaffolds. Eur J Med Chem 152:600–614
Sozio P, D’Aurizio E, Iannitelli A, Cataldi A, Zara S, Cantalamessa F, Nasuti C, Di Stefano A (2010) Ibuprofen and lipoic acid diamides as codrugs with neuroprotective activity. Arch Pharm 343:133–142
Rosini M, Andrisano V, Bartolini M, Bolognesi ML, Hrelia P, Minarini A, Tarozzi A, Melchiorre C (2005) Rational approach to discover multipotent anti-Alzheimer drugs. J Med Chem 48:360–363
Khanam H, Ali A, Asif M, Shamsuzzaman AA (2016) Neurodegenerative diseases linked to misfolded proteins and their therapeutic approaches: a review. Eur J Med Chem 124:1121–1141
Bartolini M, Bertucci C, Cavrini V, Andrisano V (2003) Amyloid aggregation induced by human acetylcholinesterase: inhibition studies. Biochem Pharmacol 65:407–416
Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, Alfredo Martínez J, Moreno-Aliaga MJ (2013) Effects of lipoic acid on AMPK and adiponectin in adipose tissue of low- and high-fat-fed rats. Eur J Nutr 52:779–787
Ratliff JC, Palmese LB, Reutenauer EL, Tek C (2013) An open-label pilot trial of alpha-lipoic acid for weight loss in patients with schizophrenia without diabetes. Clin Schizophr Relat Psychoses 7:1–13
Xiao C, Giacca A, Lewis GF (2011) Short-term oral α-lipoic acid does not prevent lipid-induced dysregulation of glucose homeostasis in obese and overweight nondiabetic men. Am J Physiol Endocrinol Metab 301:E736–E741
Jung TS, Kim SK, Shin HJ, Jeon BT, Hahm JR, Roh GS (2012) α-lipoic acid prevents non-alcoholic fatty liver disease in OLETF rats. Liver Int 32:1565–1573
Hosseinpour-Arjmand S, Amirkhizi F, Ebrahimi-Mameghani M (2019) The effect of alpha-lipoic acid on inflammatory markers and body composition in obese patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial. J Clin Pharm Ther 44:258–267
Goughari AS, Mazhari S, Pourrahimi AM, Sadeghi MM, Nakhaee N (2015) Associations between components of metabolic syndrome and cognition in patients with schizophrenia. J Psychiatr Pract 21:190–197
Kim NW, Song YM, Kim E, Cho HS, Cheon KA, Kim SJ, Park JY (2016) Adjunctive α-lipoic acid reduces weight gain compared with placebo at 12 weeks in schizophrenic patients treated with atypical antipsychotics: a double-blind randomized placebo-controlled study. Int Clin Psychopharmacol 31:265–274
Bilska-Wilkosz A, Iciek M, Kowalczyk-Pachel D, Górny M, Sokołowska-Jeżewicz M, Włodek L (2017) Lipoic acid as a possible pharmacological source of hydrogen sulfide/sulfane sulfur. Molecules 22:388
Mikami Y, Shibuya N, Kimura Y, Nagahara N, Ogasawara Y, Kimura H (2011) Thioredoxin and dihydrolipoic acid are required for 3-mercaptopyruvate sulfurtransferase to produce hydrogen sulfide. Biochem J 439:479–485
Qiu X, Liu K, Xiao L, Jin S, Dong J, Teng X, Guo Q, Chen Y, Wu Y (2018) Alpha-lipoic acid regulates the autophagy of vascular smooth muscle cells in diabetes by elevating hydrogen sulfide level. Biochim Biophys Acta Mol Basis Dis 1864:3723–3738
Dudek M, Bilska-Wilkosz A, Knutelska J, Mogilski S, Bednarski M, Zygmunt M, Iciek M, Sapa J, Bugajski D, Filipek B, Włodek L (2013) Are anti-inflammatory properties of lipoic acid associated with the formation of hydrogen sulfide? Pharmacol Rep 65:1018–1024
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PT-N and ER had the idea for this article, PT-N and GP performed the literature search and data collection. PT-N and PT wrote the first draft of the manuscript and ER critically revised the manuscript.
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Theodosis-Nobelos, P., Papagiouvannis, G., Tziona, P. et al. Lipoic acid. Kinetics and pluripotent biological properties and derivatives. Mol Biol Rep 48, 6539–6550 (2021). https://doi.org/10.1007/s11033-021-06643-z
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DOI: https://doi.org/10.1007/s11033-021-06643-z