Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention

Abstract

Alpha-lipoic acid is an organic, sulfate-based compound produced by plants, humans, and animals. As a potent antioxidant and a natural dithiol compound, it performs a crucial role in mitochondrial bioenergetic reactions. A healthy human body, on the other hand, can synthesize enough α-lipoic acid to scavenge reactive oxygen species and increase endogenous antioxidants; however, the amount of α-lipoic acid inside the body decreases significantly with age, resulting in endothelial dysfunction. Molecular orbital energy and spin density analysis indicate that the sulfhydryl (-SH) group of molecules has the greatest electron donating activity, which would be responsible for the antioxidant potential and free radical scavenging activity. α-Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E. α-Lipoic acid enantiomers and its reduced form have antioxidant, cognitive, cardiovascular, detoxifying, anti-aging, dietary supplement, anti-cancer, neuroprotective, antimicrobial, and anti-inflammatory properties. α-Lipoic acid has cytotoxic and antiproliferative effects on several cancers, including polycystic ovarian syndrome. It also has usefulness in the context of female and male infertility. Although α-lipoic acid has numerous clinical applications, the majority of them stem from its antioxidant properties; however, its bioavailability in its pure form is low (approximately 30%). However, nanoformulations have shown promise in this regard. The proton affinity and electron donating activity, as a redox-active agent, would be responsible for the antioxidant potential and free radical scavenging activity of the molecule. This review discusses the most recent clinical data on α-lipoic acid in the prevention, management, and treatment of a variety of diseases, including coronavirus disease 2019. Based on current evidence, the preclinical and clinical potential of this molecule is discussed. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s43450-023-00370-1.

Recent Advances in Electrochemical Sensors for Sulfur-Containing Antioxidants

“…On the other hand, it is widely used as part of dietary supplements and pharmaceutical dosage forms applied in medicine. α-Lipoic acid has multi-beneficial functions in the human organism [ 32 ], i.e.,…”

“…Biological aspects of sulfur-containing antioxidant actions, their metabolism, and implementation in diseases pathogenesis are discussed in detail in reviews [ 10 , 16 , 19 , 22 , 24 , 25 , 30 , 31 , 32 ].…”

Reactivity of oxidants towards phenyl and benzyl substituted 5-selanylpentanoic acids: radiolytic and theoretical insights

“…13,14 Furthermore, it is worth noting that the carboxylic group, found in various naturally occurring antioxidants such as lipoic acid, plays a significant role in their activity. [17][18][19] Recent investigations have revealed that compounds derived from pentanoic acid demonstrate heightened neuroprotective capabilities, attributed to their ability to mitigate oxidative stress. 20 While earlier studies have extensively explored the one-electron oxidations of organosulfur compounds, both aliphatic and aromatic, there is a scarcity of reports on organoselenium compounds.…”

Quantification of alpha-lipoic acid in pharmaceutical samples using Pd(II) catalyzed ligand substitution reaction in SLS micellar medium

“…The body naturally produces alpha-lipoic acid (ALA), often referred to as thioctic acid (TA), which is necessary for the operation of certain oxidative metabolic enzymes [1,2]. Its main function is to use oxygen to turn blood sugar (glucose) into energy [3,4].…”