Alpha-lipoic acid: molecular mechanisms and therapeutic potential in diabetes

Abstract

Diabetes is a chronic metabolic disease with a high prevalence worldwide. Diabetes and insulin resistance are associated with the development of cardiovascular and nervous diseases. The development of these disorders reflects complex pathological processes in which the oxidative stress caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) plays a pivotal role. It is widely accepted that diabetes impairs endothelial nitric oxide synthase (eNOS) activity and increases the production of ROS, thus resulting in diminished NO bioavailability and increased oxidative stress. Alpha-lipoic acid (LA) possesses beneficial effects both in the prevention and in the treatment of diabetes. LA is a potent antioxidant with insulin-mimetic and anti-inflammatory activity. LA in the diet is quickly absorbed, transported to the intracellular compartments, and reduced to dihydrolipoic acid (DHLA) under the action of enzymes. LA, which plays an essential role in mitochondrial bioenergetic reactions, has drawn considerable attention as an antioxidant for use in managing diabetic complications such as retinopathy, neuropathy and other vascular diseases.

A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients

“…It has been largely reported that diabetes impairs endothelial nitric oxide synthase (eNOS) activity, thus increasing ROS production, with a consequent reduction of NO bioavailability. α-lipoic acid has shown beneficial effects both in the prevention and in the treatment of diabetes because of its insulin-mimetic and anti-inflammatory action; it is also involved in mitochondrial bioenergetic reactions [11]. The positive effects of α-lipoic acid on oxidative stress parameters have been shown by our study: α-lipoic acid increased SOD, an enzyme with the role of commuting highly reactive O 2− into H 2 O 2 , which is subsequently reduced in H 2 O by mitochondrial glutathione peroxidase and catalase [12].…”

Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases

“…[Stacpoole, 2012]. ALA is present in almost all foodtypes [Li, 2015] and although it is readily digested, absorbed, and transported to tissues, including the brain [Carlson et al, 2007;Papanas and Ziegler, 2015;Rochette et al, 2015], the amounts available from diet are low [Li, 2015;D€ orsam and Fahrer, 2016]. In most prokaryotic and eukaryotic microorganisms, plant and animal mitochondria, and plant plastids, ALA is enzymatically synthesized endogenously from octanoate [Spalding et al, 2010;Pashaj et al, 2015;Zhang et al, 2015].…”

Overproduction of α-Lipoic Acid by Gene Manipulated Escherichia coli

“…It exists in water soluble oxidized and reduced forms [1]. As an antioxidant, the beneficial effects of LA have been shown on three fronts: (1) scavenging free radicals and reactive oxygen species; (2) chelating metal ions; (3) the regeneration of other antioxidants, such as vitamin E, vitamin C and glutathione [2], which have applications in the prevention and treatment of diabetes (including chronic complications), cerebral and neuro-degenerative diseases, radiation injury, ischemia reperfusion injury, and AIDS [3–6]. Furthermore, it has recently been reported that LA alone or in combination with paclitaxel can inhibit NF-κB expression and thus, inhibit breast cancer cell proliferation [7].…”