Biochemical and clinical relevance of alpha lipoic acid: antioxidant and anti-inflammatory activity, molecular pathways and therapeutic potential

Abstract

Background

The molecular nature of lipoic acid (LA) clarifies its capability of taking part to a variety of biochemical reactions where redox state is meaningful. The pivotal action of LA is the antioxidant activity due to its ability to scavenge and inactivate free radicals. Furthermore, LA has been shown to chelate toxic metals both directly and indirectly by its capability to enhance intracellular glutathione (GSH) levels. This last property is due to its ability to interact with GSH and recycle endogenous GSH. LA exhibits significant antioxidant activity protecting against oxidative damage in several diseases, including neurodegenerative disorders. Interestingly, LA is unique among natural antioxidants for its capability to satisfy a lot of requirements, making it a potentially highly effective therapeutic agent for many conditions related with oxidative damage. In particular, there are evidences showing that LA has therapeutic activity in lowering glucose levels in diabetic conditions. Similarly, LA supplementation has multiple beneficial effects on the regression of the mitochondrial function and on oxidative stress associated with several diseases and aging.

Aim

The aim of the present review is to describe the molecular mechanisms underlying the beneficial effects of LA under various experimental conditions and disease and how to exploit such effect for clinical purposes.

Conclusion

LA has pleiotropic effects in different pathways related with several diseases, its use as a potential therapeutic agent is very promising.

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Abbreviations

LA:

Lipoic acid

DHLA:

Dihydrolipoic acid

R-LA or (+)LA:

R-enantiomer lipoic acid

S-LA or (-)LA:

S-enantiomer lipoic acid

(±)LA:

Raceme lipoic acid

ROS:

Reactive oxygen species

RNS:

Reactive nitrogen species

SOD:

Superoxide dismutase

GSH:

Glutathione

GSSG:

Disulfide form of glutathione

MAPK:

Mitogen activated protein Kinases

PI3-K:

Phosphatidyl inositide 3-kinase

αGPC:

l-α-glycerylphosphorylcholine

GPCR:

G protein coupled receptor

ERK:

Extracellular regulated Kinases

JNK:

c-Jun N-terminal kinase

AKT:

The protein kinase B

NF-kB:

Nuclear factor-KB

IGF-1:

Insulin-like growth factor-1

IR:

Insulin receptor

IRS1:

Insulin receptor substrate 1

IRS-1:

Insulin receptor substrate-1

AMPK:

5′ Adenosine monophosphate-activated protein kinase

PTP1B:

Cellular protein tyrosine phosphatases

LKB-1:

Liver kinase B1

CaMKK:

Ca/calmodulin dependent protein kinase

PGC-1-alpha:

Proliferator activated receptor-gamma coactivator-1alpha

EAE:

Experimental autoimmune encephalomyelitis

AD:

Alzheimer’s disease

AChE:

Acetylcholinesterase

AGEs:

Advanced glycation end product

HNE:

4-Hydroxy-2-nonenal

PKC:

Protein kinase C

GLUT:

Glucose transport protein

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Acknowledgements

The authors acknowledged pharmaceutical MDM S.p.A. Via Volturno, 29/b—20900 Monza (MB), Italy, e-mail: mdm@mdmspa.com.

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All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: RA and VB. Managing the literature searches: DT, SG, CG, DT. Drafting of the manuscript: RA and VB. Critical revision of the manuscript: DT, CG, CDA, GL, GLV, FA, RA and VB. Administrative and technical support: CG, DT. Supervision of the study: DT, RA and VB. Approving the final draft of manuscript: all the authors.

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Correspondence to Roberto Avola.

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All authors declare no conflict of interest.

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Responsible Editor: John Di Battista.

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Tibullo, D., Li Volti, G., Giallongo, C. et al. Biochemical and clinical relevance of alpha lipoic acid: antioxidant and anti-inflammatory activity, molecular pathways and therapeutic potential. Inflamm. Res. 66, 947–959 (2017). https://doi.org/10.1007/s00011-017-1079-6

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Keywords

  • Alpha lipoic acid
  • Antioxidant
  • Chelation
  • Free radical scavenger
  • Glutathione
  • Inflammation
  • Therapeutic potential