α-Lipoic Acid

Names

[ Name ]:
α-Lipoic Acid

[Synonym ]:
(S)-5-(1,2-Dithiolan-3-yl)pentanoic acid
Thioctic acid
5-[(3S)-Dithiolan-3-yl]pentanoic acid
(S)-6,8-Thioctic acid (S)-1,2-Dithiolane-3-pentanoic acid
DL-Thioctic acid
5-(1,2-Dithiolan-3-yl)pentanoic acid
DL-α-Lipoic acid
(±)-α-Lipoic acid
5-(dithiolan-3-yl)pentanoic acid
6,8-Dithiooctanoic acid
MFCD00005474
1,2-Dithiolane-3-pentanoic acid
(±)-1,2-Dithiolane-3-pentanoic acid
(±)-1,2-Dithiolane-3-valeric acid
6,8-Dihydrothioctic acid
lipoic acid
UNII:73Y7P0K73Y
DL-6,8-Thioctic acid
EINECS 214-071-2
α-Lipoic Acid

Biological Activity

[Description]:

α-Lipoic Acid is an antioxidant, which is an essential cofactor of mitochondrial enzyme complexes. α-Lipoic Acid inhibits NF-κB-dependent HIV-1 LTR activation.

[Related Catalog]:

Signaling Pathways >> Anti-infection >> HIV

Signaling Pathways >> Metabolic Enzyme/Protease >> Mitochondrial Metabolism

Natural Products >> Acids and Aldehydes

Research Areas >> Cancer

Research Areas >> Inflammation/Immunology

Research Areas >> Infection

[Target]

NF-κB

HIV

Mitochondrial bioenergetics

[In Vitro]

The long terminal repeat (LTR) of HIV-1 is the target of cellular transcription factors such as NF-κB, and serves as the promoter-enhancer for the viral genome when integrated in host DNA[1]. α-Lipoic Acid (Alpha-Lipoic acid, ALA), a naturally occurring dithiol compound, plays an essential role in mitochondrial bioenergetics. α-Lipoic Acid reduces lipid accumulation in the liver by regulating the transcriptional factors SREBP-1, FoxO1, and Nrf2, and their downstream lipogenic targets via the activation of the SIRT1/LKB1/AMPK pathway. Treatment of cells with α-Lipoic Acid (250, 500 and 1000 μM) significantly increases the NAD+/NADH ratio in HepG2 cells (P<0.05 or P<0.01). Treatment with α-Lipoic Acid (50, 125, 250 and 500 μM) increases SIRT1 activity in HepG2 cells. α-Lipoic Acid (50, 125, 250, 500 and 1000 μM) increases phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) in HepG2 cells in a dose-dependent fashion[1].

[In Vivo]

C57BL/6J mice, divided into four groups, are fed an high-fat diet (HFD) for 24 weeks to induce nonalcoholic fatty liver disease (NAFLD) followed by daily administration of α-Lipoic Acid. Then, the effects of α-Lipoic Acid on hepatic lipid accumulation in long-term HFD-fed mice are assessed. Administration of α-Lipoic Acid (100 mg/kg or 200 mg/kg) markedly reduces visceral fat mass in mice. In addition, α-Lipoic Acid (100 mg/kg or 200 mg/kg) treatment inhibits the appetite and causes a dramatic weight loss (all P<0.05)[1].

[Cell Assay]

The human hepatocellular carcinoma (HepG2) cell line is cultured in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum at 37°C and 5% CO2. HepG2 cells are treated with AMPK inhibitor (CC, 20 μM, 0.5 h), SIRT1 inhibitor (NA, 10 mM, 12 or 24 h), and AMPK activator (AICAR, 2 mM, 1 h), Palmitate (PA, 125 μM, 12 h) and α-Lipoic Acid (250 μM, 6 or 12 h)[1].

[Animal admin]

Mice[1] Male C57BL/6J mice (6-week-old; body weight: 22-24 g) are allowed ad libitum access to normal diet and water for 2 weeks before dividing into four groups (n=8): normal diet (ND) (10% energy from fat), high-fat diet (HFD) (60% energy from fat) and HFD plus α-Lipoic Acid (100 mg/kg or 200 mg/kg). After 24 weeks of treatment, blood samples are collected after the eyeballs of the mice are extracted for serum preparation by centrifugation at 2000×g for 10 min at 4°C. The liver tissues are harvested in liquid nitrogen and stored at -80°C.

[References]

[1]. Xiao L, et al. Activity of the dietary antioxidant ergothioneine in a virus gene-based assay for inhibitors of HIV transcription. Biofactors. 2006;27(1-4):157-65.

[2]. Yang Y, et al. Alpha-lipoic acid improves high-fat diet-induced hepatic steatosis by modulating the transcription factors SREBP-1, FoxO1 and Nrf2 via the SIRT1/LKB1/AMPK pathway. J Nutr Biochem. 2014 Nov;25(11):1207-1217.

[3]. Lei D, et al. Synergistic neuroprotective effect of rasagiline and idebenone against retinal ischemia-reperfusion injury via the Lin28-let-7-Dicer pathway. Oncotarget. 2018 Jan 30;9(15):12137-12153.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
362.5±11.0 °C at 760 mmHg

[ Melting Point ]:
60-62ºC

[ Molecular Formula ]:
C₈H₁₄O₂S₂

[ Molecular Weight ]:
206.326

[ Flash Point ]:
173.0±19.3 °C

[ Exact Mass ]:
206.043518

[ PSA ]:
87.90000

[ LogP ]:
2.16

[ Vapour Pressure ]:
0.0±1.7 mmHg at 25°C

[ Index of Refraction ]:
1.562

[ Storage condition ]:
2-8°C

[ Stability ]:
Stable. Incompatible with strong oxidizing agents.

[ Water Solubility ]:
ethanol: 50 mg/mL | 0.9 g/L (20 ºC)

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: JP1192000

CHEMICAL NAME :: 1,2-Dithiolane-3-valeric acid, (+-)-

CAS REGISTRY NUMBER :: 1077-28-7

BEILSTEIN REFERENCE NO. :: 0081853

LAST UPDATED :: 199612

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C8-H14-O2-S2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 235 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 21,284,1971

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Precautionary Statements ]:
P301 + P312 + P330

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xn: Harmful;

[ Risk Phrases ]:
R22

[ Safety Phrases ]:
37/39-26-24/25-36

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
JP1192000

[ HS Code ]:
2934999090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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