Lipoic acid and carvedilol promote remyelination in cuprizone model

[NHE]

Remyelinating activities of Carvedilol or alpha lipoic acid in the Cuprizone-Induced rat model of demyelination
Int Immunopharmacol. 2023 May:118:110125.

Multiple sclerosis (MS) is a complex and multifactorial neurodegenerative disease with unknown etiology, MS is featured by multifocal demyelinated lesions distributed throughout the brain. It is assumed to result from an interaction between genetic and environmental factors, including nutrition. Therefore, different therapeutic approaches are aiming to stimulate remyelination which could be defined as an endogenous regeneration and repair of myelin in the central nervous system. Carvedilol is an adrenergic receptor antagonist. Alpha lipoic acid (ALA) is a well-known antioxidant. Herein, we investigated the remyelination potential of Carvedilol or ALA post-Cuprizone (CPZ) intoxication. Carvedilol or ALA (20 mg/kg/d) was administrated orally for two weeks at the end of the five weeks of CPZ (0.6%) administration. CPZ provoked demyelination, enhanced oxidative stress, and stimulated neuroinflammation. Histological investigation of CPZ-induced brains showed obvious demyelination in the corpus callosum (CC). Both Carvedilol and ALA demonstrated remyelinating activities, with corresponding upregulation of the expression of MBP and PLP, the major myelin proteins, downregulation of the expression of TNF-α and MMP-9, and decrement of serum IFN-γ levels. Moreover, both Carvedilol and ALA alleviated oxidative stress, and ameliorated muscle fatigue. This study highlights the neurotherapeutic potential of Carvedilol or ALA in CPZ-induced demyelination, and offers a better model for the exploring of neuroregenerative strategies. The current study is the first to demonstrate a pro-remyelinating activity for Carvedilol, as compared to ALA, which might represent a potential additive benefit in halting demyelination and alleviating neurotoxicity. However, we could declare that Carvedilol showed a lower neuroprotective potential than ALA.

[DIM]

20 mg/kg/d is too much ALA and costs a lot.
They don't mention what type of ALA they use.
We all know that sodium salt of ALA especially in caps form is more stable, less sensitive to heat and light and has increased bioavailability, I don't know by how much though!

[NHE]

20 mg/kg/d is too much ALA and costs a lot.
They don't mention what type of ALA they use.

Unless a paper specifies R-Lipoic Acid or Na-R-Lipoate, I think it's safe to assume that Alpha Lipoic Acid refers to racemic R/S-Lipoic Acid.

[DIM]

20 mg/kg/d is too much ALA and costs a lot.
They don't mention what type of ALA they use.

Unless a paper specifies R-Lipoic Acid or Na-R-Lipoate, I think it's safe to assume that Alpha Lipoic Acid refers to racemic R/S-Lipoic Acid.

I assume with less quantity of Na-R-Lipoate we have the same results due to increased bioavailability

[NHE]

Here's a study I posted a while back. It found increased Cmax and AUC for Na-R-Lipoate vs. R-Lopic Acid.

viewtopic.php?t=31875

[DIM]

Here's a study I posted a while back. It found increased Cmax and AUC for Na-R-Lipoate vs. R-Lopic Acid.

viewtopic.php?t=31875

More or less half quantity of Na-R-ALA is needed compared to R-ALA or R/S-ALA, perfect!

[NHE]

More or less half quantity of Na-R-ALA is needed compared to R-ALA or R/S-ALA, perfect!

I would not put R-Lipoic Acid and racemic R/S-Lipoic Acid (aka Alpha Lipoic Acid) in the same basket. The R and S enantiomers are not equivalent. The S enantiomer has a physiological cost associated with it. This situation is common in pharmacodynamics. Please see the following post.

Lipoic Acid: R vs. S

viewtopic.php?p=29715#p29715