PUBLICATION
R-α-Lipoic Acid Conjugated to d-α-Tocopherol Polyethylene Glycol 1000 Succinate: Synthesis, Characterization, and Effect on Antiseizure Activity
- Authors
- Ruchika, ., Kumari, S., Dhiman, P., Singh, D., Saneja, A.
- ID
- ZDB-PUB-220622-25
- Date
- 2022
- Source
- Journal of Agricultural and Food Chemistry 70(25): 7674-7682 (Journal)
- Registered Authors
- Keywords
- anticonvulsion activity, epilepsy, lipoic acid, tocopherol poly(ethylene glycol) 1000 succinate, zebrafish
- MeSH Terms
-
- Animals
- Polyethylene Glycols/chemistry
- Spectroscopy, Fourier Transform Infrared
- Succinates
- Thioctic Acid*/pharmacology
- Vitamin E/chemistry
- Vitamin E/pharmacology
- Zebrafish
- alpha-Tocopherol/pharmacology
- PubMed
- 35713421 Full text @ J. Agric. Food Chem.
Citation
Ruchika, ., Kumari, S., Dhiman, P., Singh, D., Saneja, A. (2022) R-α-Lipoic Acid Conjugated to d-α-Tocopherol Polyethylene Glycol 1000 Succinate: Synthesis, Characterization, and Effect on Antiseizure Activity. Journal of Agricultural and Food Chemistry. 70(25):7674-7682.
Abstract
α-Lipoic acid (LA), a dithiol micronutrient, acts as a vital cofactor in various cellular catabolic reactions and is also known as a universal antioxidant. The therapeutic efficacy of LA is compromised by a poor aqueous solubility as well as a short half-life. In the present study, LA was conjugated to d-α-tocopherol polyethylene glycol succinate (TPGS) using carbodiimideacid-alcohol coupling reaction. The synthesized conjugate (TPGS-LA) was characterized using 1H and 13C nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), UV-vis spectroscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The TPGS-LA conjugate was demonstrated to be biocompatible and to have better anticonvulsion activity as compared to native LA in pentylenetetrazol (PTZ)-induced convulsions in zebrafish. Moreover, zebrafish larvae pretreated with TPGS-LA conjugate demonstrated a significant (p < 0.05) reduction of protein carbonylation levels and downregulation of c-fos expression during seizures as compared to native LA. Conclusively, the present findings demonstrate that the TPGS-LA conjugate can be a promising approach for the delivery of LA.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping