R-α-Lipoic Acid Conjugated to d-α-Tocopherol Polyethylene Glycol 1000 Succinate: Synthesis, Characterization, and Effect on Antiseizure Activity

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 halflife. 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 1 H and 13 C 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.

α-Lipoic Acid Alleviated Fluoride-Induced Hepatocyte Injury via Inhibiting Ferroptosis

“…α-Lipoic acid is the most powerful natural antioxidant found so far . In addition, α-lipoic acid is widely distributed in animal cells, but its content is limited and it is not easy to store, so it should be properly supplemented if necessary .…”

Protective Effect of Orbitides from Linseed (Linum usitatissimum L.) against Ultraviolet B‐induced Photoaging in Zebrafish

“…Determination the content of protein carbonyl. The protein carbonyl content adapted from the previous research method (27). 200 μL of supernatant was mixed with the same volume of 10 mM dinitrophenyl hydrazine (DNPH) solution.…”

“…ROS-induced protein oxidative damage can result in conformation changes and unfolding and then further lead to protein inactivation and cross-linking and ultimately cause body aging (1). Therefore, protein carbonyl level, thiol level and protein surface hydrophobicity were detected to evaluate the protein oxidation in UVBtreated zebrafish (1,27,29).…”