Hypolipidemic effect of novel 2,5-bis(4-hydroxybenzylidenamino)-1,3,4-thiadiazole as potential peroxisome proliferation-activated receptor-alpha agonist in acute hyperlipidemic rat model
MOLECULAR AND CELLULAR BIOCHEMISTRY
Authors: Hamadneh, Lama A.; Sabbah, Dima A.; Hikmat, Suhair J.; Al-Samad, Luma A.; Hasan, Mariam; Al-Qirim, Tariq M.; Hamadneh, Imad M.; Al-Dujaili, Ammar H.
Abstract
The development of new antihyperlipidemic agents with higher potency and lower side effects is of high priority. In this study, 1,3,4 thiadiazole Schiff base derivatives were synthesized as potential peroxisome proliferation-activated receptor-alpha (PPAR alpha) agonists and characterized using elemental analysis, FTIR, H-1-NMR, C-13-NMR and mass spectroscopy and then tested for their hypolipidemic activity in Triton WR-1339-induced acute hyperlipidemic rat model in comparison with bezafibrate. The compounds showed significant hypolipidemic activity. Induced fit docking showed that the compounds are potential activators of PPAR alpha with binding scores-8.00Kcal/mol for 2,5-bis(4-hydroxybenzylidenamino)-1,3,4-thiadiazole. PCR array analysis showed an increase in the expression of several genes involved in lipid metabolism through mitochondrial fatty acid beta oxidation and are part of PPAR alpha signaling pathway including Acsm3, Fabp4 and Hmgcs1. Gene expression of Lrp12 and Lrp1b involved in LDL uptake by liver cells and Cyp7a1 involved in cholesterol catabolism were also found to be upregulated.
LRP12 is associated with malignancies in liver cancer
TRANSPLANTATION
Authors: Yan, Y.; Wang, W.
Abstract
COA
Publication 
Loading ......
