Antidyslipidemic and antioxidant effects of novel Lupeol-derived chalcones.
A series of Lupeol-based chalcones have been synthesized aiming to enhance the therapeutic efficacy of parent compound, the novel compounds were evaluated for their antidyslipidemic activity in triton-WR 1339 induced hyperlipidemic rats. Among the ten synthesized chalcones, the most active K4, K8, and K9 reversed the plasma levels of TC by (24, 25, 27 %), phospholipid by (25, 26, 25 %) and triacylglycerol by (27, 24, 24 %) respectively. In addition, the compounds showed significant in vitro antioxidant activity. The lipid lowering activity of these compounds were mediated through lipoprotein lipase activation (12-21 %) and enhanced post-heparin lipolytic activity (15-16 %). The compounds also displayed noteworthy inhibitory effect on 3-hydroxy-3-methyl-glutaryl reductase activity (in vitro). The in vitro effect of the most active compounds on MDI-induced adipogenesis using 3T3-L1 preadipocytes at 10 and 20 μM concentrations showed significant inhibition (20-32 %) of adipogenesis.
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow, 226 001, India.
Shishir
S
Srivastava
Ravi
R
Sonkar
Sunil Kumar
SK
Mishra
Avinash
A
Tiwari
Vishal M
VM
Balaramnavar
Vishal
V
Balramnavar
Snober
S
Mir
Gitika
G
Bhatia
Anil K
AK
Saxena
Vijai
V
Lakshmi
D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D047188:Chalcones / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006949:Hyperlipidemias / Q000188:drug therapy; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood*; D008297:Male; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes / Q000737:chemistry*; D024301:Plant Bark / Q000737:chemistry; D051381:Rats; D000094042:Lupanes
D000975:Antioxidants; D047188:Chalcones; D008055:Lipids; D053978:Pentacyclic Triterpenes; C010480:lupeol; D000094042:Lupanes