ABSTRACT
Nine previously undescribed butyrolactone and sesquiterpene derivatives, named cyclopentanone A (1), subamolides F and G (2 and 3), secosubamolide F (4), rupestonic acids J - L (5-7), linderaguaianols A and B (8 and 9), together with six known ones 10-15 were isolated from the roots of Lindera glauca. Their structures, including their absolute configurations were elucidated by extensive spectroscopic analysis, quantum chemical calculations, and Mo2(AcO)4-induced circular dichroism. Compound 1 that possessed a unique five-membered cyclopentane skeleton with a side chain was rarely found from natural sources. The biogenetic pathway for 1-4 was postulated. Secosubamolide F (4) inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 cells with IC50 value of 1.73 ± 0.18 µM and also significantly suppressed the production of iNOS. The binding interactions between 4 and iNOS were investigated using docking analyses.
Subject(s)
Enzyme Inhibitors/pharmacology , Lindera/chemistry , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide/antagonists & inhibitors , Plant Roots/chemistry , Sesquiterpenes/pharmacology , Animals , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/metabolism , RAW 264.7 Cells , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Structure-Activity RelationshipABSTRACT
Heat shock protein 32 (HSP32) is a stress response protein that can be induced by heat stress in the liver, and its induction can act as an important cellular defence mechanism against heat-induced liver injury. To investigate the functional role of HSP32 in protecting liver tissue against heat stress in mice and the mechanism by which it achieves this protective effect, HSP32 expression and carbon monoxide (CO) contents in a model of mice subjected to acute, transient heat exposure were examined. Furthermore, functional and histological parameters of liver damage and the possible involvement of oxidative stress to induce oxidative deterioration of liver functions and caspase-3 expression were also investigated in this study. We found that heat treatment of mice produced severe hepatic injury, whereas upregulation of HSP32 with hemin pretreatment prevented mice from liver damage. In contrast, addition of Sn-protoporphyrin (SnPP) to inhibit HSP32 expression completely reversed its hepatoprotective effect. It is concluded that upregulation of HSP32 by hemin could alleviate acute heat-induced hepatocellular damage in mice, and its by-product CO seems to play a more important role in hepatoprotective mechanism.
