6-Hydroxycleroda-3,13-dien-15,16-olide protects neuronal cells from lipopolysaccharide-induced neurotoxicity through the inhibition of microglia-mediated inflammation.
Polyalthia longifolia var. pendula is used as an antipyretic agent in indigenous systems of medicine. Microglia-mediated inflammation plays an important role in the pathway leading to neuronal cell death in a number of neurodegenerative diseases. The aim of this study was to investigate the effects of 6-hydroxycleroda-3,13-dien-15,16-olide (PL3) extracted from Polyalthia longifolia var. pendula on lipopolysaccharide(LPS)-induced inflammation in microglia-like HAPI cells and primary microglia cultures. In microglia-neuron co-cultures, LPS decreased the cell viability of neuroblastoma SH-SY5Y cells. LPS-induced cell death was attenuated by the NOS inhibitor, L-NAME, the COX-2 inhibitor, NS-398 or the NADPH oxidase inhibitor, DPI, respectively. In LPS-treated microglia cells, PL3 decreased the expression of iNOS, COX-2, gp91 (phox), and NF- kappaBp65, the degradation of I kappaB alpha, and the production of NO, PGE (2), iROS, and TNF- alpha. PL3 also enhanced the expression of HO-1, a cytoprotective and anti-inflammatory enzyme. Moreover, PL3 reduced LPS-activated microglia-induced cell death. The present results suggest that PL3 inhibits microglia-mediated inflammation and inflammation-related neuronal cell death. Therefore, PL3 has potential use for the treatment of inflammation-related neurodegenerative diseases.
Shih
Yu-Tzu
YT
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hsu
Ya-Yun
YY
Chang
Fang-Rong
FR
Wu
Yang-Chang
YC
Lo
Yi-Ching
YC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D017628:Microglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D031044:Polyalthia / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010936:Plant Extracts; C072581:16-hydroxycleroda-3,13(14)-dien-15,16-olide