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. Georg Thieme Verlag KG Stuttgart . New York.