Hirsutine, an indole alkaloid of Uncaria rhynchophylla, inhibits inflammation‐mediated neurotoxicity and microglial activation

Abstract

Uncaria rhynchophylla is a traditional oriental herb that has especially been used for treatment of disorders of the cardiovascular and central nervous systems. Hirsutine, one of the major indole alkaloids of Uncaria rhynchophylla has been shown to have neuroprotective potential. The specific aim of this study was to examine the efficacy of hirsutine in the repression of inflammation‐induced neurotoxicity and microglial cell activation. In organotypic hippocampal slice cultures, hirsutine blocked lipopolysaccharide (LPS)‐mediated hippocampal cell death and productions of nitric oxide (NO), prostaglandin (PG) E2 and interleukin (IL)‐1β. Hirsutine was shown to effectively inhibit LPS‐induced NO release from primary cultured rat brain microglia. This compound reduced the LPS‐stimulated productions of PGE2 and intracellular reactive oxygen species. Hirsutine significantly decreased LPS‐induced phosphorylation of the mitogen‐activated protein kinases and Akt signaling proteins. In conclusion, hirsutine reduces the productions of various neurotoxic factors in activated microglial cells, and possesses neuroprotective activity in a model of inflammation‐induced neurotoxicity.