Andrographolide, a major component of Andrographis paniculata leaves, has the neuroprotective effects on glutamate-induced HT22 cell death

Andrographis paniculata (AP) is a traditional herbal medicine that is used for the treatment of inflammation-related disorders, dyspepsia, and diarrhea. Recently, the biological effects of AP on cancer, microbial infections, cardiovascular disease, and inflammation were reported. However, neuroprotective actions of AP during glutamate-induced oxidative stress have not been investigated. In this study, we isolated andrographolide (AG) as an active compound from the ethanolic extract of AP leaves, and evaluated its neuroprotective mechanisms using glutamate-treated HT22 mouse hippocampal neuronal cells. Five mM glutamate reduced cell survival significantly to 55.90 +/- 2.16%. However, 5 mu M AG restored cell viability to 102.19 +/- 13.98%. AG decreased the early apoptosis by inhibiting Ca2+ influx, intracellular reactive oxygen species production, and lipid peroxidation. Moreover, AG regulated the levels of Bcl-2, Bid, Bax, and apoptosis-inducing factor. AG also inhibited the phosphorylation of mitogen activated protein kinases including p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. (C) 2014 Elsevier Ltd. All rights reserved.