Arctigenin protects cultured cortical neurons from glutamate‐induced neurodegeneration by binding to kainate receptor

Abstract

We previously reported that arctigenin, a lignan isolated from the bark of Torreya nucifera, showed significant neuroprotective activity against glutamate-induced toxicity in primary cultured rat cortical cells. In this study, the mode of action of arctigenin was investigated using primary cultures of rat cortical cells as an in vitro system. Arctigenin significantly attenuated glutamate-induced neurotoxicity when added prior to or after an excitotoxic glutamate challenge. The lignan protected cultured neuronal cells more selectively from neurotoxicity induced by kainic acid than by N-methyl-D-aspartate. The binding of [(3)H]-kainate to its receptors was significantly inhibited by arctigenin in a competitive manner. Furthermore, arctigenin directly scavenged free radicals generated by excess glutamate and successfully reduced the level of cellular peroxide in cultured neurons. These results suggest that arctigenin exerted significant neuroprotective effects on glutamate-injured primary cultures of rat cortical cells by directly binding to kainic acid receptors and partly scavenging of free radicals.

Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors

“…A previous study suggested a direct interaction between arctigenin and kainate receptors in cultured cerebrocortical neurons (Jang et al, 2002). This study demonstrated the neuroprotective effect of arctigenin in an in vitro cell culture system using kainate evoked neurodegeneration.…”

“…Lignans are important biologically active phenolic compounds related to lignin, produced in different plants, for example in tribe Cynareae, such as Arctium, (Boldizsár et al, 2010a), Cirsium (Boldizsár et al, 2010b) species, Forsythia (Maiada et al, 1990) or Torreya (Zhao et al, 1999) (Jang et al, 2002). However, the direct effects of arctigenin on normal neuronal activity have not been established.…”

Isochaihulactone protects PC12 cell against H2O2 induced oxidative stress and exerts the potent anti-aging effects in D-galactose aging mouse model

“…Isochaihulactone (also known as K8) is a lignan compound that was identified in acetone extracts of Nan-Chai-Hu and shows antitumor activity against A549 cells in vitro and in vivo [25,26] . Lignan compounds (eg, sesamin, sesamolin) have been reported to act as neuroprotective agents against oxidative injury and excitotoxicity [27][28][29][30] . Lignans can also inhibit lipopolysaccharide-inducible COX-2 expression in macrophages [31] .…”

Neuroprotective phenolics in medicinal plants

“…Among the isolated compounds, arctigenin effectively inhibited the receptor binding of [ 3 H]-kainate in a competitive manner. Furthermore, it directly scavenged free radicals generated by excess glutamate (Jang et al, 2002).…”