The aqueous extract from anti-aging Ganoderma lucidum inhibits beta-amyloid peptide-induced neurotoxicity

Abstract

Ganoderma lucidum (Lingzhi) is an anti-aging oriental medicine that has been used for centuries in China to promote health. Numerous studies have reported the immunoregulatory and anti-tumor activities of G. lucidum. Although G. lucidum exhibits a wide array of effects on cancer and immune system, only few biological effects are known in the nervous system. We, therefore, take initiative to investigate its potential neuroprotective effects. Our results demonstrated that aqueous extract of G. lucidum exhibited neuroprotective effects against β-amyloid peptide (Aβ), 6-hydroxdopamine (6-OHDA) and staurosporine in differentiated human neuroblastoma SH-SY5Y. Since Aβ peptide plays significant roles in pathogenesis of Alzheimer’s disease, we have further investigated the neuroprotective effects of G. lucidum against Aβ toxicity by using primary cultures of cortical neurons. Pre-treatment of G. lucidum aqueous extract significantly attenuated Aβ-induced DEVD- (caspase-3 like) cleavage activities in a dose-dependent manner. In addition, aqueous extract of G. lucidum attenuated Aβ-induced synaptotoxicity by examining pre-synaptic synaptophysin immunoreactivity. Furthermore, treatment of G. lucidum aqueous extract attenuated the phosphorylation of c-Jun N-terminal kinase (JNK), c-Jun II and p38 MAPK in Aβ-stressed neurons. Together our previous study on anti-aging oriental medicine, G. lucidum is another example exhibiting neuroprotective effects and potential to be developed as neuroprotective agent.