Neuroprotective effects of Fomes officinalis Ames polysaccharides on Aβ25-35-induced cytotoxicity in PC12 cells through suppression of mitochondria-mediated apoptotic pathway.

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Aggregation of Aβ is a pathological hallmark of Alzheimer's disease (AD). The purpose of this study was to identify the protective roles of different polysaccharide components in Fomes officinalis Ames polysaccharides (FOAPs) against Aβ25-35-induced neurotoxicity in PC12 cells. Different doses of FOAPs components (i.e. FOAPs-a and FOAPs-b) were added to PC12 cells about 2h before β-amyloid protein fragment 25-35 (Aβ25-35) exposure. The AD cellular model of PC12 cells was established using Aβ25-35. Then the PC12 cells were divided into 9 groups including: control group, Donepezil hydrochloride (DHCL) group, model group treated using 40μM Aβ25-35, followed by FOAPs-a and FOAPs-b interference (50, 100 and 200μg/mL). The mitochondrial reactive oxygen species (ROS), ATP, superoxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH) and mitochondrial membrane potential (MMP) were determined by commercial kits. The Cytochrome C, Bcl-2 and Bax expressions in the mitochondria and cytosol was determined by using Western blot analysis. FOAPs-a and FOAPs-b could significantly inhibit the LDH release, MDA level and the over accumulation of ROS induced by Aβ25-35 in PC12 cells in a dose-dependent manner. They could also effectively prevent Aβ25-35-stimulated cytotoxicity, which involved in attenuating cell apoptosis, increasing the ratio of Bcl-2/Bax and inhibiting Cytochrome C release from mitochondria to cytosol in PC12 cells. Moreover, FOAPs-a and FOAPs-b significantly alleviated mitochondrial dysfunction by regulating the MMP, as well as promoting the mitochondrial ATP synthesis. FOAPs-a and FOAPs-b played neuroprotective roles against Aβ25-35-induced cytotoxicity in PC12 cells through suppressing the mitochondria-mediated apoptotic pathway.