Mulberry Extracts Alleviate Aβ_25–35‐Induced Injury and Change the Gene Expression Profile in PC12 Cells

Abstract

Mulberry, which contained high amounts of anthocyanins, has been used in traditional Chinese medicine. Mulberry fruit extracts (ME) have demonstrated the antioxidant activity and neuroprotection. The study was to investigate the neuroprotective efficacy of ME against β-amyloid 25–35- (Aβ 25–35-) induced PC12 cells injury. Cells preincubated with or without ME (200 μg/mL) for 24 h were treated with Aβ 25–35 (20 μmol/L) for another 24 h. Cell viability was assessed by MTT, gene expression profiles were examined by cDNA microarrays, and RT-PCR were used to confirm the results of microarray assays. ME pretreatment was found to neutralize the cytotoxicity and prevent Aβ 25–35-induced cells injury. Analyses of gene expression profile revealed that genes involving cell adhesion, peptidase activity, cytokine activity, ion binding activity, and angiogenesis regulation were significantly modulated by ME pretreatment. Among those genes, Apaf1, Bace2, and Plcb4 were enriched in the “Alzheimer's disease-reference pathway” and downregulated after ME intervention. RT-PCR results showed that ME preincubation could significantly inhibit Aβ 25–35 increased mRNA levels of these three genes. Overall, ME pretreatment could substantially alleviate PC12 cells injury and downregulate expression of AD-related genes, such as Apaf1, Bace2, and Plcb4. This study has a great nutrigenomics interest and brings new and important light in the field of AD intervention.

Mulberry Fruit Cultivar ‘Chiang Mai’ Prevents Beta-Amyloid Toxicity in PC12 Neuronal Cells and in a Drosophila Model of Alzheimer’s Disease

“…Mitochondria is an organelle function in ATP synthesis and Ca 2+ homeostasis, thus its impairment will provoke [Ca 2+ ] i release and the apoptotic protease-activating factor 1 (Apaf1)-mediated intrinsic apoptotic pathway. Indeed, Aβ 25-35 peptides induced Apaf1-mediated cell death, while pre-treatment with ethanolic extract of Chinese M. nigra for 24 h followed by Aβ [25][26][27][28][29][30][31][32][33][34][35] exposure downregulated Apaf1 [37]. Previous studies showed that cyanidin and kuromanin attenuate Aβ-induced PC12 neurotoxicity by maintaining mitochondrial stability [38].…”

Mori Fructus improves cognitive and neuronal dysfunction induced by beta-amyloid toxicity through the GSK-3β pathway in vitro and in vivo

“…As we previously described, ME showed a total phenolic content of 1.78% (Kim et al, 2010b) and those compounds may exert antioxidant and anti-inflammatory activities that enhance health, particularly in the brain Oh, 2012, 2013). Especially, anthocyanins which are well known to be rich in ME have been shown to modulate the progression of AD (Qin et al, 2013;Shih et al, 2010;Song et al, 2014). For example, one of the major anthocyanin in ME, cyanidin 3-O-glucoside, has improved learning and memory against Aβ toxin via modulation of GSK-3β and tau (Qin et al, 2013).…”

“…A growing body of studies revealed multibioactive functions of mulberry, including anti-inflammatory, antioxidant, anticarcinogenic, and antiapoptotic properties (Kim et al, 2010bKim and Oh, 2013;Liu and Lin, 2012). In addition, it was recently reported that mulberry exerts neuroprotective effects in several models (e.g., Parkinson's disease, AD, cerebral ischemia, vascular dementia, and senescence-accelerated cognitive deficiency) (Kaewkaen et al, 2012;Kang et al, 2006;Kim et al, 2010b;Shih et al, 2010;Song et al, 2014), as well as neuromodulatory effects by inducing nerve growth factor (Kim and Oh, 2013).…”

In vitro and In vivo Studies on Mulberry Extracts: Evaluation of Chemical and Anticancer Activities and Attenuation of Lead Toxicity

“…anti-hyperlipidemia and antiatherogenic properties in a cholesterol-fed-rabbit model [18]as well as neuroprotective effects in PC12 cells in vitro [19] and in mousebrain-injury model [20]. Also, they have anticancer effects of human lung cancer cell line A549 [21], human gastric carcinoma cell lines (SNU-601) [22] and AGS gastric cancer xenograft model cells [23].…”