Hexane extract from Polygonum multiflorum attenuates glutamate-induced apoptosis in primary cultured cortical neurons

Guo

et al. 2014

Braz J Med Biol Res

The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.

“…ERK and AKT activations are major factors related to cell survival (14,15). Activated ERKs and stress-activated c-Jun N-terminal kinase-P38 have important roles in PC12 survival (27).…”

Section: Discussionmentioning

confidence: 99%

“…Several signaling pathways are involved in the regulation of glutamate-induced neurotoxicity (14,15). Alteration of mitochondrial function is one of the factors Correspondence: L.S.…”

Section: Introductionmentioning

confidence: 99%

ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells

Guo

et al. 2014

Braz J Med Biol Res

Molecular Medicine Reports

“…Glutamate-mediated excitotoxicity occurs as part of the ischemic cascade (10) and is associated with numerous diseases, including amyotrophic lateral sclerosis, autism, Alzheimer’s disease and certain forms of mental retardation (9). Several signaling pathways are involved in the regulation of glutamate-induced neurotoxicity (11,12). Extracellular signal-regulated kinases (ERKs) and AKT signaling pathways have been proposed to contribute to cell differentiation, proliferation, survival and apoptosis (13–15).…”

Section: Introductionmentioning

confidence: 99%

Liquiritin modulates ERK- and AKT/GSK-3β-dependent pathways to protect against glutamate-induced cell damage in differentiated PC12 cells

Teng

Meng

Lü

et al. 2014

Glutamate has a key role in the neuronal cell damage associated with Alzheimer’s and Parkinson’s diseases. Liquiritin (LQ), a major constituent of Glycyrrhiza Radix, possesses various pharmacological activities. The present study investigated the neuroprotective effect of LQ against glutamate-induced cell damage in the differentiated PC12 (DPC12) rat pheochromocytoma cell line. Pretreatment with 25 and 50 μM LQ for 3 h resulted in a significant increase in cell viability and inhibited excessive lactate dehydrogenase release in glutamate-exposed DPC12 cells. LQ also ameliorated glutamate-induced nuclear and mitochondrial apoptotic alterations, intracellular calcium overload and the abnormal expression of apoptosis-related proteins, including cytochrome c, B-cell lymphoma (Bcl)-2 and Bcl2-associated X protein. Treatment with LQ alone or in combination with glutamate was found to enhance the phosphoactivation of extracellular signal-regulated kinases (ERKs), AKT and its downstream element glycogen synthase kinase-3β (GSK3β), in a time-dependent manner. However, no effect was observed on the expression of total-ERKs, -AKT and -GSK3β. Furthermore, pre-incubation with 10 μM PD98059 or LY94002, inhibitors of ERK and phosphatidylinositide 3-kinase, respectively, for 30 min significantly suppressed the LQ-induced increase in glutamate-exposed DPC12 cell viability. To the best of our knowledge, the present study provides the first experimental evidence that LQ has a neuroprotective effect against glutamate toxicity in DPC12 cells, predominantly through the ERK and AKT/GSK-3β pathways. Therefore, LQ may have potential for the treatment of neurodegenerative diseases.

“…Research showed that F. multiflora has potent antioxidative and cytoprotective properties [1], enhanced purgative effects, promoted diuresis and choleretic effects [2], and exerted a neuroprotective effect against glutamate-induced neurotoxicity [3]. 2,3,5,4'-tetrahydroxy stilbene-2-O-ß-Dglucoside (THSG) is an active component in F. multiflora, which possesses anti-hyperlipidemic [4], anti-oxidative, anti-inflammatory, endothelial-protective activities [5].…”

Section: Introductionmentioning

confidence: 99%

“…The pharmacological research revealed that THSG has a potential impact on human health. As a stilbene, THSG and resveratrol (3,5,4'-trihydroxy-trans-stilbene) belong to phenylpropanoids characterized by a 1,2-diphenylethylene backbone. Plant stilbenes are derived from phenylalanine biosynthesis via the general phenylpropanoid pathway.…”

Section: Introductionmentioning

confidence: 99%

Isolation of biosynthesis related transcripts of 2,3,5,4'-tetrahydroxy stilbene-2-O-β-D-glucoside from Fallopia multiflora by suppression subtractive hybridization

et al. 2014

2,3,5,4'-tetrahydroxy stilbene-2-O-ß-D-glucoside (THSG) exerts multiple pharmacodynamic actions, found in Fallopia multiflora, but the biosynthesis pathway of THSG is still unclear. To clear this ambiguity, we constructed suppression subtractive hybridization (SSH) libraries to screen the genes involved in THSG biosynthesis from two F. multiflora varieties, which vary significantly in THSG content. Twelve non-redundant differentially expressed sequence tags were obtained and the full lengths of 4 unreported fragments were amplified by rapid amplification of cDNA ends. We totally got 7 fulllength transcripts, and all of them were aligned to the transcriptome and digital gene expression tag profiling database of four F. multiflora tissues (root, stem and leaf from Deqing F. multiflora and another root from Chongqing F. multiflora; data unpublished) using local BLAST. The results showed that there was a significant, organ specific difference in the expression of fragments and full-length sequences. All the sequences were annotated by aligning to nucleotide and protein databases. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that THSG biosynthesis was correlated with multiple life activities.