title: Liquiritin modulates ERK‑ and AKT/GSK‑3β‑dependent pathways to protect against glutamate‑induced cell damage in differentiated PC12 cells.
abstract: 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.
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Lesheng
authors.initials: L
authors.lastname: Teng
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Qingfan
authors.initials: Q
authors.lastname: Meng
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Lu
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Zhenzuo
authors.initials: Z
authors.lastname: Wang
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000378:metabolism; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D045304:Cytochromes c; D048049:Extracellular Signal-Regulated MAP Kinases; D044950:Flavanones; D005419:Flavonoids; D005960:Glucosides; D018698:Glutamic Acid; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020011:Protective Agents; D051057:Proto-Oncogene Proteins c-akt; D051028:bcl-2-Associated X Protein; C000605508:Gsk3b protein, rat; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C512196:liquiritin