Zhenzuo Wang

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

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.

Involvement of the ERK pathway in the protective effects of glycyrrhizic acid against the MPP+-induced apoptosis of dopaminergic neuronal cells

Glycyrrhizic acid (GA), a major compound separated from Radix Glycyrrhizae, has been shwon to exert various biochemical effects, including neuroprotective effects. In the present study, we investigated the protective effects of GA against 1-methyl-4-phenylpyridinium (MPP+)-induced damage to differentiated PC12 (DPC12) cells. Compared with the MPP+-treated cells, GA markedly improved cell viability, restored mitochondrial dysfunction, suppressed the overexpression of cleaved poly(ADP-ribose) polymerase (PARP), and suppressed the overproduction of lactate dehydrogenase (LDH) and intracellular Ca2+ overload. The protective effects of GA on cell survival were further confirmed in primary cortical neurons. GA markedly increased the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), as well as its migration from the cytoplasm to nucleus. PD98059, an inhibitor of ERK, blocked GA-enhanced ERK activation and reduced cell viability. However, pre-treatment with GA had no effects on the expression of phosphorylated AKT (p-AKT) and total AKT (t-AKT). These results indicate that the GA-mediated neuroprotective effects are associated with its modulation of multiple anti-apoptotic and pro-apoptotic factors, particularly the ERK signaling pathway. This study provides evidence supporting the use of GA as a potential therapeutic agent for the treatment of neurodegenerative diseases and neuronal injury.

Liquiritigenin Induces Tumor Cell Death through Mitogen-Activated Protein Kinase- (MPAKs-) Mediated Pathway in Hepatocellular Carcinoma Cells

Liquiritigenin (LQ), separated from Glycyrrhiza radix, possesses anti-inflammatory, antihyperlipidemic, and antiallergic effects. Our present study aims to investigate the antihepatocellular carcinoma effects of LQ both in cell and animal models. LQ strikingly reduced cell viability, enhanced apoptotic rate, induced lactate dehydrogenase over-release, and increased intracellular reactive oxygen species (ROS) level and caspase 3 activity in both PLC/PRL/5 and HepG2 cells. The expression of cleaved PARP, the hall-marker of apoptosis, was enhanced by LQ. LQ treatment resulted in a reduction of the expressions of B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL), and an increase of the phosphorylation of c-Jun N-terminal kinases (JNK) and P38. LQ-mediated cell viability reduction, mitochondrial dysfunction, apoptosis related protein abnormal expressions, and JNK and P38 activation were partially abolished by N-Acetyl-L-cysteine (a ROS inhibitor) pretreatment. Moreover, LQ suppressed the activation of extracellular signaling-regulated kinase (ERKs) and reduced the translocation of phosphor-ERKs from cytoplasm to nucleus. This antitumor activity was further confirmed in PLC/PRL/5-xenografted mice model. All these data indicate that the antihepatocellular carcinoma effects of LQ are related to its modulation of the activations of mitogen-activated protein kinase (MAPKs). The study provides experimental evidence supporting LQ as a potential therapeutic agent for hepatocellular carcinoma treatment.

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

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.

Synthesis of nanocrystalline materials of composite oxides based on BaTiO3 by using stearic acid-sol method

Abstract Nanocrystalline materials of BaTiO 3 and Ba 1−x Pb x TiO 3 ( x = 0.1−1.0) with a single phase and the perovskite structure have been prepared by stearic acid-sol method; the average grain diameters of some materials were less than 15 nm. The morphology and properties of the materials were characterized by X-ray powder diffractometer, differential thermal analyzer and transmission electron microscope.

39 Studies on the antidiabetic activity of apigenin in mice with streptozotocin-induced diabetes

Objectives A complex endocrine and metabolic disorder, diabetes mellitus affects about 6% of the population worldwide and is rapidly reaching epidemic proportions. The present study aimed to evaluate the antidiabetic effects of apigenin in mice with streptozotocin (STZ)-induced diabetes. Methods Diabetes in mice was induced by intraperitoneal injection of a single dose of STZ (200 mg/kg body weight) dissolved in 0.1 mol/L citrate buffer at pH 4.5. Non-diabetic mice serving as a control group only received citrate buffer. Diabetic mice were randomly divided into three groups (n = 10): a diabetic group, a metformin hydrochloride group (120 mg/kg) and an apigenin-treated group (100 mg/kg). Results Apigenin treatment for 4 weeks strongly reversed the abnormal reduction in body weight (p < 0.01) and decreased blood glucose by nearly 22.7% compared with diabetic mice (p < 0.001). The oral glucose tolerance test (OGTT) was used to avoid false positive results obtained from fasting blood glucose levels. Compared with the non-treated diabetic mice, apigenin treatment significantly prevented blood glucose levels from increasing, especially at 30, 60 and 120 min (p<0.05). Moreover, apigenin treatment strongly increased serum insulin and pyruvate kinase sensitivity. Furthermore, superoxide dismutase and glutathione peroxidase were significantly enhanced and malondialdehyde was decreased by apigenin, indicating the antioxidant effect of apigenin. Conclusions The results show that apigenin possesses antioxidant and antidiabetic properties, further supporting the use of apigenin in folk medicine for diabetic mellitus.