Lingguizhugan decoction protects PC12 cells against Aß25-35-induced oxidative stress and neuroinflammation by modulating NF-κB/MAPK signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is recognized as one of the most prevalent neurodegenerative diseases. Lingguizhugan decoction (LGZGD) is a classical traditional Chinese medicine (TCM). Many studies have shown that LGZGD can alleviate the symptoms of AD. AIM OF THE STUDY: The aim of this study was to assess the neuroprotective effects of LGZGD and elucidate its molecular mechanism on Aß25-35-induced PC12 cells. MATERIALS AND METHODS: PC12 cells were used MTT assays, ELISA, fluorescence probe analyses, Hoechst 33342 staining, immunofluorescent staining and western blot analyses were systematically conducted to evaluate the underlying mechanisms of LGZGD. RESULTS: In Aß25-35-induced PC12 cells, LGZGD remarkably increased cell viability, reduced the generation of TNF-α, IL-1ß, IL-6, MDA and ROS, increased the activity of GSH-Px, inhibited cell apoptosis, downregulated the expression of Bax and cleaved caspase-3, and upregulated the expression of Bcl-2. Moreover, LGZGD modulated the NF-κB/MAPK signaling pathways by upregulating the levels of IκBα and phospho-ERK, while downregulating the levels of phospho-p65, phospho-IκBα, and phospho-p38. Furthermore, LGZGD repressed the nuclear translocation activity of NF-κB p65. Meanwhile, LGZGD increased the expression of phospho-GSK-3ß and reversed the hyperphosphorylation of Tau proteins by inhibiting the activation of the ERK MAPK pathway. CONCLUSIONS: Taken together, the present study suggested that LGZGD may be a valuable drug candidate that can attenuate the neurotoxicity induced by Aß25-35 by modulating the NF-κB/MAPK signaling pathways in PC12 cells.

Quality control of Semen Hoveniae by high-performance liquid chromatography coupled to Fourier transform-ion cyclotron resonance mass spectrometry.

A method based on high-performance liquid chromatography and Fourier transform-ion cyclotron resonance mass spectrometry was developed to control the quality of Semen Hoveniae. First, the chromatographic fingerprint was established in combination with the chemometrics methods such as similarity analysis, cluster analysis, principal component analysis, and orthogonal partial least squares discriminant analysis to discover the qualitative markers. Then, an high-performance liquid chromatography mass spectrometry method was developed to identify the chemical constituents in Semen Hoveniae. Moreover, the content of dihydromyricetin and dihydroquercetin in Semen Hoveniae were determined by high-performance liquid chromatography. As a result, nine common peaks were assigned in the fingerprints and the similarity of the 13 batch samples varied from 0.425 to 0.993, indicating an obviously different quality. Dihydromyricetin and dihydroquercetin were the main qualitative markers to differ the quality of Semen Hoveniae. Meanwhile, a total of 21 chemical compounds were characterized by high-performance liquid chromatography mass spectrometry and six of them were identified by comparing with information of reference standards. Finally, the content of dihydromyricetin and dihydroquercetin in 13 batch samples varied from 0.824  to 7.499 mg/g and from 0.05941  to 4.258 mg/g , respectively. In conclusion, the methods developed here will provide sufficient qualitative and quantitative information for the quality control of Semen Hoveniae.

Grape-seed Polyphenols Play a Protective Role in Elastase-induced Abdominal Aortic Aneurysm in Mice.

Abdominal aortic aneurysm (AAA) is a kind of disease characterized by aortic dilation, whose pathogenesis is linked to inflammation. This study aimed to determine whether grape-seed polyphenols (GSP) has anti-AAA effects and what mechanism is involved, thus to find a way to prevent occurrence and inhibit expansion of small AAA. In our study, AAA was induced by incubating the abdominal aorta of the mice with elastase, and GSP was administrated to the mice by gavage at different doses beginning on the day of the AAA inducement. In in vivo experiments, 800 mg/kg GSP could significantly reduce the incidence of AAA, the dilatation of aorta and elastin degradation in media, and dramatically decrease macrophage infiltration and activation and expression of matrix metalloproteinase (MMP) -2 and MMP-9 in the aorta, compared to the AAA model group. Meanwhile, 400 mg/kg GSP could also but not completely inhibit the occurrence and development of AAA. In in vitro experiments, GSP dose-dependently inhibited mRNA expression of interleukin (IL)-1ß, IL-6 and monocyte chemoattractant protein-1 (MCP-1), and significantly inhibited expression and activity of MMP-2 and MMP-9, thus prevented elastin from degradation. In conclusion, GSP showed great anti-AAA effects and its mechanisms were related to inhibition of inflammation.