Molecular network-based analysis of guizhi-shaoyao-zhimu decoction, a TCM herbal formula, for treatment of diabetic peripheral neuropathy.

AIM: Guizhi-shaoyao-zhimu decoction (GSZ), a traditional Chinese medicine (TCM) herbal formula, has been shown effective in the treatment of diabetic peripheral neuropathy (DPN). In this study, network analysis was performed to decipher the molecular mechanisms of GSZ in the treatment of DPN. METHODS: The chemical components of the 3 herbs forming GSZ, ie, Ramulus Cinnamomi (Guizhi), Paeonia lactiflora (Shaoyao) and Rhizoma Anemarrhenae (Zhimu), were searched in Chinese medicine dictionaries, and their target proteins were identified in PubChem. DPN genes were searched in PubMed gene databases. Ingenuity Pathway Analysis (IPA) was used to build the GSZ pharmacological network and DPN molecular network. The canonical pathways between the two networks were compared to decipher the molecular mechanisms of GSZ in the treatment of DPN. RESULTS: Sixty-one protein targets for Guizhi, 31 targets for Shaoyao, 47 targets for Zhimu, as well as 23 genes related to DPN were identified and uploaded to IPA. The primary functions of the DPN molecular network were inflammatory response, metabolic disease, cellular assembly and organization. As far as the pharmacological network functions were concerned, Guizhi target proteins were involved in neurological disease, inflammatory disease, cellular growth and proliferation, cell signaling, molecular transport, and nucleic acid metabolism, Shaoyao target proteins were related to neurological disease, inflammatory disease, and Zhimu target proteins focused on cell death and survival, cellular movement, immune cell trafficking, DNA replication, recombination and repair, and cell cycle. In the three-herb combination GSZ, several new network functions were revealed, including the inflammatory response, gene expression, connective tissue development and function, endocrine system disorders, and metabolic disease. The canonical pathway comparison showed that Shaoyao focused on IL-12 signaling and production in macrophages, and Zhimu focused on TNFR2 signaling, death receptor signaling, ILK signaling, IL-17A in gastric cells, IL-6 signaling, IL-8 signaling, the role of JAK1, JAK2, and TYK2 in interferon signaling, IL-9 signaling, HMGB1 signaling, NO production and ROS production in macrophages, whereas GSZ focused aryl hydrocarbon receptor signaling and apoptosis signaling in addition to those pathways induced by Guizhi, Shaoyao and Zhimu. CONCLUSION: Although each single herb can affect some DPN-related functions and pathways, GSZ exerts more effects on DPN-related functions and pathways. The effects of GSZ on aryl hydrocarbon receptor signaling and apoptosis signaling pathways may be the key components of its total molecular mechanisms.

Effect of curcumin on aged Drosophila melanogaster: a pathway prediction analysis.

OBJECTIVE: To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. METHODS: Microarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpring GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection (MCODE) were used to establish the protein-protein interaction (PPI) network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for pathway analysis. RESULTS: A total of 87 genes expressed differentially in D. melanogaster melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway. CONCLUSION: Genes and their associated pathways in D. melanogaster melanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curcumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.

Ginsenoside Rg1 reduces toxicity of fine particulate matter on human alveolar epithelial cells: a preliminary observation.

Fine particulate matter (PM2.5) is a significant environmental pollutant responsible for a number of human diseases. Ginsenoside Rg1 (Rg1) is likely to have the potential to relieve PM2.5­induced cell injury. The present study is designed to preliminarily observe the harmful effect of PM2.5 and the protective effect of Rg1 against PM2.5 on human A549 lung epithelial cells in vitro. The cytotoxic effects of the PM2.5 or Rg1 on A549 cells were measured by means of cell viability, and then exposure concentration of PM2.5 and pretreatment concentration of Rg1 used in the following assays were established. The A549 cells were pretreated with Rg1 for 1 h and then exposed to PM2.5 for 24 h. The levels of lactate dehydrogenase (LDH) in the cell culture supernatant and malondialdehyde (MDA) within the cells were assayed. The present results revealed that 200­1,200 µg/ml of PM2.5 decreased the viability of A549 cells significantly in a concentration­dependent manner; however, 50­400 µg/ml of Rg1 had no significant effect. Pretreatment with 100, 200 or 400 µg/ml Rg1 significantly diminished the 200 µg/ml PM2.5­induced A549 cell viability and decreased LDH leakage and MDA generation in a concentration­dependent manner. These results indicated that PM2.5 induced cell injury and Rg1, antagonized PM2.5­induced cell injury to a certain extent.