lignans and phillyrin

In obese adipose tissue, tumor necrosis factor-α secreted from macrophages plays an important role in the adipocyte dysfunctions, including insulin resistance, lipolytic acceleration, and changes of adipokines, which promote the development of obesity-related complications. Phillyrin, an active ingredient found in many medicinal plants and certain functional foods, elicits anti-obesity and anti-inflammatory properties in vivo. The aim of the current study was to investigate the role of phillyrin in preventing tumor necrosis factor α-induced insulin resistance or lipolytic acceleration in 3T3-L1 adipocytes. Our results showed that phillyrin partially restored insulin-stimulated 2-DOG uptake, which was reduced by tumor necrosis factor-α, with concomitant restoration in serine phosphorylation of insulin receptor substrate-1 and insulin-stimulated Glut4 translocation to plasma membrane. Phillyrin also dose-dependently prevented tumor necrosis factor α-stimulated adipocyte lipolysis with preserved downregulation of perilipin. The mitogen-activated protein kinases and I kappaB kinase activation was promoted in tumor necrosis factor α-stimulated adipocytes, but pretreatment with 40 µM phillyrin inhibited the phosphorylation of extracellular signal-regulated kinases1/2, stress-activated protein kinase/Jun N-terminal kinase and I kappaB kinase (p<0.05). Moreover, phillyrin could inhibit the expressions of interleukin-6 and monocyte chemoattractant protein-1 induced by tumor necrosis factor-α. Using transwell coculture method with 3T3-L1 adipocytes and RAW 264.7 macrophages, the enhanced productions of tumor necrosis factor-α and free fatty acids in the medium were significantly reduced by phillyrin (p<0.05). These results indicate that phillyrin exerts a beneficial effect on adipocyte dysfunctions induced by tumor necrosis factor-α through suppression of the activation of I kappaB kinase and N-terminal kinase. Phillyrin may have the potential to ameliorate the inflammatory changes and insulin resistance in obese adipose tissue.

Topics: 3T3-L1 Cells; Animals; Anti-Inflammatory Agents; Cell Survival; Glucose; Glucosides; I-kappa B Kinase; Insulin Resistance; Lignans; Lipolysis; Mice; Obesity; Tumor Necrosis Factor-alpha

A simple and reproducible HPLC-photodiode array detector method has been described for evaluating and controlling quality of Forsythia suspensa extract (FSE). First, by analysis of chromatographic fingerprints, the similarities of chromatograms of FSE samples from the same pharmaceutical company exceeded 0.999, 0.997 and 0.960, respectively, although they were much lower from different pharmaceutical companies. Second, by further comparing many batches of extract chromatograph charts with the corresponding reference herb materials, the "common peaks" 3, 5, 7 and 10 were defined as "marker peaks", which were identified as (+)-pinoresinol-beta-D-glucoside, forsythiaside, phillyrin and phillygenin, respectively. Third, four "marker peaks" were simultaneously determined based on fingerprint chromatogram for further controlling the quality of FSE quantitatively. Namely, the newly developed method was successfully applied to analyze 38 batches of FSE samples supplied by three pharmaceutical factories, which showed acceptable linearity, intra-day precision (RSD<2.76%), inter-day precision (RSD<3.43%) and the average recovery rates in the range of (95.38+/-2.96)% to (101.60+/-3.08)%. At last, hierarchical clustering analysis and Bayes discriminant analysis statistical methods were used to classify and differentiate the 38 FSE samples to provide the basis for guiding reasonable use of FSE and controlling its quality better.

Topics: Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Forsythia; Glucosides; Glycosides; Lignans; Magnetic Resonance Spectroscopy; Plant Extracts; Plants, Medicinal; Quality Control

Bioactivity-guided fractionation of the methanol extract of the fruits of Forsythia suspensa Vahl has led to the isolation of two new monoepoxylignans, forsythialan A (1) and B (2), together with a known tetrahydrofurofuran lignan, phillyrin (3). The structures of compounds 1 and 2 were elucidated by spectroscopic methods. The antioxidant activities of these lignans have been assessed by evaluating their protective effects against peroxynitrite-induced oxidative stress. The compounds 1 and 2 showed protective effects against renal epithelial cell injury by 3-morpholinosydnonimine (SIN-1), a peroxynitrite generator. The relatively stronger antioxidant activities of compounds 1 and 2 may be associated with the presence of aromatic hydroxy function.

Topics: Animals; Antioxidants; Chromatography, High Pressure Liquid; Forsythia; Fruit; Furans; Glucosides; Lignans; LLC-PK1 Cells; Magnetic Resonance Spectroscopy; Molecular Structure; Molsidomine; Nitric Oxide Donors; Oxidative Stress; Peroxynitrous Acid; Plant Extracts; Swine