kuraridin and kurarinone

Protein tyrosine phosphatase 1B is a non-transmembrane protein tyrosine phosphatase and major negative regulator in insulin signaling cascades, and much attention has been paid to protein tyrosine phosphatase 1B inhibitors as potential therapies for diabetes. The screening of a natural compound library led to the discovery of five lavandulyl flavonoids, which were isolated from the roots of Sophora flavescens, as novel PTP1B inhibitors: kuraridin (1), norkurarinone (2), kurarinone (3), 2'-methoxykurarinone (4), and kushenol T (5). The three most potent compounds, 1, 2, and 4 (IC50 < 30 µM), were demonstrated to be noncompetitive inhibitors of protein tyrosine phosphatase 1B based on a kinetic analysis, and they exhibited different inhibitory selectivities against four homologous protein tyrosine phosphatases (T cell protein tyrosine phosphatase, vaccinia H1-related phosphatase, and Src homology domain 2-containing protein tyrosine phosphatases 1 and 2). Compounds 1, 2, and 4 also exhibited cellular activity in the insulin signaling pathway by increasing the insulin-stimulated Akt phosphorylation level in human hepatocellular liver carcinoma HepG2 cells, suggesting their potential for new anti-insulin-resistant drug developments.

Topics: Chalcones; Flavonoids; Hep G2 Cells; Humans; Inhibitory Concentration 50; Insulin; Kinetics; Monoterpenes; Plant Extracts; Plant Roots; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases; Signal Transduction; Small Molecule Libraries; Sophora

Airborne biological particles containing viruses, bacteria, and/or fungi can be toxic and cause infections and allergy symptoms. Recently, natural materials such as tea tree oil and Sophora flavescens have shown promising antimicrobial activity when applied as air filter media. Although many of these studies demonstrated excellent antimicrobial efficacy, only a few of them considered external environmental effects such as the surrounding humidity, temperature, and natural degradation of chemicals, all of which can affect the antimicrobial performance of these natural materials. In this study, we investigated the antimicrobial durability of air filters containing airborne nanoparticles from S. flavescens for 5 months. Antimicrobial tests and quantitative chemical analyses were performed every 30 days. Morphological changes in the nanoparticles were also evaluated by scanning electron microscopy. The major antimicrobial compounds remained stable and active for ~90 days at room temperature. After about 90 days, the quantities of major antimicrobial compounds decreased noticeably with a consequent decrease in antimicrobial activity. These results are promising for the implementation of new technologies using natural antimicrobial products and provide useful information regarding the average life expectancy of antimicrobial filters using nanoparticles of S. flavescens.

Topics: Air Filters; Anti-Infective Agents; Chalcones; Equipment Design; Escherichia coli; Flavanones; Flavonoids; Microscopy, Electron, Scanning; Monoterpenes; Nanoparticles; Plant Extracts; Sophora; Staphylococcus epidermidis; Temperature

The study was designed as one of a series to find novel anticancer compounds from Chinese herbs. For this purpose, we screened an ethanol extract of 300 herbs against SGC-7901 cells. Sophora flavescen was included in those showing potential cytotoxic activity. Target compounds were therefore isolated and analyzed on analytical HPLC. Chromatography showed only one peak with a purity of 97%. The ESI-MS spectrum showed two molecular ions: m/z 424(M+) and 438(M+). Furthermore, combining the data of 1HNMR and 13CNMR, it was deduced that this product was a mixture of two compounds; kuraridin (1) and nor-kurarinone (2). The concentration was [1]:[2]=9:10, the chemical structural formulae are C25H28O6 and C26H30O6. In this study, mechanisms involved by the mixture of compounds 1 and 2-induced growth inhibition including apoptosis and G2/M phase arrest in human gastric adenocarcinoma SGC-7901 cells were examined for the first time. Triggering of the mitochondrial apoptotic pathway was demonstrated by loss of mitochondrial membrane potential, reduction in the Bcl-2/Bax ratio, and significant activation and cleavage of caspase-3. Additionally, the production of reactive oxygen species (ROS) was also increased. Taken together, our results indicated that the cytotoxic efficacy of the mixture of compounds 1 and 2 is mainly due to induction of cell cycle arrest and apoptosis.

Topics: Adenocarcinoma; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Chalcones; Flavonoids; G2 Phase Cell Cycle Checkpoints; Humans; Medicine, Chinese Traditional; Membrane Potential, Mitochondrial; Mitochondria; Monoterpenes; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Sophora; Stomach Neoplasms

Oxidized low-density lipoprotein (oxLDL) and reactive oxygen species (ROS) play key roles in the early stage of atherosclerosis. Nitric oxide (NO) and ROS are responsible for regulation of the transcriptional pathways of nuclear Factor-kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK), key regulators of cellular inflammatory and immune responses. Previously, we examined LDL-antioxidant activities of the nine flavonoids isolated from Sophora flavescens. Among these, two lavandulyl flavonoids, kurarinone (1) and kuraridin (2) inhibited inducible nitric oxide synthase (iNOS)-dependent NO production and ROS generation, and suppressed remarkably the expression of inflammatory cytokines, CCL2, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and iNOS in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Moreover, compounds 1 and 2 attenuated NF-kappaB activation by inhibition of IkappaBalpha proteolysis and p65 nuclear translocation, as well as phosphorylation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK), and p38 MAP kinases.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cell Line; Chalcones; Flavonoids; Inflammation Mediators; Lipopolysaccharides; Mice; Mitogen-Activated Protein Kinases; Monoterpenes; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Plant Extracts; Reactive Oxygen Species; Sophora