Antiviral biflavonoids from Radix Wikstroemiae (Liaogewanggen)

<p>Abstract</p> <p>Background</p> <p><it>Radix Wikstroemiae </it>is a common Chinese herbal medicine. The ethyl acetate fraction of the ethanolic extract of <it>W. indica </it>possesses potent <it>in vitro </it>antiviral activity against respiratory syncytial virus (RSV). This study aims to identify the antiviral components of the active fraction.</p> <p>Methods</p> <p>The active fraction of the <it>Radix Wikstroemiae </it>extract was isolated with chromatographic methods such as silica gel, Sephadex LH-20 and semi-preparative high performance liquid chromatography (HPLC) columns. The structures of the isolated compounds were determined based on spectroscopic analyses. The <it>in vitro </it>antiviral activity of the compounds against RSV was tested with the cytopathic effect (CPE) reduction assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method.</p> <p>Results</p> <p>Four biflavonoids, namely neochamaejasmin B, genkwanol B, genkwanol C and stelleranol, were isolated and characterized. Genkwanol B, genkwanol C and stelleranol, which are stereo isomers of spirobiflavonoids, showed potent anti-RSV activity whereas neochamaejasmin B did not.</p> <p>Conclusion</p> <p>Neochamaejasmin B, genkwanol B, genkwanol C and stelleranol were isolated from <it>Radix Wikstroemiae </it>and the complete absolute configurations of five chiral carbons in stelleranol were substantiated for the first time. Furthermore, the anti-RSV activity of genkwanol B, genkwanol C and stelleranol was reported for the first time.</p

Synthesis, Biological Evaluation of Fluorescent 23-Hydroxybetulinic Acid Probes, and Their Cellular Localization Studies

© 2018 American Chemical Society. 23-Hydroxybetulinic acid (23-HBA) is a complex lupane triterpenoid, which has attracted increasing attention as an anticancer agent. However, its detailed mechanism of anticancer action remains elusive so far. To reveal its anticancer mode of action, a series of fluorescent 23-HBA derivatives conjugated with coumarin dyes were designed, synthesized, and evaluated for their antiproliferative activities. Subcellular localization and uptake profile studies of representative fluorescent 23-HBA probe 26c were performed in B16F10 cells, and the results suggested that probe 26c was rapidly taken up into B10F10 cells in a dose-dependent manner and mitochondrion was the main site of its accumulation. Further mode of action studies implied that the mitochondrial pathway was involved in 23-HBA-mediated apoptosis. Together, our results provided new clues for revealing the molecular mechanism of natural product 23-HBA for its further development into an antitumor agent

Research progress on the role of the Wnt signaling pathway in pituitary adenoma

Pituitary adenoma (PA) is the third most common central nervous system tumor originating from the anterior pituitary, but its pathogenesis remains unclear. The Wnt signaling pathway is a conserved pathway involved in cell proliferation, Self-renewal of stem cells, and cell differentiation. It is related to the occurrence of various tumors, including PA. This article reviews the latest developments in Wnt pathway inhibitors and pathway-targeted drugs. It discusses the possibility of combining Wnt pathway inhibitors with immunotherapy to provide a theoretical basis for the combined treatment of PA

Infection of inbred BALB/c and C57BL/6 and outbred Institute of Cancer Research mice with the emerging H7N9 avian influenza virus

A new avian-origin influenza virus A (H7N9) recently crossed the species barrier and infected humans; therefore, there is an urgent need to establish mammalian animal models for studying the pathogenic mechanism of this strain and the immunological response. In this study, we attempted to develop mouse models of H7N9 infection because mice are traditionally the most convenient models for studying influenza viruses. We showed that the novel A (H7N9) virus isolated from a patient could infect inbred BALB/c and C57BL/6 mice as well as outbred Institute of Cancer Research (ICR) mice. The amount of bodyweight lost showed differences at 7 days post infection (d.p.i.) (BALB/c mice 30%, C57BL/6 and ICR mice approximately 20%), and the lung indexes were increased both at 3 d.p.i. and at 7 d.p.i.. Immunohistochemistry demonstrated the existence of the H7N9 viruses in the lungs of the infected mice, and these findings were verified by quantitative real-time polymerase chain reaction (RT-PCR) and 50% tissue culture infectious dose (TCID50) detection at 3 d.p.i. and 7 d.p.i.. Histopathological changes occurred in the infected lungs, including pulmonary interstitial inflammatory lesions, pulmonary oedema and haemorrhages. Furthermore, because the most clinically severe cases were in elderly patients, we analysed the H7N9 infections in both young and old ICR mice. The old ICR mice showed more severe infections with more bodyweight lost and a higher lung index than the young ICR mice. Compared with the young ICR mice, the old mice showed a delayed clearance of the H7N9 virus and higher inflammation in the lungs. Thus, old ICR mice could partially mimic the more severe illness in elderly patients. </p

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

2β-(Isobutyryloxy)florilenalin, a Sesquiterpene Lactone Isolated from the Medicinal Plant Centipeda minima, Induces Apoptosis in Human Nasopharyngeal Carcinoma CNE Cells

Centipeda minima is a medicinal plant reputed in China as a remedy for nasopharyngeal carcinoma (NPC). In this study, bioactivity-guided fractionation of the anti-NPC compound(s) from C. minima led to the isolation of 2β-(isobutyryloxy)florilenalin (IF), a sesquiterpene lactone. IF showed significant dose- and time- dependent inhibition on the growth of the human nasopharyngeal carcinoma epithelia cells (CNE). It induced apoptosis in CNE cells, as shown by the accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation, caspase-3 activation and PARP cleavage. Such induction was associated with the depletion of mitochondrial membrane potential (ΔΨm) and the release of cytochrome c to cytosol to regulate the expression of Bcl-2 family proteins. These activities led to the cleavage of caspases and the trigger of cell death process. Overall, IF in C. minima showed potent antiproliferative effect of C. minima on NPC cells, suggesting that the plant deserves more extensive investigation for its potential medicinal application

Pulsatilloside C from the roots of Pulsatilla chinensis

A new lupane-type triterpene saponin, pulsatilloside C (1), was isolated from the roots of Pulsatilla chinensis. Its structure was established to be 3 beta,23-dihydroxylup-20(29)-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta- D-glucopyranoside