Immune-enhancing screening of fourteen plants on murine macrophage RAW 264.7 cells

Purpose: To investigate the potential immune-enhancing effects of fourteen natural plant extracts on mouse macrophage RAW 264.7 cells.Methods: Fourteen plant extracts from 7 different plants were tested on RAW 264.7 cells to determine their immunostimulant activities. Methylthiazolydiphenyltetrazolium bromide (MTT) and Griess assays were performed to evaluate cell viability and nitric oxide (NO) production, respectively. Then, immune related proteins were measured by western blot analysis, while cytokines and phagocytic activity were determined by enzyme-linked immunosorbent assay (ELISA) method.Results: Among the 14 plant extracts, the hot water extract of Agastache rugose was selected based on the screening results on NO production. The hot water extract of A. rugose significantly increased NO production in a concentration-dependent manner without any cytotoxicity. In addition, the expression levels of proteins (iNOS and COX-2) and cytokines (TNF-α, IL-1β, IL-6 and IL-12) closely related to immune reaction were also significantly upregulated. Furthermore, phagocytic activity of RAW 264.7 cells significantly increased following treatment with A. rugosa.Conclusion: The hot water extract of A. rugosa exhibits significant immune-stimulant activity. Therefore, A. rugosa can be used as a natural resource for immune enhancement or dietary supplement.Keywords: Immune enhancing activity, Macrophage polarization, Natural plant extracts, Agastache rugosa, RAW 264.

Anti-influenza virus activity of extracts from the stems of Jatropha multifida Linn. collected in Myanmar

Background: To contribute to the development of novel anti-influenza drugs, we investigated the anti-influenza activity of crude extracts from 118 medicinal plants collected in Myanmar. We discovered that extract from the stems of Jatropha multifida Linn. showed anti-influenza activity. J. multifida has been used in traditional medicine for the treatment of various diseases, and the stem has been reported to possess antimicrobial, antimalarial, and antitumor activities. However, the anti-influenza activity of this extract has not yet been investigated. Methods: We prepared water (H2O), ethyl acetate (EtOAc), n-hexane (Hex), and chloroform (CHCl3) extracts from the stems of J. multifida collected in Myanmar, and examined the survival of Madin-Darby canine kidney (MDCK) cells infected with the influenza A (H1N1) virus, and the inhibitory effects of these crude extracts on influenza A viral infection and growth in MDCK cells. Results: The H2O extracts from the stems of J. multifida promoted the survival of MDCK cells infected with the influenza A H1N1 virus. The EtOAc and CHCl3 extracts resulted in similar, but weaker, effects. The H2O, EtOAc, and CHCl3 extracts from the stems of J. multifida inhibited influenza A virus H1N1 infection; the H2O extract possessed the strongest inhibitory effect on influenza infection in MDCK cells. The EtOAc, Hex, and CHCl3 extracts all inhibited the growth of influenza A H1N1 virus, and the CHCl3 extract demonstrated the strongest activity in MDCK cells. Conclusion: The H2O or CHCl3 extracts from the stems of J. multifida collected in Myanmar demonstrated the strongest inhibition of influenza A H1N1 viral infection or growth in MDCK cells, respectively. These results indicated that the stems of J. multifida could be regarded as an anti-influenza herbal medicine as well as a potential crude drug source for the development of anti-influenza compounds

ミャンマー産植物Premna serratifoliaとJatropha multifida及び海綿Clathria proliferaに含まれるメラニン産生制御成分に関する研究

富山大学・富医薬博甲第305号・禹 昭年・2019/03/26当該博士論文は以下の項評論文で構成されています。①Woo, SY., Win, N.N., Wong, C.P. et al. Two new pyrrolo-2-aminoimidazoles from a Myanmarese marine sponge, Clathria prolifera, J Nat Med (2018) 72: 803-807. https://doi.org/10.1007/s11418-018-1205-y This is a pre-print of an article published in Journal of Natural Medicines. The final authenticated version is available online at: https://doi.org/10.1007/s11418-018-1205-y”.②So-Yeun Woo et al. Lignans with melanogenesis effects from Premna serratifolia wood, Fitoterapia (2019) 133:35-42. https://doi.org/10.1016/j.fitote.2018.12.008③So-Yeun Woo et al. A New Tetrahydrofuran Lignan from Premna serratifolia Wood, Natural Product Communications (2019) 14:113-116. https://doi.org/10.1177/1934578X1901400130富山大

Antioxidative Effects of Chrysoeriol via Activation of the Nrf2 Signaling Pathway and Modulation of Mitochondrial Function

Retinal pigment epithelium (RPE) cell dysfunction caused by excessive oxidative damage is partly involved in age-related macular degeneration, which is among the leading causes of visual impairment in elderly people. Here, we investigated the protective role of chrysoeriol against hydrogen peroxide (H2O2)-induced oxidative stress in RPE cells. The cellular viability, reactive oxygen species (ROS) generation, and mitochondrial function of retinal ARPE-19 cells were monitored under oxidative stress or pre-treatment with chrysoeriol. The expression levels of mitochondrial-related genes and associated transcription factors were assessed using reverse transcription–quantitative polymerase chain reaction (RT-qPCR). Moreover, the protein expression of antioxidant signal molecules was characterized by Western blot analysis. Chrysoeriol significantly increased cell viability, reduced ROS generation, and increased the occurrence of antioxidant molecules in H2O2-treated ARPE-19 cells. Additionally, mitochondrial dysfunction caused by H2O2-induced oxidative stress was also considerably diminished by chrysoeriol treatment, which reduced the mitochondrial membrane potential (MMP) and upregulated mitochondrial-associated genes and proteins. Chrysoeriol also markedly enhanced key transcription factors (Nrf2) and antioxidant-associated genes (particularly HO-1 and NQO-1). Therefore, our study confirms the protective effect of chrysoeriol against H2O2-induced oxidative stress in RPE cells, thus confirming that it may prevent mitochondrial dysfunction by upregulating antioxidant-related molecules

Novel aminopyridazine derivative of minaprine modified by radiolysis presents potent anti-inflammatory effects in LPS-stimulated RAW 264.7 and DH82 macrophage cells

Abstract Radiation molecularly transforms naturally occurring products by inducing the methoxylation, hydroxylation, and alkylation of parent compounds, thereby affecting the anti-inflammatory capacities of those compounds. Minaprine (1) modified by ionizing radiation generated the novel hydroxymethylation hydropyridazine (2), and its chemical structure was determined based on NMR and HRESIMS spectra. Compared to the original minaprine, the novel generated product showed a highly enhanced anti-inflammatory capacity inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 and DH82 macrophage cells. In addition, minaprinol (2) effectively inhibited cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) at the protein level and pro-inflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10) production in macrophages

In-operando spectroscopic ellipsometry studies of IrO2 dynamic instabilities: Guide to in-situ growth of pyrochlore iridate thin films

The instability of iridium oxide at high temperature has long been a bottleneck for in growing pyrochlore iridate thin films in a vacuum chamber. To overcome this problem, we investigated the chemical instability of IrO2 thin films, which are the simplest form of iridate, via in-operando spectroscopic ellipsometry (SE). We observed that IrO2 thin films undergo IrO2 dissociation and IrO3 gas formation depending on the thermodynamic conditions. The chemical kinetics observations of IrO2 were confirmed by ex-situ X-ray diffraction and atomic force microscopy. SE experimental data were compared with models used to describe the evolution of the two chemical reactions. Real-time in-operando SE analysis based on the Maxwell Garnett theory yielded a precise IrO2 dissociation speed for the given thermodynamic conditions. Moreover, the real-time in-operando SE technique allowed us to observe the phase transition from solid IrO2 to gaseous IrO3. This study on the chemical instability of IrO2 at high temperature affords insights into a new method for in-situ pyrochlore iridate and other iridates thin-film growth. © 2019 Korean Physical Society. Published by Elsevier B.V. All rights reserved

Lutonarin from Barley Seedlings Inhibits the Lipopolysacchride-Stimulated Inflammatory Response of RAW 264.7 Macrophages by Suppressing Nuclear Factor-κB Signaling

Extracts from barley seedlings (BS) have known antioxidant and anti-inflammatory activities. The flavonoid lutonarin (LN) is a component of BS extract and has several known bioactivities. Here, we evaluated LN anti-inflammatory efficacy against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Lutonarin was isolated from BS by methanol extraction and characterized by ultra-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Lutonarin did not reduce the viability or enhance the apoptosis rate of RAW 264.7 macrophages at concentrations up to 150 µM. Concentrations within 20–60 µM dose-dependently suppressed the LPS-induced expression, phosphorylation, and nuclear translocation of the inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Furthermore, LN suppressed the LPS-induced upregulation of proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α and of the inflammatory enzyme cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Lutonarin may be a safe and effective therapeutic agent for alleviation of pathological inflammation

Spin-orbit coupling induced band structure change and orbital character of epitaxial IrO2 films

We investigated the electronic structure of IrO2 to address the controversy regarding spin-orbit coupling (SOC) effects in metallic 5d transition-metal oxides. Two issues have come to the forefront: (1) SOC effects on electronic structure and physical properties of IrO2 and (2) the possible formation of a novel ground state in this material, the J(eff) = 1/2 state. To better understand the SOC mechanism, we grew epitaxial IrO2 films whose dc resistivity values were comparable with those of a single crystal. We obtained polarization-dependent optical and x-ray absorption spectra (XAS) and compared these results with those acquired using the generalized gradient approximation (GGA) and GGA + SOC calculations. From the optical spectra, peak structures were identified at 0.4 and 2.0 eV, which could only be explained using the GGA + SOC calculation. This suggests that SOC plays an important role in the electronic structure of IrO2. From the polarization-dependent O 1s XAS spectra, we observed that the empty state near the Fermi level lacks involvement of an Ir d(xy) orbital. Despite the importance of SOC in IrO2, the J(eff) = 1/2 state does not form in metallic IrO2

Comparative Analysis of Policosanols Related to Growth Times from the Seedlings of Various Korean Oat (Avena sativa L.) Cultivars and Screening for Adenosine 5′-Monophosphate-Activated Protein Kinase (AMPK) Activation

The objectives of this research were to evaluate the policosanol profiles and adenosine-5′-monophosphate-activated protein kinase (AMPK) properties in the seedlings of Korean oat (Avena sativa L.) cultivars at different growth times. Nine policosanols in the silylated hexane extracts were detected using GC-MS and their contents showed considerable differences; specifically, hexacosanol (6) exhibited the highest composition, constituting 88–91% of the total average content. Moreover, the average hexacosanol (6) contents showed remarkable variations of 337.8 (5 days) → 416.8 (7 days) → 458.9 (9 days) → 490.0 (11 days) → 479.2 (13 days) → 427.0 mg/100 g (15 days). The seedlings collected at 11 days showed the highest average policosanol content (541.7 mg/100 g), with the lowest content being 383.4 mg/100 g after 5 days. Interestingly, policosanols from oat seedlings grown for 11 days induced the most prevalent phenotype of AMPK activation in HepG2 cells, indicating that policosanols are an excellent AMPK activator