Jong Keun Son

Britanin suppresses LPS-induced nitric oxide, PGE2 and cytokine production via NF-κB and MAPK inactivation in RAW 264.7 cells.

Little is known about the biological properties of britanin, which is isolated from the flowers of Inula japonica (Inulae Flos). Based on our previous studies that Inulae Flos had anti-inflammation and anti-asthmatic activities, we tried to find the bioactive compounds from it. In this study, the anti-inflammatory effects of britanin on the inflammatory mediators as well as on nuclear factor (NF)-кB and mitogen-activated protein (MAP) kinase activation were evaluated in RAW 264.7 cells. Britanin inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) along with the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In addition, britanin reduced the release of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Furthermore, the phosphorylations of MAP kinases (p38 and JNK) in LPS-stimulated RAW 264.7 cells were suppressed by britanin. Moreover, britanin inhibited the NF-κB activation induced by LPS, which was associated with the abrogation of IκBα degradation and subsequent decreases in nuclear p65 levels. This study suggests that the anti-inflammatory activities of britanin might be attributed to the inhibition of iNOS and COX-2 and cytokine expression at least in part, through the attenuation of the phosphorylations of MAP kinases and NF-κB activation via IκBα degradation in macrophages. We conclude that britanin may have potential for the treatment of inflammatory diseases through the down-regulation of MAP kinases and NF-κB mediated activation of macrophages.

Meso-dihydroguaiaretic acid isolated from Saururus chinensis inhibits cyclooxygenase-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells.

Meso-dihydroguaiaretic acid (MDGA) is a medicinal herbal product isolated from the aerial parts of Saururus chinensis that inhibits the cyclooxygenase-2 (COX-2)-dependent phase of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) (IC50 9.8 μM). However, this compound did not inhibit COX-2 protein expression in BMMC at concentrations up to 30 μM, indicating that MDGA directly inhibits COX-2 activity. In addition, this compound consistently inhibited the production of leukotriene C4 (IC50 1.3 μM). These results demonstrate that MDGA inhibits both COX-2 and 5-lipoxygenase. Furthermore, this compound strongly inhibited the degranulation reaction in BMMC (IC50 11.4 μM). Therefore, this compound might provide a basis for novel anti-inflammatory drug development.

DNA topoisomerases I and II inhibitory activity of constituents isolated fromJuglans mandshurica

Nine diarylheptanoids (1–9), one triterpene (10), one sesquiterpenoid (11), one naphthoquinone (12), four tetralones (13–16), one naphthalene carboxylic acid glucoside (17) and six naphthalenyl glycosides (18–23) were isolated from the roots ofJuglans mandshurica Maxi-mowicz (Juglandaceae), and their structures determined from the chemical and spectral data. Here, we report the inhibitory effects, on the DNA topoisomerases I and II activities, of all these compounds. Compounds10 and23 showed more potent inhibitory effects, on the DNA topoisomerases I and II (94.0 and 86.0% inhibitions at the concentration of 5 (μg/mL, respectively), than the positive control compounds, camptothecin and etoposide.

Alleviation of OVA-Induced Airway Inflammation by Flowers of Inula japonica in a Murine Model of Asthma

The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for treating inflammatory diseases. The effects on OVA-induced asthmatic mice of an Inulae Flos extract (IFE) were evaluated in this study. The anti-asthmatic effects of IFE were determined by observing eosinophil recruitment, airway hyper-responsiveness (AHR), Th2 cytokine and IgE levels, and lung histopathology. The IFE treatment effectively reduced the percentage of eosinophils and Th2 cytokines in the bronchoalveolar lavage fluid (BALF) when compared to the levels in OVA-induced mice. IFE also suppressed AHR induced by aerosolized methacholine in OVA-induced mice. The results of the histopathological studies indicate that inflammatory cell infiltration and mucus hypersecretion were both inhibited by the IFE administration when compared to the effect on OVA-induced mice. The IFE treatment also suppressed the serum IgE levels and decreased Th2 cytokines in the supernatant of cultured splenocytes. These results suggest that IFE may have therapeutic potential against asthma.

Two new secoiridoid glycosides from the rhizomes of Gentiana scabra Bunge

Two new secoiridoid glycosides, 4‴-O-β-D-glucopyranosyltrifloroside 1 and 4‴-O-β-D-glucopyranosylscabraside 2, along with three known secoiridoids were isolated from the rhizomes of Gentiana scabra (Gentianaceae) in our recent phytochemical study. Their chemical structures were determined by spectroscopic data including 1D and 2D NMR spectra. The chemotaxonomic significance of the secoiridoid glycosides is briefly discussed.

Flowers of Inula japonica Attenuate Inflammatory Responses

Background The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of inflammatory diseases. In the present study, we investigated the anti-inflammatory properties of Inulae Flos Extract (IFE). Methods The anti-inflammatory effects of IFE against nitric oxide (NO), PGE2, TNF-α, and IL-6 release, as well as NF-κB and MAP kinase activation were evaluated in RAW 264.7 cells. Results IFE inhibited the production of NO and the expression of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW264.7 cells. In addition, IFE reduced the release of pro-inflammatory cytokines, such as TNF-α and IL-6. Furthermore, IFE inhibited the NF-κB activation induced by LPS, which was associated with the abrogation of IκB-α degradation and subsequent decreases in nuclear p65 and p50 levels. Moreover, the phosphorylation of ERK, JNK, and p38 MAP kinases in LPS-stimulated RAW 264.7 cells was suppressed by IFE in a dose-dependent manner. Conclusion These results suggest that the anti-inflammation activities of IFE might be attributed to the inhibition of NO, iNOS and cytokine expression through the down-regulation of NF-κB activation via suppression of IκBα and MAP kinase phosphorylation in macrophages.

Naturally occurring biflavonoid, ochanflavone, inhibits cyclo-oxygenases-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells

Ochnaflavone is a medicinal herbal product isolated from Lonicera japonica that inhibits cyclooxygenase-2 (COX-2) dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC50 values of 0.6μM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the PGD2 product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene C4 (LTC4) in a dose dependent manner, with an IC50 value of 6.56 μM. These results demonstrate that ochnaflavone has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound strongly inhibited degranulation reaction in a dose dependent manner, with an IC50 value of 3.01 μM. Therefore, this compound might provide a basis for novel anti-inflammatory drugs.

Ethanol extracts of Saururus chinensis suppress ovalbumin-sensitization airway inflammation

AIM OF THE STUDYnThe aerial part of Saururus chinensis has been used in folk medicine to treat several inflammatory diseases in China and Korea. Previously, our group reported that anti-asthmatic activity of an ethanol extract of Saururus chinensis (ESC) might occur, in part, via the inhibition of prostaglandin D(2) (PGD(2)) and leukotriene C(4) (LTC(4)) production, and degranulation reaction in vitro, as well as through the down-regulation of interleukin (IL)-4 and eotaxin mRNA expression in an in vivo ovalbumin-sensitization animal model. However, the effects of Saururus chinensis on eicosanoid generation, as well as Th2 cytokines and eotaxin production in an in vivo asthma model, have not been fully investigated. Moreover, it has not been determined whether ESC can ameliorate airway inflammation in vivo. In the present study, we investigated the therapeutic activity of Saururus chinensis on ovalbumin (OVA)-sensitized airway inflammation and its major phytochemical compositions.nnnMATERIALS AND METHODSnAsthma was induced in BALB/c mice by ovalbumin-sensitization and inhalation. ESC (10-100 mg/kg) or dexamethasone (5 mg/kg), a positive control, was administered 7 times orally every 12 h from one day before the first challenge to 1 h before the second challenge. The recruitment of inflammatory cells and hyperplasia of goblet cells were evaluated by H&E and PAS staining. Levels of Th2 cytokines, eotaxin, PGD(2) and LTC(4) were measured to evaluate the anti-inflammatory activity of ESC in OVA-sensitized mice. Contents of major components were analyzed by HPLC using a reversed-phase C18 column.nnnRESULTSnESC (10 mg/kg) suppressed allergic airway inflammation by inhibition of the production of IL-4 (P<0.001), IL-5 (P<0.05), IL-13 (P<0.001), eotaxin (P<0.001), PGE(2) (P<0.001), LTC(4) (P<0.001) in lung extract and IgE level (P<0.001) in the serum. In addition, ESC (50 mg/kg) reduced the infiltration of inflammatory cells and hyperplasia of goblet cells in the lung tissues. The anti-inflammatory effect of ESC was comparable to that of the positive control drug, dexamethasone. Its major phytochemical composition includes manassantin A, B and sauchinone.nnnCONCLUSIONSnThese results suggest that ESC decreased inflammation and mucus secretion in the OVA-induced bronchial asthma model, and its anti-asthmatic activity may occur in part via the inhibition of Th2 cytokines and eotaxin protein expression, as well as through prostaglandin E(2) (PGE(2)) and leukotriene C(4) (LTC(4)) generation. This effects may be attributed particularly to the presence of manassantin A, B and sauchinone major component evidenced by a HPLC analysis.

Manassantin A inhibits cAMP-induced melanin production by down-regulating the gene expressions of MITF and tyrosinase in melanocytes

Abstract:u2002 Microphthalmia‐associated transcription factor (MITF) is inducible in response to cAMP through the cAMP‐responsive element–binding protein (CREB) and plays a pivotal role in the melanocyte‐specific expression of tyrosinase or tyrosinase‐related proteins (TRPs) for melanin biosynthesis. Manassantin A from Saururus chinensis inhibits cAMP‐induced melanin production in B16 melanoma cells. Here, we focused on molecular basis of the antimelanogenic activity. Manassantin A consistently inhibited the cAMP elevator 3‐isobutyl‐1‐methylxanthine (IBMX)‐ or dibutyryl cAMP‐induced melanin production in B16 cells or in melan‐a melanocytes by down‐regulating the expression of tyrosinase or TRP1 gene. Moreover, manassantin A suppressed MITF induction through IBMX‐activated CREB pathway, directly inhibiting the Ser‐133 phosphorylation of CREB. However, manassantin A did not affect IBMX‐increased cAMP levels in these cells but also other cAMP‐dependent melanogenic pathways through post‐translational modifications of MITF. This putative molecular mechanism of manassantin A in the inhibition of melanin production suggests its pharmacological potential in skin hyperpigmentation.

Simultaneous determination of bioactive flavonoids in some selected Korean thistles by high-performance liquid chromatography.

In order to facilitate the quality control of some selected Korean thistles (Cirsii Herb), Cirsium japonicum var ussuriense, C. japonium var spinosissimum, C. setidens, C. pendulum, C. nipponicum, Carduus crispus, and Breea segetum, a simple, accurate and reliable high performance liguid chromatography method was developed for the simultaneous determination of the six flavonoids: luteolin 5-O-glucoside (1), luteolin 7-O-glucoside (2), hispidulin 7-O-neohesperidoside (3), luteolin (4), pectolinarin (5), and apigenin (6), which were selected as the chemical markers of the thistles. Separation was achieved on an Agilent Eclipse XDB-C18 column with a gradient solvent system of 0.1% trifluoroacetic acid aqueous-methanol at a flow-rate of 1.0 mL/min and detected at 254 nm. All six calibration curves showed good linearity (R2 > 0.991). The method was reproducible with intra- and inter-day variations of less than 6%. The recoveries were in the range of 90.01–100.05%. This analysis method was successfully utilized to quantify the six flavonoids in the 22 batches of the thistles. The results demonstrated that this method is simple, reliable and suitable for the quality control of this medicinal herb.