Natural Products Targeting Wnt/β-catenin Signaling Pathway

The canonical Wnt/β-catenin signaling pathways play an important role in the embryonic development, cell proliferation, differentiation, and adhesion. Therefore, the abnormal activation and repression have been associated with uncontrolled homeostasis in human tissues. In particular, the activation of Wnt signaling is highly correlated with a diverse of diseases including cancer. On this regard, a strategy for targeting Wnt/β-catenin signaling has been employed in the discovery and development of antitumor agents. Herein, the evolution of Wnt signaling and the Wnt inhibitors derived from natural products were briefly summarized in the drug discovery of anticancer agents.

Isolation of Constituents with Nitric Oxide Synthase Inhibition Activity from Phryma leptostachya var. asiatica

Phytochemical studies were performed to identify the active principles of Phryma leptostachya var. asiatica (Phyrymaceae) for anti-inflammation. The anti-inflammatory activity was assessed by measuring the inhibition rate on nitric oxide (NO) formation in lipopolysaccharide (LPS)-activated macrophage 264.7 cells. Of the five compounds including ursolic acid, phrymarolin I, harpagide, haedoxancoside A, and acteoside isolated from this plant, ursolic acid showed the most prominent inhibition of NO formation. Therefore, ursolic acid may be the anti-inflammatory principle of Phryma leptostachya var. asiatica.

Analysis of Essential oil, Quantification of Six Glycosides, and Nitric Oxide Synthase Inhibition Activity in Caryopteris incana

Caryopteris incana (Verbenaceae) has been used to treat cough, arthritis, and eczema in Oriental medicine. The two fractions (CHCl₃- and BuOH fractions) and the essential oil of the plant material were subjected to the inducible nitric oxide synthase (iNOS) assay. The IC₅₀ of the CHCl₃ fraction and the essential oil on LPS-induced macrophage RAW 264.7 cells were 16.4 µg/mL and 23.08 µg/mL, respectively. On gas chromatography (GC)-mass spectroscopy (MS) analysis, twenty-five components representing 85.5% amount of total essential oil were identified. On the chromatogram, three main substances, trans-pinocarveol, cis-citral, and pinocarvone, occupied 18.8%, 13.5% and 18.37% of total peak area. Furthermore, by HPLC-UV analysis, six compounds including one iridoid (8-O-acetylharpagide)- and five phenylethanoid glycosides (caryopteroside, acteoside, phlinoside A, 6-O-caffeoylphlinoside, and leucosceptoside A) isolated from the BuOH fraction were quantified. The content of six compounds were shown as the following order: caryopteroside (162.35 mg/g) > 8-O-acetylharpagide (93.28 mg/g) > 6-O-caffeoylphlinoside (28.15mg/g) > phlinoside (22.60mg/g) > leucosceptoside A (16.87 mg) > acteoside (7.05 mg/g).

Relative risk of virulence factors in Candida-infected mouse

Candida albicans is one of the most frequently isolated fungal pathogens in human. Recently, the prevalence of candida infection has markedly increased, partially due to the increase of immunocompromised hosts. Proposed virulence factors of the pathogenic Candida are the ability to form hyphae to adhere to epithelial cell surfaces, and to secrete acid proteinases and phospholipases. We measured the relative cell surface hydrophobicity (CSH) and the ability of proteinase production (PROT), phospholipase production (PLase), adherence to host epithelium (ADH), and hyphal transition (Germ). The relative risk of virulence factors was analyzed by lethality test in murine model of hematogeneously disseminated candidal infection. According to Cox's proportional hazard analysis, the statistically significant virulence factors were PROT, ADH, and CSH. PROT was the highest risk factor of them. To evaluate the applicability for the diagnosis and treatment of Candidiasis, we examined the protective effect of the active and passive immunizations with the materials purified from virulence factors and antibodies to them in Candia-infected mice model. The mean survival times of active and passive immunized groups were slightly longer than those of non-immunized groups.

The Effect of Rabbit Serum on the Expression of Cell Surface Hydrophobicity in Candida albicans / 대한의진균학회지

No abstract available.

The presumptive identification of Candida albicans with germ tube induced by high temperature

For direct identification of Candida albicans from other Candida species, the chlamydospore formation and the mycelial transition induced by high temperature and by sera were examined in 198 Candida isolates. The germ tubes of C. albicans developed early at 30 min in high temperature-induction, but at 60 min in serum-induction. C. albicans generated germ tubes well at concentrations lower than 2 x 10(7) cells/ml, but the germ tube formation was markedly restrained at concentrations higher than 4 x 10(7) cells/ml. In a serum-free, yeast extract-peptone-dextrose (YEPD) medium, C. albicans grew as a yeast form at 30 degrees C and as a mycelial form at 35-42 degrees C. Mycelial development was maximal at 37 degrees C in serum and at 39 degrees C in YEPD. Germ tubes were formed within 30 min in YEPD at 39 degrees C, but after 60 min in serum at 37 degrees C. Our examination showed that the 39 degrees C-induced germ tube formation tests were very reliable (sensitivity 100%, specificity 100%) at discerning C. albicans from other Candida species. These results suggest that the high temperature-induced germ tube formation testing could be a useful identification method of C. albicans in clinical laboratories.