Natural compound Oblongifolin C confers gemcitabine resistance in pancreatic cancer by downregulating Src/MAPK/ERK pathways.

Gemcitabine (GEM)-induced drug resistance is the major reason for the failure of chemotherapy in pancreatic cancer (PC). In this study, we found that Oblongifolin C (OC) efficiently inhibited PC cell proliferation by inducing G0/G1 arrest and apoptosis. Also, our mechanism study demonstrated that OC re-sensitized the GEM-resistant PC cells through the ubiquitin-proteasome-dependent degradation of Src, and then downregulating the MAPK pathway. Knockdown of Src plus OC resulted in a greater inhibitory effect in GEM-resistant PC cells. In contrast, Src overexpression reversed OC-mediated chemosensitization, thereby implicating Src in the action of OC. Moreover, our in vivo study showed that OC suppressed the tumor growth via the downregulation of Src, and enhanced the chemosensitivity of GEM-resistant PC to GEM. Overall, our results have revealed that OC is applicable as a promising agent for overcoming GEM-resistant PC, especially with aberrant Src expression.

The natural compound nujiangexanthone A suppresses mast cell activation and allergic asthma.

Mast cells play an important role in allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. The genus Garcinia of the family Guttiferae is well known as a prolific source of polycyclic polyprenylated acylphloroglucinols and bioactive prenylated xanthones, which exhibit various biological activities including antibacterial, antifungal, anti-inflammatory, antioxidant, and cytotoxic effects. Nujiangexanthone A (N7) is a novel compound isolated from the leaves of Garcinia nujiangensis. In this paper, we sought to determine the anti-allergic and anti-inflammation activity of N7 in vivo and its mechanism in vitro. We found N7 suppressed IgE/Ag induced mast cell activiation, including degranulation and production of cytokines and eicosanoids, through inhibiting Src kinase activity and Syk dependent pathways. N7 inhibited histamine release, prostaglandin D2 and leukotriene C4 generation in mast cell dependent passive cutaneous anaphylaxis animal model. We also found N7 inhibited the IL-4, IL-5, IL-13 and IgE levels in ovalbumin-induced asthma model. Histological studies demonstrated that N7 substantially inhibited OVA-induced cellular infiltration and increased mucus production in the lung tissue. Our study reveals the anti-allergic function of N7, thereby suggesting the utility of this compound as a possible novel agent for preventing mast cell-related immediate and delayed allergic diseases.

Inhibitory effect of oblongifolin C on allergic inflammation through the suppression of mast cell activation.

Oblongifolin C (OC), a natural small molecule compound extracted from Garcinia yunnanensis Hu, has been previously shown to have anti-cancer effect, but the anti-allergic effect of OC has not yet been investigated. The aim of the present study is to determine the anti-allergic effect of OC on IgE/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and on the passive systemic anaphylaxis (PSA) reaction in mice. OC clearly suppressed cyclooxygenase-2 (COX-2)-dependent prostaglandin D2 (PGD2) generation as well as leukotriene C4 (LTC4) generation and the degranulation reaction in IgE/Ag-stimulated BMMCs. Biochemical analyses of the IgE/Ag-mediated signaling pathways showed that OC suppressed the phosphorylation of phospholipase Cγ1 (PLCγ1)-mediated intracellular Ca(2+) influx and the nuclear factor-κB (NF-κB) pathway, as well as the phosphorylation of mitogen-activated protein (MAP) kinases. Although OC did not inhibit the phosphorylation of Fyn, Lyn, and Syk, it directly inhibited the tyrosine kinase activity in vitro. Moreover, oral administration of OC inhibited the IgE-induced PSA reaction in a dose-dependent manner. Taken together, the present study provides new insights into the anti-allergic activity of OC, which could be a promising candidate for allergic therapy.

Distinguishing Radix Angelica sinensis from different regions by HS-SFME/GC-MS.

An automated headspace solvent free microextraction (HS-SFME) based gas chromatography/mass spectrometry (GC/MS) was developed for discrimination of Radix Angelica sinensis (RAS) from different cultivation regions. The MS data were subjected to principal component analysis (PCA) and hierarchical clustering analysis (HCA) to rapidly find the potential characteristic components of RAS from top-geoherb region and non top-geoherb region. Totally, fifty-one volatile organic compounds (VOCs) were identified, in which ß-ocimene, α-pinene, 3-methylbutanal, heptanes, butanal were identified as potential markers for distinguishing RAS from top-geoherb region and non top-geoherb region. Sulphur dioxide was detected in some commercial RAS samples, which implied that sulphur-fumigation might be the main reason for the quality inconsistencies of commercial RAS samples. These results suggested that RAS from top-geoherb region and non-top geoherb region could be discriminated by the method. And characteristic chemical markers found in current study can be used for ensuring consistent quality of top-geoherb of RAS.