Syndecan-4 (SDC4) functions as a major endogenous membrane-associated receptor and widely regulates cytoskeleton, cell adhesion, and cell migration in human tumorigenesis and development, which represents a charming anti-cancer therapeutic target. Here, SDC4 was identified as a direct cellular target of small-molecule bufalin with anti-hepatocellular carcinoma (HCC) activity. Mechanism studies revealed that bufalin directly bond to SDC4 and selectively increased SDC4 interaction with substrate protein DEAD-box helicase 23 (DDX23) to induce HCC genomic instability. Meanwhile, pharmacological promotion of SDC4/DDX23 complex formation also inactivated matrix metalloproteinases (MMPs) and augmented p38/JNK MAPKs phosphorylation, which are highly associated with HCC proliferation and migration. Notably, specific knockdown of SDC4 or DDX23 markedly abolished bufalin-dependent inhibition of HCC proliferation and migration, indicating SDC4/DDX23 signaling axis is highly involved in the HCC process. Our results indicate that membrane-spanning proteoglycan SDC4 is a promising druggable target for HCC, and pharmacological regulation of SDC4/DDX23 signaling axis with small-molecule holds great potential to benefit HCC patients.
A simple method for separation of matrine and oxymatrine from Sophora fl avescens was developed with cation exchange resin coupled with macroporous resin. Based on the adsorption characteristics of matrine and oxymatrine, 001×732 cation exchange resin was used to absorb target alkaloids for removing most of the foreign matter, while BS-65 macroporous resin was chosen to purify these alkaloids. The result showed that the equilibrium adsorption data of matrine and oxymatrine on 001×732 resin and BS-65 resin at 30 o C was fi tted to Langmuir isotherm and Freundlich isotherm, respectively. The contents of matrine and oxymatrine were increased from 0.73% and 2.2% in the crude extract of the root of Sophora fl avescens to 67.2% and 66.8% in the fi nal eluent products with the recoveries of 90.3% and 86.9%, respectively.
Two previously undescribed dibenzocyclooctadiene lignans, named sieverlignans D–E (1-2), as well as eight known ones (3-10), were isolated from the aerial parts of Artemisia sieversiana. Their structures were elucidated from extensive spectroscopic analysis, including HRMS, NMR and circular dichroism experiments. This study is the first to report dibenzocyclooctadiene lignans in the genus Artemisia and this plant. All the compounds were evaluated for their anti-neuroinflammatory effects on the lipopolysaccharides (LPS)-induced nitric oxide production in BV-2 murine microglial cells. Compounds 1 and 6 exhibited the moderate activity with their IC50 values of 47.7 and 21.9 μM, compared to a positive control quercetin with the IC50 value of 16.0 μM.
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