2 research outputs found
Tamarixetin Exhibits Anti-inflammatory Activity and Prevents Bacterial Sepsis by Increasing IL-10 Production
Sepsis is a systemic inflammatory
response to pathogenic infection
that currently has no specific pharmaceutical interventions. Instead,
antibiotics administration is considered the best available option,
despite increasing drug resistance. Alternative strategies are therefore
urgently required to prevent sepsis and strengthen the host immune
system. One such option is tamarixetin (4′-<i>O</i>-methylquercetin), a naturally occurring flavonoid derivative of
quercetin that protects against inflammation. The purpose of this
study was to determine whether the anti-inflammatory effects of tamarixetin
protect against the specific inflammatory conditions induced in lipopolysaccharide
(LPS) or <i>Escherichia coli</i> K1 models of sepsis. Our
study showed that tamarixetin reduced the secretion of various inflammatory
cytokines by dendritic cells after activation with LPS. It also promoted
the secretion of the anti-inflammatory cytokine interleukin (IL)-10
and specifically increased the population of IL-10-secreting immune
cells in LPS-activated splenocytes. Tamarixetin showed general anti-inflammatory
effects in mouse models of bacterial sepsis and decreased bacteria
abundance and endotoxin levels. We therefore conclude that tamarixetin
has superior anti-inflammatory properties than quercetin during bacterial
sepsis. This effect is associated with an increased population of
IL-10-secreting immune cells and suggests that tamarixetin could serve
as a specific pharmaceutical option to prevent bacterial sepsis
Selective delivery of PLXDC1 small interfering RNA to endothelial cells for anti-angiogenesis tumor therapy using CD44-targeted chitosan nanoparticles for epithelial ovarian cancer
<p>Angiogenesis plays an essential role in the growth and metastasis of tumor cells, and the modulation of angiogenesis can be an effective approach for cancer therapy. We focused on silencing the angiogenic gene PLXDC1 as an important factor for anti-angiogenesis tumor therapy. Herein, we developed PLXDC1 small interfering siRNA (siRNA)-incorporated chitosan nanoparticle (CH-NP/siRNA) coated with hyaluronic acid (HA) to target the CD44 receptor on tumor endothelial cells. This study aimed to improve targeted delivery and enhance therapeutic efficacy for tumor anti-angiogenesis. The HA-CH-NP/siRNA was 200 ± 10 nm in size with a zeta potential of 26.4 mV. The loading efficiency of siRNA to the HA-CH-NP/siRNA was up to 60%. The selective binding of HA-CH-NP/siRNA to CD44-positive tumor endothelial cells increased by 2.1-fold compared with that of the CD44 nontargeted CH-NP/siRNA. PLXDC1 silencing by the HA-CH-NP/siRNA significantly inhibited tumor growth in A2780 tumor-bearing mice compared with that in the control group (<i>p</i> < .01), and mRNA expression of PLXDC1 was significantly reduced in the HA-CH-NP/siRNA-treated group. Furthermore, treatment with HA-CH-NP/siRNA resulted in significant inhibition of cell proliferation (<i>p</i> < .001), reduced microvessel density (<i>p</i> < .001), and increased cell apoptosis (<i>p</i> < .001). This study demonstrates that HA-CH-NP/siRNA is a highly selective delivery platform for siRNA, and has broad potential to be used in anti-angiogenesis tumor therapy.</p