Serum metabolome analysis reveals medicinal fungi Phellinus igniarius ameliorated type 2 diabetes mellitus indications in rats via modulation of amino acid and carbohydrate metabolism.

Medicinal fungi Phellinus igniarius exhibited hypoglycemic effects; however, the protective mechanisms of P. igniarius on type 2 diabetes are not yet fully understood. Herein, the anti-diabetic effect of P. igniarius was investigated via gas chromatography-mass spectrometry (GC/MS)-based metabolome analysis. The rats were divided into normal group; model group; positive group; and groups treated with low, medium, and high dose of P. igniarius. After the treatments, a significant decrease in blood glucose concentration was observed. The levels of total cholesterol and triglyceride were dramatically decreased, whereas the level of insulin was increased. Multivariate statistical analysis revealed 31 differential endogenous metabolites between model group and normal group. A total of 14, 28, and 31 biomarkers were identified for low, medium, and high dose of P. igniarius treated groups, respectively. Twenty-one of the biomarkers were validated by using standard substances. The linear correlation coefficients ranged from 0.9990 to 1.0000. The methodology exhibited good repeatability, recoveries, and stability. The major intervened metabolic pathways covered glyoxylate and dicarboxylic acid metabolism; alanine, aspartate, and glutamate metabolism; and glycine, serine, and threonine metabolism. Our metabolome analysis has provided insights into the underlying mechanism of P. igniarius on type 2 diabetes.

Synergistic anti-oxidant and anti-inflammatory effects of ceria/resatorvid co-decorated nanoparticles for acute lung injury therapy.

BACKGROUND: Acute lung injury (ALI) is a critical inflammatory response syndrome that rapidly develops into acute respiratory distress syndrome (ARDS). Currently, no effective therapeutic modalities are available for patients with ALI/ARDS. According to recent studies, inhibiting both the release of pro-inflammatory cytokines and the formation of reactive oxygen species (ROS) as early as possible may be a promising therapy for ALI. RESULTS: In this study, a ROS-responsive nano-delivery system based on oxidation-sensitive chitosan (Ox-CS) was fabricated for the simultaneous delivery of Ce NPs and RT. The in vitro experiments have shown that the Ox-CS/Ceria-Resatorvid nanoparticles (Ox-CS/CeRT NPs) were rapidly and efficiently internalised by inflammatory endothelial cells. Biological evaluations validated the significant attenuation of ROS-induced oxidative stress and cell apoptosis by Ox-CS/CeRT NPs, while maintaining mitochondrial function. Additionally, Ox-CS/CeRT NPs effectively inhibited the release of pro-inflammatory factors. After intraperitoneal (i.p.) administration, Ox-CS/CeRT NPs passively targeted the lungs of LPS-induced inflamed mice and released the drug activated by the high ROS levels in inflammatory tissues. Finally, Ox-CS/CeRT NPs significantly alleviated LPS-induced lung injury through inhibiting both oxidative stress and pro-inflammatory cytokine expression. CONCLUSIONS: The created Ox-CS/CeRT NPs could act as a prospective nano-delivery system for a combination of anti-inflammatory and anti-oxidant therapy of ALI.

Doxofylline ameliorates liver fibrosis by regulating the ferroptosis signaling pathway.

Liver fibrosis, a compensatory repair response to chronic liver injury, is caused by various pathogenic factors, and hepatic stellate cell (HSC) activation and phenotypic transformation are regarded as key events in its progression. Ferroptosis, a novel form of programmed cell death, is also closely related to different pathological processes, including those associated with liver diseases. Here, we investigated the effect of doxofylline (DOX), a xanthine derivative with potent anti-inflammatory activity, on liver fibrosis as well as the associated mechanism. Our results indicated that in mice with CCl4-induced liver fibrosis, DOX attenuated hepatocellular injury and the levels of liver fibrosis indicators, inhibited the TGF-ß/Smad signaling pathway, and significantly downregulated the expression of HSC activation markers, both in vitro and in vivo. Furthermore, inducing ferroptosis in activated HSCs was found to be critical for its anti-liver fibrosis effect. More importantly, ferroptosis inhibition using the specific inhibitor, deferoxamine (DFO) not only abolished DOX-induced ferroptosis, but also led to resistance to the anti-liver fibrosis effect of DOX in HSCs. In summary, our results showed an association between the protective effect of DOX against liver fibrosis and HSC ferroptosis. Thus, DOX may be a promising anti-hepatic fibrosis agent.