No abstract

The purpose of this research was to evaluate whether maltol could protect from hepatic injury induced by carbon tetrachloride (CCl4) in vivo by inhibition of apoptosis and inflammatory responses. In this work, maltol was administered at a level of 100 mg/kg for 15 days prior to exposure to a single injection of CCl4 (0.25%, i.p.). The results clearly indicated that the intrapulmonary injection of CCl4 resulted in a sharp increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) activities, tumor necrosis factor-α (TNF-α), irreducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB) and interleukin-1β (IL-1β) levels. Histopathological examination demonstrated severe hepatocyte necrosis and the destruction of architecture in liver lesions. Immunohistochemical staining and western blot analysis suggested an accumulation of iNOS, NF-κB, IL-1β and TNF-α expression. Maltol, when administered to mice for 15 days, can significantly improve these deleterious changes. In addition, TUNEL and Hoechst 33258 staining showed that a liver cell nucleus of a model group diffused uniform fluorescence following CCl4 injection. Maltol pretreatment groups did not show significant cell nuclear condensation and fragmentation, indicating that maltol inhibited CCl4-induced cell apoptosis. By evaluating the liver catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) activity, and further using a single agent to evaluate the oxidative stress in CCl4-induced hepatotoxicity by immunofluorescence staining, maltol dramatically attenuated the reduction levels of hepatic CAT, GSH and SOD, and the over-expression levels of CYP2E1 and HO-1. In the mouse model of CCl4-induced liver injury, we have demonstrated that the inflammatory responses were inhibited, the serum levels of ALT and AST were reduced, cell apoptosis was suppressed, and liver injury caused by CCl4 was alleviated by maltol, demonstrating that maltol may be an efficient hepatoprotective agent.

No abstract

The Wei Pi Xiao (WPX) decoction, based on the theory of traditional Chinese medicine, has been widely used for the treatment of gastric precancerous lesions (GPL). Although WPX is known to be effective for the treatment of GPL, its active ingredients, cellular targets, and the precise molecular mechanism of action are not known. This study aimed to identify the multiple mechanisms of action of the WPX decoction in the treatment of GPL. The active compounds, drug targets, and the key pathways involved in the therapeutic effect of WPX in the treatment of GPL were analyzed by an integrative analysis pipeline. The information pertaining to the compounds present in WPX and their disease targets was obtained from TCMSP and GeneCards, respectively. The mechanisms underlying the therapeutic effect of WPX were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A total of 82 bioactive compounds and 146 related targets were identified in this study. Following target analyses, the targets were further mapped to 26 key biological processes and 21 related pathways to construct a target-pathway network and an integrated GPL pathway. The study demonstrated that the WPX formula primarily treats the dysfunctions of GPL arising from cell proliferation, apoptosis, and mucosal inflammation, which offered a novel insight into the pathogenesis of GPL and revealed the molecular mechanism underlying the therapeutic effects of the WPX formula in GPL. This study offers a novel approach for the systematic investigation of the mechanisms of action of herbal medicines, which will provide an impetus to the GPL drug development pipeline.

Methylmercury (MeHg) is a ubiquitous environmental toxin that causes neurologic and developmental diseases. Oxidative damage and excitotoxicity are putative mechanisms, which underlie MeHg-induced neurotoxicity. In this study, the cross-talk between the oxidative damage and excitotoxicity pathways and the protective effects of riluzole in the rat cortex were explored. Rats were injected with MeHg and/or riluzole, and cold vapor atomic fluorescence spectrometry, hematoxylin and eosin staining, flow cytometry, fluorescence assays, spectrophotometry, real-time PCR, and Western blotting were used to evaluate neurotoxicity. The present study showed that (1) MeHg accumulated in the cerebral cortex and caused pathology. (2) MeHg caused oxidative damage by inducing glutathione (GSH) depletion, reactive oxygen species (ROS) production, inhibition of antioxidant enzyme activity, and alteration of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. (3) MeHg disrupted the glutamate transporters (GluTs), glutamate-glutamine cycle, and N-methyl-D-aspartate receptor expression and induced excitotoxicity. (4) Excitotoxicity resulted in disruption of GSH synthesis, calcium overloading, oxidative damage, and excessive ROS production. (5) Pretreatment with riluzole antagonized MeHg neurotoxicity by down regulating cross-talk between the oxidative damage and excitotoxicity pathways. In conclusion, the cross-talk between the oxidative damage and excitotoxicity pathways caused by MeHg exposure was linked by GluTs and calcium and inhibited by riluzole treatment.