Diverse Possibilities of Si-Based Agent, a Unique New Antioxidant.

Antioxidant therapy is an effective approach for treating diseases in which oxidative stress is involved in the onset of symptoms. This approach aims to rapidly replenish the antioxidant substances in the body when they are depleted due to excess oxidative stress. Importantly, a supplemented antioxidant must specifically eliminate harmful reactive oxygen species (ROS) without reacting with physiologically beneficial ROS, which are important to the body. In this regard, typically used antioxidant therapies can be effective, but may cause adverse effects due to their lack of specificity. We believe that Si-based agents are epoch-making drugs that can overcome these problems associated with current antioxidative therapy. These agents alleviate the symptoms of oxidative-stress-associated diseases by generating large amounts of the antioxidant hydrogen in the body. Moreover, Si-based agents are expected to be highly effective therapeutic drug candidates because they have anti-inflammatory, anti-apoptotic, and antioxidant effects. In this review, we discuss Si-based agents and their potential future applications in antioxidant therapy. There have been several reports of hydrogen generation from silicon nanoparticles, but unfortunately, none have been approved as pharmaceutical agents. Therefore, we believe that our research into medical applications using Si-based agents is a breakthrough in this research field. The knowledge obtained thus far from animal models of pathology may greatly contribute to the improvement of existing treatment methods and the development of new treatment methods. We hope that this review will further revitalize the research field of antioxidants and lead to the commercialization of Si-based agents.

Yokukansan-induced reduction of ethanol preference is associated with antagonism of 5-HT3 receptors.

BACKGROUND: We recently reported that alkaloids in Uncaria hook (a constituent of yokukansan) contribute to antagonism of 5-HT3 receptors. Many studies have reported that 5-HT3 receptor antagonists reduce alcohol preference. However, the effect of yokukansan on alcohol preference is not clear. PURPOSE: This study was performed to investigate the direct effect of yokukansan on alcohol preference and the effect of 5-HT3 receptors on the preference. STUDY DESIGN: We examined ethanol preference effected by yokukansan. Next, we analyzed the contribution of 5-HT3 receptors to the effect of yokukansan. METHODS: Ethanol preference was measured using the two-bottle preference test in mice fed with or without yokukansan diet. Next, the contribution of 5-HT3 receptors to ethanol preference was investigated using 5-HT3 receptor-deficient mice. RESULTS: Reduction of ethanol preference by yokukansan was not observed using 5-HT3 receptor deficient mice. CONCLUSION: Yokukansan contributes to reduced ethanol preference and antagonism of 5-HT3 receptors is associated with the effect.

Yokukansan contains compounds that antagonize the 5-HT3 receptor.

BACKGROUND: We recently focused on alkaloids in Uncaria hook (a constituent of the Kampo medicine, yokukansan) and identified the pharmacological action of geissoschizine methyl ether on several G protein-coupled receptors. However, the functions of other identified alkaloids in Uncaria hook, including hirsutine, hirsuteine, rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine, are not clear. PURPOSE: To evaluate the effect of seven alkaloids in Uncaria hook (hirsutine, hirsuteine, rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine and geissoschizine methyl ether) on the hydroxytryptamine type-3 (5-HT3) receptor ion channel. STUDY DESIGN: We examined the effect of these alkaloids on the current of human 5-HT3 receptors expressed in Xenopus laevis oocytes. METHODS: The human 5-HT3A subunit alone for the 5-HT3A receptor, or 5-HT3A and 5-HT3B subunits for the 5-HT3AB receptor, were expressed in Xenopus laevis oocytes. The 5-HT current was measured with or without alkaloid application using a two-electrode voltage clamp. RESULTS: Each alkaloid, except for geissoschizine methyl ether, weakly inhibited the 5-HT-mediated 5-HT3A and/or 5-HT3AB receptor current, but co-application of these seven alkaloids inhibited the current strongly. CONCLUSION: Each alkaloid contributes to antagonism of the 5-HT3 receptor.

Distinct expression of cold receptors (TRPM8 and TRPA1) in the rat nodose-petrosal ganglion complex.

TRPM8 and TRPA1 are cold-activated transient receptor potential (TRP) cation channels. TRPM8 is activated by moderate cooling, while TRPA1 is activated by extreme, noxious cold temperatures. These cold receptors are expressed in different subpopulations of primary afferent neurons. TRPA1 is co-expressed in a subpopulation of somatosensory neurons expressing TRPV1, which is activated by heat. However, the distribution and co-expression of these channels in the nodose-petrosal ganglion complex, which contains the jugular (JG), petrosal (PG), and nodose ganglia (NG) (mainly involved in putative somatic, chemo- and somato-sensation, and somato and visceral sensation, respectively), remain unknown. Here, we conducted in situ hybridization analysis of the rat nodose-petrosal ganglion complex using specific riboprobes for TRPM8, TRPA1, and TRPV1 to compare the features of the cranial sensory ganglia. Hybridization signals for TRPA1 were diffusely observed throughout these ganglia, whereas TRPM8 transcripts were seen in the JG and PG but not in the NG. We retrogradely labeled cranial nerve X with Fast Blue (fluorescent dye) and found TRPM8 transcripts in the jugular-vagal ganglion but not the NG neurons. TRPA1 transcripts were not detected in TRPM8-expressing neurons but were present in the subpopulation of TRPV1-expressing visceral sensory neurons. Taken together, these findings support that in the vagal system the expression of cold-activated TRP channels differs between nodose- and jugular-ganglion neurons suggesting different mechanisms of cold-transduction and that the TRPA1 distribution is consistent with its proposed function as a cold-sensing receptor in the visceral system.