Biological & pharmaceutical bulletin
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The injury-induced intense stimulation of spinal cord neurons causes lysophosphatidic acid (LPA) biosynthesis. LPA(1) receptor activation causes demyelination and sprouting of dorsal root fibers, leading to an induction of synaptic reorganization underlying allodynia, in which innocuous (tactile) stimuli cause intense pain. ⋯ On the other hand, the LPA(3) receptor mediates microglia activation at the early stage after nerve injury and LPA-induced LPA biosynthesis. Thus, both the LPA(1) and LPA(3) receptors play key roles in the initiation step using a feed-forward system for neuropathic pain.
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We previously investigated the effects of an aqueous extract of maté (mate) tea, made from the leaves of Ilex paraguariensis, on the diabesity and metabolic syndrome features in a mouse model. Mate induced significant decreases in body weight (BW), body mass index, and food intake (FI). In this study, to verify the mode of action of mate on FI and consequently on BW, we examined the anorexic effects of mate on the appetite and satiety markers glucagon-like peptide 1 (GLP-1) and leptin in high-fat diet-fed ddY mice. ⋯ Mate induced significant increases in GLP-1 levels and leptin levels compared with the control. Acute administration of major constituents of mate showed significant increases in GLP-1 levels by dicaffeoyl quinic acids and matesaponins, and significant induction of satiety by caffeoyl quinic acids and caffeine in ddY mice. These findings suggest that mate may induce anorexic effects by direct induction of satiety and by stimulation of GLP-1 secretion and modulation of serum leptin levels.
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Daiokanzoto (DKT), a Kampo medicine that includes the combination of two crude drugs (rhubarb and glycyrrhiza), is clinically effective for constipation. The aim of this study is to clarify the influence of glycyrrhiza, three glycyrrhiza constituents (glycyrrhizin, liquiritin, and liquiritin apioside), and eight antibiotics on the purgative action of DKT, rhubarb, or sennoside A, a constituent of rhubarb, in mice. The purgative actions of rhubarb and sennoside A were significantly intensified when glycyrrhiza was co-administered orally to mice. ⋯ The effect of minocycline on the purgative action of sennoside A was lost when glycyrrhiza was co-administered. These results suggest that liquiritin and liquiritin apioside contribute as active substances for the purgative action of DKT, and some antibiotics reduce the purgative action of DKT and sennoside A. Furthermore, glycyrrhiza has the ability to recover the purgative action of sennoside A suppressed by minocycline via an unknown mechanism.
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The development of a simple, easy-to-use, and noninvasive vaccination system is in high demand. For transcutaneous immunization (TCI), we previously reported that a hydrogel patch was an effective TCI device that accelerates antigen penetration through the stratum corneum in mouse and rat models. ⋯ In addition, proteins delivered into the skin by the hydrogel patch retained their activity, suggesting that the hydrogel patch is applicable for the delivery of therapies for other diseases as well. On the basis of these results, translational research in human is now in progress.
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Transient receptor potential vanilloid 1 (TRPV1) is primarily expressed in central and peripheral terminals of non-myelinated primary afferent neurons. We previously showed that AS1928370, a novel TRPV1 antagonist that can prevent ligand-induced activation but not proton-induced activation, ameliorates neuropathic pain in rats without hyperthermic effect. In this study, we investigated its analgesic profile in mice. ⋯ Intrathecal administration of AS1928370 (30 µg/body) also significantly suppressed mechanical allodynia. In addition, AS1928370 showed no effect on locomotor activity up to 30 mg/kg p.o. These results suggest that spinal TRPV1 has an important role in the transmission of neuropathic pain and that the central nervous system (CNS) penetrant TRPV1 receptor antagonist AS1928370 is a promising candidate for treating neuropathic pain.