Biological & pharmaceutical bulletin
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In this study, using a special diet-induced mouse model of atopic dermatitis, we tested the effect of chitosan-containing lotion (CL) on itch-related scratching associated with barrier-disrupted dry skin. HR-1 hairless mice fed a special diet exhibited apparent dry skin symptoms characterized by decreased skin hydration and increased transepidermal water loss. In the special diet-fed mice, scratching behavior was markedly enhanced for 60 min after oral administration of ethanol. ⋯ Although the decreased skin hydration was improved even by the vehicle, the increased transepidermal water loss was resolved only by CL. Skin surface temperature was much more reduced in CL-treated mice than in vehicle-treated mice. Collectively, CL has an antipruritic effect, which could be partly explained by recovery of skin barrier function and cooling of the skin.
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Gelsemium elegans BENTH and its crude extract are widely used to treat pain in China despite its apparent toxicity. The analgesic effects of gelsenicine, an active component of G. elegans, however, have not been reported. The current study examined potential analgesic effects of subcutaneously injected gelsenicine using acetic acid-induced writhing, formalin-induced nociceptive behavior, and thermal hyperalgesia caused by chronic constriction injury (CCI) in mice. ⋯ The ED(50), for either the inflammatory pain (10.4 µg/kg for writhing test, 7.4 µg/kg for formalin test) or neuropathic pain (9.8 µg/kg for thermal hyperalgesia caused by CCI model), was far below the LD(50) (95% confidence interval at 100-200 µg/kg). Repeated subcutaneous injections of gelsenicine in CCI mice led to sustained attenuation of neuropathic pain after drug discontinuation. These results revealed that gelsenicine could be used safely to attenuate both inflammatory and neuropathic pain.
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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 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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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.