Effect of some Kampo medicines, including Tokaku-joki-to (Tao-He-Cheng-Qi-Tang), on IgE-mediated triphasic skin reaction in passively sensitized mice

Previous studies have reported that the mice passively sensitized with anti-DNP IgE antibody exhibited IgE-mediated biphasic cutaneous reaction with an immediate phase response (IPR) at 1 h and a late phase response (LPR) at 24 h after the challenge of DNFB (dinitrofluorobenzene) . We recently found that the third phase inflammatory response with intense and persisting infiltration of eosinophils, named very late phase response (vLPR) , was induced following IPR and LPR in response to DNFB in passively sensitized mice, and that the peak response of vLPR was on the 8^ day after the challenge. The inhibitory effect of Kampo medicines on the triphasic cutaneous inflammatory reaction was divided into several groups in terms of their inhibition rate of ear swelling. Among the formulations, Tokaku-joki-to (Tao-He-Cheng-Qi-Tang) was effective at inhibiting IPR, LPR and vLPR ( +/+/+ group) and scratching behavior in IPR. The Inhibitory effect of Tokaku-joki-to on triphasic cutaneous reaction primarily depends on its composed crude drugs, Glycyrrhizae Radix and Cinnamomi Cortex. These findings indicate that Tokaku-joki-to formulation is usefull for the inhibition of cutaneous inflammatory diseases. 抗DNP IgE抗体で受動感作したマウスの耳介にDNFB(ジニトロフルオロベンゼン)を塗布することにより,1時問およぴ24時間目をピークとする即時相反応(IPR)およぴ遅発相反応(LPR)からなるIgE介在二相性皮膚反応を示すことがすでに知られている。我々は最近,この受動感作マウスにおいてDNFBによる反応惹起後にIPR,LPRに続く,三相目の強い炎症性反応を見出し,超遅発相反応(vLPR)と名付けた。これは抗原塗布から8日目をピークとする,著明かつ持続的な好酸球の浸潤を伴う腫脹反応である。種々の漢方方剤を用いて,この三相性皮膚反応に対する抑制効果を検討した結果,各相の耳介腫脹の抑制率に基づき,いくつかのグループに分類された。検討した方剤中,桃核承気湯はIPR,LPR,vLPRの三相反応に対して抑制を示し(+/+/+群),さらにIPRで観察される耳介の掻き行動(痒みの指標と考えられる)を抑制した。桃核承気湯の三相性皮膚反応に対する抑制効果の発現は,主として構成生薬である甘草およぴ桂皮に基づくことが示唆された。これらの知見から,漢方方剤:桃核承気湯が炎症性皮膚疾患に有効であることが示された

Human Molecular Chaperone Hsp60 and Its Apical Domain Suppress Amyloid Fibril Formation of α-Synuclein

Heat shock proteins play roles in assisting other proteins to fold correctly and in preventing the aggregation and accumulation of proteins in misfolded conformations. However, the process of aging significantly degrades this ability to maintain protein homeostasis. Consequently, proteins with incorrect conformations are prone to aggregate and accumulate in cells, and this aberrant aggregation of misfolded proteins may trigger various neurodegenerative diseases, such as Parkinson’s disease. Here, we investigated the possibilities of suppressing α-synuclein aggregation by using a mutant form of human chaperonin Hsp60, and a derivative of the isolated apical domain of Hsp60 (Hsp60 AD(Cys)). In vitro measurements were used to detect the effects of chaperonin on amyloid fibril formation, and interactions between Hsp60 proteins and α-synuclein were probed by quartz crystal microbalance analysis. The ability of Hsp60 AD(Cys) to suppress α-synuclein intracellular aggregation and cytotoxicity was also demonstrated. We show that Hsp60 mutant and Hsp60 AD(Cys) both effectively suppress α-synuclein amyloid fibril formation, and also demonstrate for the first time the ability of Hsp60 AD(Cys) to function as a mini-chaperone inside cells. These results highlight the possibility of using Hsp60 AD as a method of prevention and treatment of neurodegenerative diseases

Continuous-Flow Synthesis of N-Succinimidyl 4-[18F]fluorobenzoate Using a Single Microfluidic Chip

In the field of positron emission tomography (PET) radiochemistry, compact microreactors provide reliable and reproducible synthesis methods that reduce the use of expensive precursors for radiolabeling and make effective use of the limited space in a hot cell. To develop more compact microreactors for radiosynthesis of 18F-labeled compounds required for the multistep procedure, we attempted radiosynthesis of N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) via a three-step procedure using a microreactor. We examined individual steps for [18F]SFB using a batch reactor and microreactor and developed a new continuous-flow synthetic method with a single microfluidic chip to achieve rapid and efficient radiosynthesis of [18F]SFB. In the synthesis of [18F]SFB using this continuous-flow method, the three-step reaction was successfully completed within 6.5 min and the radiochemical yield was 64 ± 2% (n = 5). In addition, it was shown that the quality of [18F]SFB synthesized on this method was equal to that synthesized by conventional methods using a batch reactor in the radiolabeling of bovine serum albumin with [18F]SFB