Department of Pharmacognosy, Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-Ku, Nagoya, Aichi, 468-8503, Japan.
Department of Pharmacognosy, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-Ku, Nagoya, Aichi, 468-8503, Japan.
J Nat Med. 2023 Mar;77(2):352-362. doi: 10.1007/s11418-023-01683-0. Epub 2023 Feb 3.
Hochuekkito (HET) is a Kampo prescription, used for the clinical treatment of skin diseases such as atopic dermatitis (AD), in Japan. Oral administration of HET exerts anti-allergic effects in an experimental dermatitis mice model and in patients with atopic dermatitis; however, the mechanism underlying the anti-allergic effects of HET is still unclear. Therefore, we investigated the immunopharmacological properties of the anti-allergic actions of HET using a 2,4,6-trinitrochlorobenzene (TNCB)-induced murine contact hypersensitivity (CHS) model and adoptive cell transfer experiments. Oral administration of HET (1.4 g/kg) exhibited anti-allergic effects in a TNCB-induced CHS model via activation of Tregs; this activation was observed even without antigen sensitization in donor mice. Activation was dependent on the duration of HET administration and required at least 4 days of dosing. In addition, the anti-allergic effects of HET through the activation of Tregs were not antigen specific. Flow cytometry results indicated that the proportion of CD4CD25Foxp3 cells in the splenic lymphocytes increased after oral administration of HET. Therefore, oral administration of HET induced both inducible regulatory T cells (iTregs) and thymus-derived naturally occurring regulatory T cells (nTregs). Ginseng radix and Bupleuri radix were involved in the anti-allergic actions of HET through the induction and/or activation of Tregs; Bupleuri radix participated in the activation of nTregs. In conclusion, our findings suggest that HET exerts the anti-allergic effects through the induction and/or activation of Tregs. These findings elucidate the usefulness of HET as an immunomodulator.
六合定中丸（HET）是一种汉方药，用于治疗特应性皮炎（AD）等皮肤病。在实验性皮炎小鼠模型和特应性皮炎患者中，口服 HET 具有抗过敏作用；然而，HET 抗过敏作用的机制尚不清楚。因此，我们使用 2,4,6-三硝基氯苯（TNCB）诱导的小鼠接触超敏反应（CHS）模型和过继细胞转移实验研究了 HET 的免疫药理学特性。口服 HET（1.4 g/kg）通过激活 Tregs 在 TNCB 诱导的 CHS 模型中表现出抗过敏作用；即使在供体小鼠中没有抗原致敏的情况下，也观察到这种激活。激活依赖于 HET 给药的持续时间，至少需要 4 天的给药。此外，HET 通过激活 Tregs 发挥的抗过敏作用不是抗原特异性的。流式细胞术结果表明，口服 HET 后，脾淋巴细胞中 CD4CD25Foxp3 细胞的比例增加。因此，口服 HET 诱导了诱导性调节性 T 细胞（iTregs）和胸腺源性天然调节性 T 细胞（nTregs）。人参根和柴胡根通过诱导和/或激活 Tregs 参与了 HET 的抗过敏作用；柴胡根参与了 nTregs 的激活。总之，我们的研究结果表明，HET 通过诱导和/或激活 Tregs 发挥抗过敏作用。这些发现阐明了 HET 作为免疫调节剂的有用性。
