Department of Clinical Research, Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
Center for Kampo Medicine, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
J Smooth Muscle Res. 2022;58:78-88. doi: 10.1540/jsmr.58.78.
BACKGROUND/AIMS: Gastroprokinetic agents are used for patients with postoperative ileus (POI), and the Japanese traditional herbal medicine daikenchuto (DKT) is one such agent used in the clinical setting. POI is caused by inflammation. DKT and rikkunshito have anti-inflammatory abilities in addition to their gastroprokinetic effects. The efficacy of Kampo formulations, including hangekobokuto (HKT), in patients with POI has been reported recently. Several authors have described the efficacy of honokiol, the primary component of Magnoliae Cortex, in HKT in mouse models of POI. We therefore analyzed the effect of HKT on POI model mice to determine the similarities in the mechanism of action between HKT and DKT.
HKT was administered orally to each mouse before and after intestinal manipulation was performed on the distal ileum. The gastrointestinal transit in vivo, leukocyte infiltration, and levels of inflammatory mediators, such as cytokines and chemokines, were analyzed.
HKT significantly inhibited the infiltration of neutrophils and macrophages and led to the recovery of delayed intestinal transit. In addition, it significantly decreased inducible nitric oxide synthase (iNOS) as well as honokiol levels, suggesting anti-inflammatory activity. However, it did not inhibit the increase in levels of interleukin (IL)-1beta and IL-6, which are related to iNOS induction. In contrast, HKT increased levels of nerve growth factor (NGF) and suppressed those of nuclear factor-κB (NFκB), which are related to iNOS induction, suggesting the possibility of a neuronal anti-inflammatory mechanism.
HKT exerted a POI-relieving effect similar to DKT in a murine POI model, and findings suggest that it may exert its anti-inflammatory activity through NGF.
背景/目的：胃肠动力药物用于术后肠梗阻（POI）患者，日本传统草药大建中汤（DKT）就是一种在临床中使用的药物。POI 是由炎症引起的。DKT 和利气除满汤除了具有胃肠动力作用外，还有抗炎作用。最近有报道称，包括黄荆子（HKT）在内的汉方制剂对 POI 患者有效。几位作者描述了厚朴的主要成分厚朴酚在 POI 小鼠模型中对 HKT 的功效。因此，我们分析了 HKT 对 POI 模型小鼠的影响，以确定 HKT 和 DKT 作用机制的相似性。
在对回肠远端进行肠道操作前后，将 HKT 口服给予每只小鼠。分析体内胃肠传输、白细胞浸润和炎症介质（如细胞因子和趋化因子）水平。
HKT 显著抑制中性粒细胞和巨噬细胞的浸润，并导致延迟的肠传输恢复。此外，它还显著降低诱导型一氧化氮合酶（iNOS）和厚朴酚的水平，表明具有抗炎活性。然而，它并没有抑制与 iNOS 诱导相关的白细胞介素（IL）-1β和 IL-6 水平的增加。相比之下，HKT 增加了神经生长因子（NGF）的水平，并抑制了与 iNOS 诱导相关的核因子-κB（NFκB）的水平，这表明存在神经元抗炎机制的可能性。
HKT 在 POI 小鼠模型中发挥了类似于 DKT 的缓解 POI 的作用，研究结果表明，它可能通过 NGF 发挥抗炎活性。
