Hangekobokuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus through its anti-inflammatory action

Abstract

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.Methods: 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.Results: 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

Intron retention as an excellent marker for diagnosing depression and for discovering new potential pathways for drug intervention

“…Characterisation of the IR genes restored by HKT (Figure 5C) showed that inflammation-related genes were the major restored IR genes (24 genes; 37.5%), with 7 mitochondria-related and 7 cilia-related genes each accounting for 10.9%. The anti-inflammatory effect shown here is consistent with the reported efficacy of many Japanese herbal medicines (31), including HKT (30). Interestingly, while HKT has been reported to have anti-inflammatory effects by reducing inducible nitric oxide synthase (iNOS), the IR of NOSIP (48), which has been reported as a modulator of NO, was consistently restored in the present study.…”

“…Japanese herbal medicines originated in ancient China and are widely used in Japan for a variety of conditions (31, 32). HKT (30) is one of the formulations and is taken for symptoms of mental anxiety, stagnant gas in the stomach and usually poor digestive function. In this study, HKT was used as a decoction in the following proportions, based on the formula of the Kitasato University Oriental Medicine Research Centre: Hange (Pinelliae Tuber) 6.0 g; Bukuryo (Hoelen) 5.0 g; Koboku (Magnoliae Cortex) 3.0 g, Shisoyo (Perillae Herba) 2.0 g; Syokyo (Zingiberis Rhizoma) 0.5 g.…”

“…We recruited subjects with depressive symptoms who had consented to participate in the "Study of Hangekobokuto (30) and the Intestinal Environment" conducted by the Kitasato University Oriental Medicine Research Center, and who scored between 6 and 20 on the Brief Depressive Symptom Scale (QIDS-J). After the benefits and risks of the study were explained to the subjects, written informed consent was obtained, and the following exclusion criteria were applied to those who consented.…”

A review of frequently used Kampo prescriptions: Part 2—Hangekobokuto

“…induction. In contrast, the increased IL-1β and IL-6 expressions associated with iNOS induction were not restored by HKT, and no increase in NGF expression was seen [60].…”

“…In addition, it decreased the production of inducible NOS (iNOS) and increased the expression of nerve growth factor (NGF) and decreased nuclear factor‐κB (NFκB), respectively, which are associated with iNOS induction. In contrast, the increased IL‐1β and IL‐6 expressions associated with iNOS induction were not restored by HKT, and no increase in NGF expression was seen [60].…”