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

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 iNOS induction, suggesting the possibility of a neuronal anti-inflammatory mechanism. CONCLUSIONS: 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.

Antinociceptive effect of N-acetyl glucosamine in a rat model of neuropathic pain.

OBJECTIVE: This study was aimed at evaluating the efficacy of glucosamine and potential mechanisms of actions in a neuropathic pain model in rats. METHODS: Glucosamine (500, 1000 and 2000 mg/kg) was administered via gavage route, 1 day before the chronic constriction injury (CCI) of sciatic nerve and daily for 14 days (prophylactic regimen), or from days 5 to 14 post-injury (therapeutic regimen), as the indicators of neuropathic pain, mechanical allodynia, cold allodynia and thermal hyperalgesia were assessed on days 0, 3, 5, 7, 10 and 14 after ligation. Inducible nitric oxide synthase (iNOS) and tumour necrosis factor alpha (TNF-α) gene expressions were measured by real-time polymerase chain reaction. TNF-α protein content was measured using the enzyme-linked immunosorbent assay method. RESULTS: Three days after nerve injury, the threshold of pain was declined among animals subjected to neuropathic pain. Mechanical and cold allodynia, as well as thermal hyperalgesia were attenuated by glucosamine (500, 1000, 2000 mg/kg) in the prophylactic regimen. However, existing pain was not decreased by this drug. Increased mRNA expression of iNOS and TNF-α was significantly reduced in the spinal cord of CCI animals by glucosamine (500, 1000, 2000 mg/kg) in the prophylactic regimen. The overall expression of spinal TNF-α was increased by CCI, but this increase was reduced in animals receiving glucosamine prophylactic treatment. CONCLUSION: Findings suggest that glucosamine as a safe supplement may be a useful candidate in preventing neuropathic pain following nerve injury. Antioxidant and anti-inflammatory effects may be at least in part responsible for the antinociceptive effects of this drug.

Inducible nitric oxide synthase involvement in the mechanism of action of Saccharomyces boulardii in castor oil-induced diarrhoea in rats.

The biotherapeutic agent Saccharomyces boulardii has been shown to inhibit castor oil-induced diarrhoea in rats in a dose-response fashion, and one of the suggested mechanisms of action included involvement of the nitric oxide pathway. The present study was designed to address this mechanism of action by firstly measuring the effects of S. boulardii on the inducible nitric oxide synthase (iNOS) isoform activity in vitro. Second, the effects of S. boulardii on the increase in colonic citrulline level associated with castor oil treatment were examined. In vitro, S. boulardii showed a dose-dependent inhibition of iNOS activity with an IC50 of 0.89 mg/ml. In the rat diarrhoea model, the antidiarrhoeal effect of S. boulardii was confirmed using a single oral dose of 12 x 10(10) CFU/kg (viable cells). In this model, castor oil significantly elevated citrulline level from 2526+/-164 to 3501+/-193 nmol/g in the colon. When the rats were treated with the same antidiarrhoeal single dose of S. boulardii, no increase in citrulline level was observed. Moreover, the iNOS inhibitor 1400 W at 10 mg/kg and the inhibitor of iNOS expression dexamethasone at 1 mg/kg, administered subcutaneously, blocked the citrulline production induced by the laxative. Taken together, these findings confirm the involvement of inhibition of the inducible isoform of nitric oxide synthase in the mechanism of action of S. boulardii in diarrhoea.