Abstract
Anxiety and depression often occur with gastrointestinal symptoms. Although the Japanese traditional medicine (Kampo medicine) bukuryoingohangekobokuto (BGH) is approved for treating anxiety, neurotic gastritis, and heartburn, its effect on gastrointestinal motility remains poorly known. This study aimed to examine the effect of BGH on delayed gastric emptying in stress model mice and clarified its action mechanism. Seven-week-old C57BL/6 male mice were acclimated for a week and fasted overnight. Stress hormone, corticotropin-releasing factor (CRF), was intracerebroventricularly injected to mice, and solid nutrient meal (ground chow and distilled water) was orally administered 1 hour after. Gastric contents were collected to evaluate gastric emptying rates by measuring its dry weight. Injection of CRF (0.3 or 1.0 μg/mouse) significantly delayed the 2-hour gastric emptying in mice. BGH (1.0 g/kg), which was administered 30 minutes before the CRF injection, significantly ameliorated the delayed gastric emptying induced by CRF (0.3 μg/mouse). BGH (0.5, 1.0 g/kg) significantly enhanced the 1-hour gastric emptying and slightly increased the 2-hour gastric emptying in mice without CRF injection. In vitro functional assays showed that components of BGH antagonized or inhibited CRF type-2, dopamine D2/D3, neuropeptide Y Y2 receptors, or acetylcholinesterase. In conclusion, the components of BGH may exert synergistic effects on improving gastric emptying via various targets. BGH is considered to be potentially useful for treating gastrointestinal dysmotility with psychological symptoms.
Highlights
Patients rarely describe their psychiatric symptoms when their major complaints include gastrointestinal disorders, psychological symptoms such as anxiety and depression may possibly lie behind gastrointestinal symptoms
Evaluation of the antagonistic activities against human CRF2 receptor transfected in HEK-293 cells was performed by measuring the effects of the test compounds on cAMP production induced by 100 nM human corticotropin-releasing factor (CRF) incubated for 30 minutes at room temperature via the HTRF detection method (Catalog No 2086)
Evaluation of the antagonistic activities against human dopamine D2, D3, and neuropeptide Y (NPY) Y2 receptors expressed in CHO-K1 cells, CHO-K1, and KAN-TS cells, respectively, was performed by preincubation of the test compounds and/or vehicle with the membrane proteins (0.1, 0.04, 0.04 mg/ml, respectively) and GDP (10, 1, 0.001 mM) in 20 mM HEPES, pH 7.4, 100 mM NaCl, 10 mM MgCl2, 1 mM DTT, and 1 mM EDTA for 20 minutes at 25°C, and SPA beads are added for another 60 minutes at 30°C. e reaction was initiated by 0.3 nM [35S]GTPcS for an additional incubation period (15, 30, 30 minute)
Summary
Patients rarely describe their psychiatric symptoms when their major complaints include gastrointestinal disorders, psychological symptoms such as anxiety and depression may possibly lie behind gastrointestinal symptoms. Psychosocial disturbance is highly prevalent in patients with functional gastrointestinal disorder [1,2,3,4]. Elderly people who likely experience depression and gastrointestinal diseases are at the risk of facing a high total symptom burden [5], leading to a poor quality of life [6] and increased use of health services [7, 8]. Almost 90% of physicians in Japan use Kampo medicines in daily practice under the approval of the Japanese Ministry of Health, Labour and Welfare. Multicomponent characteristics, a Kampo medicine may have the potential to deal with multiple symptoms. Us, they are expected to solve the problem of polypharmacy, which is a well-known risk for adverse drug reactions in the elderly patients [9].
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