Another form of chronic gastritis in Japan is a symptomatic gastritis called functional dyspepsia (FD), and it is classified as a functional GI disorder (FGID). According to the Rome III criteria published in 2006 [
38], the diagnosis of FGIDs is based on the following conditions: patients exhibit symptoms originating from the GI tract without evident organic disease, and these bothersome symptoms persist even after various treatments, thus decreasing their quality of life (QOL) [
39]. FD has four representative symptoms, viz., epigastric pain, epigastric burning, postprandial fullness, or early satiety. It is common worldwide, and its prevalence has increased recently. The pathophysiology of FD is characterized by multifunctional disorders of the upper GI tract, e.g., disorders of GI motility [
40], abnormal acid secretion [
41], visceral hypersensitivity [
42],
H. pylori infection [
43], psychological factors [
44,
45], and imbalance of the autonomic nervous system (ANS) [
46]. Of these factors, most studies mainly focus on the disorders of GI motility, because they are closely related to the pathogenesis of FD. In general, gastric motility consists of three phases: reservoir, churning, and emptying. While previous reports have mainly focused on the delay in gastric emptying [
47], it is necessary to consider the total coordination of these phases for the better understanding of FD. Gastric accommodation, a reservoir function, originates from the proximal stomach and is important for the physiological function of the stomach. Neurological transmitters such as NO that are essential for this function have already been elucidated [
48,
49]. Impairment of gastric accommodation has also been reported to cause clinical symptoms such as epigastric discomfort, early satiety, and bloating of FD patients [
50]. Furthermore, we have previously reported that the impairment of reservoir function is associated with delay in gastric emptying, which results in dyspeptic symptoms [
40]. Thus, drugs that can improve the impairment of reservoir function of the stomach are desirable. With regard to traditional medicines, the kampo medicine rikkunshito regulates GI motility in a manner similar to prokinetic drugs. Hayakawa et al. [
9] reported that, in isolated guinea pig stomachs, rikkunshito promotes adaptive relaxation, which means gastric accommodation. Rikkunshito also induces the relaxation of gastric fundus smooth muscles isolated from diabetic neuropathic rats with gastric dysmotility [
51]. In addition, rikkunshito can improve gastric dysmotility mediated by NO or 5-HT3 receptor pathways [
10,
11]. Considering this basic evidence, rikkunshito may be a promising drug for the treatment of FD in the clinical field.
Unfortunately, an appropriate treatment regimen for FD has not yet been established, even though a variety of clinical trials considering the above pathogenesis have been conducted in Japan. Therefore, treatment may be empirically adopted for FD patients based on the predominantly suspected pathogenesis related to respective symptoms of FD. There is some evidence for the effectiveness of kampo medicines in the treatment of FD under such conditions. When FD was still called non-ulcer dyspepsia (NUD), Tatsuta et al. [
52] illustrated the efficacy of rikkunshito on gastric emptying in patients with NUD, which supports the data shown in the above basic studies. Interestingly, in addition to this effect on gastric motility, rikkunshito also improved GI symptoms in patients with NUD [
52]. To our knowledge, this is the first report in the English literature that describes rikkunshito as a promising drug for the improvement of symptoms of FD patients. Kusunoki et al. [
53] showed that rikkunshito may be beneficial for the treatment of FD patients with impaired gastric accommodation and gastric motility evaluated by the extracorporeal ultrasonography method. On the other hand, physical and psychological stress often causes gastric hypersensitivity to stimulation by mechanical balloon distension, which is generally well known as a pathogenesis of FD. Shiratori et al. [
54] showed that rikkunshito may improve stress-induced gastric hypersensitivity and/or changes in gastric wall tone by using gastric barostat method. One report assessed the efficacy of some herbal medicines under the condition of venipuncture stress. Rikkunshito and hangeshashinto but not hangekobokuto or ninjinto reversed the increase in plasma levels of neuropeptide Y, a representative neurotransmitter of the sympathetic nervous system of ANS, to the control levels [
55]. In addition, administration of rikkunshito decreases the afferent activity of the gastric vagal nerve, but increased the efferent activities of the gastric branches of the vagal nerve [
56]. From these findings with the fact that activity of sympathetic nervous system in the ANS of FD patient was relatively higher compared to that of the parasympathetic nervous system [
57], the above might be another pharmacological action of rikkunshito for the improvement of dyspeptic symptoms. According to another comparative human study, rikkunshito but not domperidone also improves symptoms of patients with FD in parallel with plasma ghrelin levels [
58]. Rikkunshito also has an impact on delayed gastric emptying in severely handicapped patients [
59] and on the coordination of the gastric myoelectric activity in post-operative dyspeptic children after GI surgery [
60]. These findings suggest that rikkunshito improves dyspeptic symptoms mediated by regulating gastric sensorimotor function or some inflammatory and/or neuroendocrinal mediators. Oikawa et al. also reported the efficacy of hangekoubokuto in FD patients. This efficacy is mediated by a reduction of gas volume in parallel with the improvement of symptoms of abdominal pain, indigestion, and constipation [
61]. Thus, there are some candidates among various Japanese traditional medicines for the treatment of both histological and symptomatic gastritis.