J Neurogastroenterol Motil.  2022 Apr;28(2):255-264. 10.5056/jnm21204.

Yokukansan Suppresses Gastric Hypersensitivity and Eosinophil-associated Microinflammation in Rats With Functional Dyspepsia

• Duan S
• Imamura N
• Kondo T
• Kanda H
• Kogure Y
• Okugawa T
• Fukushima M
• Tomita T
• Oshima T
• Fukui H
• Noguchi K
• Dai Y
• Miwa H

• KMID: 2528040
• DOI: http://doi.org/10.5056/jnm21204

Abstract

Background/Aims
Herbal medicine is an important complementary therapy for functional dyspepsia (FD). However, its effect against gastric hypersensitivity in patients with FD has rarely been evaluated. Yokukansan (YKS), a traditional Japanese herbal medicine, is effective against neuropathic and inflammatory pain. This study aims to use a maternal separation (MS) stress-induced FD model to investigate the effects of YKS against gastric hypersensitivity, gastric motility, and duodenal micro-inflammation.
Methods
The MS stress model was established by separating newborn Sprague-Dawley rats from their mothers for 2 hours a day from postnatal days 1 to 10. At the age of 7-8 weeks, the rats were treated with YKS at a dose of 5 mL/kg (1 g/kg) for 7 consecutive days. After YKS treatment, electromyographic activity in the acromiotrapezius muscle by gastric distention and the gastric-emptying rate were assessed. Immunohistochemical analysis of eosinophils in the duodenum and phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 in the spinal cord was performed.
Results
YKS treatment suppressed MS stress-induced gastric hypersensitivity and decreased the elevated levels of p-ERK1/2 in the spinal cord. In the gastroduodenal tract, YKS inhibited eosinophil-associated micro-inflammation but did not improve gastric dysmotility.
Conclusions
YKS treatment improved gastric hypersensitivity by alleviating eosinophil-associated micro-inflammation in the gastroduodenal tract. This treatment may be considered an effective therapeutic option for epigastric pain and micro-inflammation in patients with FD.