Chaihu-Shugan-San, a traditional Chinese medicine formula, treats functional dyspepsia by inhibiting central sensitization-related activity and modulating glutamate metabolism via NMDAR/CaMKII signaling pathway.
The methodology of this study involved creating a functional dyspepsia rat model through tail-clamp stimulation and gavage, which was then treated with Chaihu-Shugan-San decoction over a four-week period. Various functions and measurements were then assessed; these included anxiety-like behaviours through an open-field test, the gastric emptying rate to evaluate gastrointestinal motility function, and the expression of c-fos in the spinal cord to reflect visceral hypersensitivity. Microstructural integrity of nerve cells, synaptic clefts, and synaptic vesicles were analyzed using transmission electron microscopy, and pathological changes in gastric tissue were clarified with Hematoxylin and eosin staining.
The discussion of results revealed that the treatment increased gastric motility and alleviated central sensitization, with rodents showing lower gastric motility and strong activation of c-fos initially. The treatment was found to affect several metabolisms, as discovered through fecal and serum metabolomics. After the treatment, the decrease of Iba1 and NOX2 in the amygdala compared to untreated rodents indicated an inhibition of central sensitization. There was also an increase in the levels of postsynaptic density protein 95, EAAT2 and VGLUT1 in the amygdala and spinal cord, and a decrease in the protein levels of Calcium-calmodulin-dependent protein kinase II, N-methyl-d-aspartate receptors, and Interleukin-1β in the spinal cord. This showed that the treatment significantly modulated the glutamate metabolic pathway.
