Xiangsha Liujunzi Decoction Alleviates Symptoms in Rats With Functional Dyspepsia Through EGC-Derived NGF

Abstract Background: Xiangsha Liujunzi (XSLJZ) decoction is a traditional chinese prescription that shows to be effective in functional dyspepsia (FD). However, the underlying mechanism remains to be elucidated. Nerve growth factor (NGF) secreted from enteric glial cells (EGCs) is associated with visceral hypersensitivity (VH), which has been wildly accepted as the main pathological mechanism of FD. But it is not clear whether and how EGC-derived NGF contributes to VH in FD. The present study aimed to evaluate the effects of XSLJZ decoction on FD and investigate whether XSLJZ decoction relieves VH by inhibiting EGC-derived NGF and TrkA-Akt-TRPV1 axis.Methods: FD rat models were established using iodoacetamide and modified multiple platform method. The validation of FD model and effects of XSLJZD decoction on FD were evaluated in terms of weight, food intake, hematoxylin-eosin staining and Von Frey test. The expression levels of glial fibrillary acidic protein (GFAP), NGF and transient receptor potential vanilloid receptor 1 (TRPV1) were detected by immunohistochemistry and western blot analysis. The expression of TrkA and Akt was determined by western blot analysis. The co-localization of GFAP and NGF was observed by double-label immunofluorescence.Results: XSLJZ decoction increased the weight, food intake and pain threshold of FD rats. The expression levels of GFAP and NGF, together with NGF-positive EGCs were increased in FD rats, but decreased following XSLJZ decoction treatment. Furthermore, XSLJZ decoction downregulated the over-expression of TrkA, Akt and TRPV1 in FD rats.Conclusions: XSLJZ decoction can effectively improve the symptoms of FD and alleviate VH in FD, which may be mediated via EGC-derived NGF and TrkA-Akt-TRPV1 axis.