Hewei Jiangni granule alleviates visceral hypersensitivity of non-erosive reflux diseasestromal interaction molecule 1/transient receptor potential vanilloid subfamily member 1 pathway.

Abstract

Objective: To explore if Hewei Jiangni granule (, HWJNG) could regulate esophageal hypersensitivity via stromal interaction molecule 1 (STIM1)/transient receptor potential vanilloid subfamily member 1 (TRPV1) pathway.

Methods: Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography. In vivo, animal model of non-erosive reflux disease (NERD) was established by fructose intake and restraint stress. HWJNG and Omeprazole were administered by gavage to the drug intervention group. Reflux and visceral hypersensitivity were analyzed by pathological changes, PH value test, mechanical paw withdrawal threshold, thermal withdrawal latency and mast cells (MCs) degranulation. In vitro, substance P (SP)-induced P815 cells and dorsal root ganglion (DRG) cells were co-cultured. Expression in both mice and cells of STIM1, TRPV1, and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Moreover, overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.

Results: HWJNG significantly suppressed intercellular space widening, injury of mitochondrial, MCs degranulation, mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice. HWJNG inhibited expression of visceral hypersensitivity-related gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells, and expression of the STIM1, TRPV1 and related neurotransmitters in DRG and DRG cells. STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca²⁺ flow into the cytoplasmic space of DRG cells. Furthermore, HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.

Conclusion: HWJNG suppressed intercellular space widening in NERD mice, stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity viaSTIM1/TRPV1 pathway.