Mechanism And Application Of Menthol In The Relief Of Gastroesophageal Reflux

Gastroesophageal reflux disease（GERD）is a common gastrointestinal disease.During the disease,discomfort phenomena such as burning sensation in the stomach and acid swallowing are often present,which affects the patient’s quality of life to a certain extent.If not treated well and quickly,it will cause serious diseases such as esophagitis and esophageal cancer.Therefore,the development of special medical purpose food to relieve the discomfort and inflammation caused by gastroesophageal reflux makes important clinical significance.Transient receptor potential vanilloid 1（TRPV1）is a transient sensory potential channel.The activation of TRPV1 plays an important role in the inflammatory process and pain response.Some studies have found TRPV1 is involved in the nerve signal transmission process of"burning sensation"in esophageal nerve cells,which is related to the occurrence and development of gastroesophageal reflux disease.However,little research has been done in the role of TRPV1 in esophageal epithelial cells.We cannot ignore the fact that epithelial cells have important structural functions.It directly participates in the process of inflammation in response to acidic stimuli during reflux.In this study,we revealed the response mechanism of TRPV1 in esophageal epithelial cells and mice after acid stimulation.Furthermore,the purpose of this design is to seek a new therapeutic agent for gastroesophageal reflux disease from the perspective of TRPV1 inhibitors.The main research contents and results include the following two aspects:（1）The mechanism of TRPV1 involved in the pathological process of gastroesophageal reflux disease in esophageal epithelial cells.In vitro,HET-1A cells were stimulated by acidic medium to simulate the acidic microenvironment of the reflux process.We found that acidic stimulation caused an increase in the expression of TRPV1 in esophageal epithelial cells.Then,HET-1A cells were used for calcium imaging experiments.Transfection experiments confirmed that TRPV1 has a key role in disrupting calcium signaling homeostasis.The intensity of calcium influx will be enhanced by acid stimulation,which will cause disturbance of calcium signal in cells and the increase of inflammatory factors.The GERD mice model was established by acid perfusion solution,and then the mouse esophagus was isolated for biochemical and pathological analysis.After acid stimulation,TRPV1 expression was increased in the esophageal mucosal epithelium of mice,leading to inflammatory reactions and signs of epithelial hyperplasia and keratosis.（2）Verification process of the effects of targeted homologous molecules,specifically,that is analysis of the therapeutic effect of menthol on gastroesophageal reflux disease.In vitro,menthol was used to deal with acid-stimulated esophageal epithelial cells.After treatment,the expression of TRPV1 and inflammatory factors were reduced,and the intensity of Ca²⁺influx was weakened.The expression level of TRPV1 and pathological changes in the esophageal epithelium of mice were analyzed by immunohistochemical analysis and H&E staining.When reflux disease model mice were treated with menthol,the expression of TRPV1 was significantly reduced and epithelial hyperplasia symptoms of hyperkeratosis were significantly improved,and the inflammatory response was alleviated.In summary,TRPV1 is an important response element in the process of gastroesophageal reflux,which mediates the inflammatory response through calcium signaling pathways in esophageal epithelial cells.Menthol has a certain therapeutic effect on the inflammatory response of acid reflux,and it has the potential value to treat related diseases caused by gastroesophageal reflux.