title: Medicinal Plants for Management of Gastroesophageal Reflux Disease: A Review of Animal and Human Studies.
abstract: OBJECTIVE
  Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disease that causes troublesome symptoms and/or complications. The major therapeutic strategy for GERD focuses mainly on symptom alleviation using proton pump inhibitors (PPIs), which does not produce a perfect response in all patients. An approach with new therapeutic agents for GERD seems to be essential. The aim of this study was to review animal and human studies investigating the effect of medicinal plants in GERD as well as mechanisms underlying their therapeutic effects.
  
  
  METHODS
  Medline, Scopus, and Cochrane Central Register of Controlled Trials were searched for animal or human studies. The data collected covered January 1966-October 2015.
  
  
  RESULTS
  A total of 22 studies were included in this review, of which nine were animal studies and 13 were human studies. Ceratonia siliqua as a medicinal plant and rikkunshito as a multicomponent herbal preparation were the most frequently studied herbal medicines in GERD. Antioxidant and anti-inflammatory activities were the main mechanisms demonstrated in animal studies for ameliorating the effects of medicinal plants in GERD. Other mechanisms include downregulation of genes encoding inflammatory proteins, improvement of barrier function and gastric mucus, a decrease in gastric acid, and induction of tonic contractions of the lower esophageal sphincter. All herbal preparations used in human studies have led to the alleviation of symptoms related to GERD. Myrtus communis and Cydonia oblonga showed marked reduction in GERD symptoms comparable to omeprazole. The therapeutic effect of Cydonia oblonga persisted after discontinuation of the drug. Tongjlang and rikkunshito showed therapeutic effects for non-erosive reflux disease (NERD) where PPIs failed to show a promising effect. Studies on Ceratonia siliqua have been solely focused on regurgitation in infants, and a remarkable decrease in the number of regurgitations was demonstrated.
  
  
  CONCLUSIONS
  The multiple mechanisms of action of medicinal plants in GERD other than anti-secretory properties appear to provide more efficient treatment and helped to manage the histopathological changes associated with this disorder. Further studies are needed to understand the effects of medicinal plants on GERD better.
authors.affiliation: 1 Department of Traditional Medicine, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran .
authors.forename: Mehdi
authors.initials: M
authors.lastname: Salehi
authors.affiliation: 1 Department of Traditional Medicine, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran .
authors.forename: Hossein
authors.initials: H
authors.lastname: Karegar-Borzi
authors.affiliation: 1 Department of Traditional Medicine, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran .
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Karimi
authors.affiliation: 2 Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran .
authors.forename: Roja
authors.initials: R
authors.lastname: Rahimi
mesh_terms: D000818:Animals; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000627:therapeutic use*; D010946:Plants, Medicinal; D051381:Rats
chemical_list: D010936:Plant Extracts
keywords: gastroesophageal reflux disease; herbal medicine; non-erosive reflux disease