title: Novel sequential stress model for functional dyspepsia: Efficacy of the herbal preparation STW5.
abstract: BACKGROUND
  Many screening procedures for agents with potential usefulness in functional dyspepsia (FD) rely on animals exposed to stress early in life (neonatal maternal separation, NMS) or in adulthood (restraint stress, RS).
  
  
  OBJECTIVE
  Since many clinical cases of FD have been associated with stress in early life followed by stress in adulthood, a sequential model simulating the clinical situation is described. To explore the validity of the model, the efficacy of STW5, a multicomponent herbal preparation of proven usefulness in FD, was tested.
  
  
  METHODS
  A sequential stress model established where rats are exposed to NMS after birth followed later by RS in adulthood. Stress hormones and ghrelin were measured in plasma, while responsiveness of stomach fundus strips to smooth muscle stimulants and relaxants was assessed ex-vivo. The effectiveness of treatment with STW5 a few days before and during exposure to RS in preventing changes induced by the stress model is reported and compared to its efficacy when used in animals subjected to RS alone.
  
  
  RESULTS
  Responses to both stimulants and relaxants were reduced to various extents in the studied models, but treatment with STW5 tended to normalize gastric responsiveness. Plasma levels of ghrelin, corticosterone releasing factor, and corticosterone were raised by RS as well as the sequential model. Treatment with STW5 tended to prevent the deranged parameters.
  
  
  CONCLUSIONS
  The sequential stress model has a place in drug screening for potential usefulness in FD as it simulates more the clinical setting. Furthermore, the findings shed more light on the mechanisms of action of STW5 in FD.
authors.affiliation: Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany; Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany. Electronic address: heba.abdelaziz@gmail.com.
authors.forename: Heba
authors.initials: H
authors.lastname: Abdel-Aziz
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Walaa
authors.initials: W
authors.lastname: Wadie
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Hala F
authors.initials: HF
authors.lastname: Zaki
authors.affiliation: Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Müller
authors.affiliation: Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Kelber
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Mohamed T
authors.initials: MT
authors.lastname: Khayyal
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D004195:Disease Models, Animal; D004415:Dyspepsia / Q000188:drug therapy*; D005260:Female; D005769:Gastrointestinal Motility; D054439:Ghrelin / Q000097:blood; D008297:Male; D008426:Maternal Deprivation; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013315:Stress, Psychological
chemical_list: D054439:Ghrelin; D010936:Plant Extracts; C039964:iberogast; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
keywords: Functional dyspepsia; Gastric accommodation; Ghrelin; Neonatal maternal separation; Restraint stress; STW5