title: Mechanism(s) of action underlying the gastroprotective effect of ethyl acetate fraction obtained from the crude methanolic leaves extract of Muntingia calabura.
abstract: BACKGROUND
  Muntingia calabura L. (family Muntingiaceae), commonly known as Jamaican cherry or kerukup siam in Malaysia, is used traditionally to treat various ailments. The aim of this study is to elucidate the possible underlying gastroprotective mechanisms of ethyl acetate fraction (EAF) of Muntingia calabura methanolic leaves extract (MEMC).
  
  
  METHODS
  MEMC and its fractions were subjected to HPLC analysis to identify and quantify the presence of its phyto-constituents. The mechanism of gastroptotection of EAF was further investigated using pylorus ligation-induced gastric lesion rat model (100, 250, and 500 mg/kg). Macroscopic analysis of the stomach, evaluation of gastric content parameters such as volume, pH, free and total acidity, protein estimation, and quantification of mucus were carried out. The participation of nitric oxide (NO) and sulfhydryl (SH) compounds was evaluated and the superoxide dismutase (SOD), gluthathione (GSH), catalase (CAT), malondialdehyde (MDA), prostaglandin E2 (PGE2) and NO level in the ethanol induced stomach tissue homogenate was determined.
  
  
  RESULTS
  HPLC analysis confirmed the presence of quercetin and gallic acid in EAF. In pylorus-ligation model, EAF significantly (p <0.001) prevent gastric lesion formation. Volume of gastric content and total protein content reduced significantly (p < 0.01 and p < 0.05, respectively), while free and total acidity reduced in the doses of 250 and 500 mg/kg (p <0.001 and p <0.05, respectively). EAF also augmented the mucus content significantly (p < 0.001). Pre-treatment with N-nitro-L-arginine methyl ester (L-NAME) or N-ethylmaleimide (NEM) reversed the gastroprotective activity of EAF. EAF treatment markedly ameliorated the SOD, GSH and CAT activity and PGE2 and NO level while attenuating MDA level, relative to the vehicle group.
  
  
  CONCLUSIONS
  In conclusion, the underlying gastroprotective mechanisms of EAF could be associated with the antisecretory, participation of mucus, antiperoxidative, improvement of antioxidant status, modulation of NO and SH compounds, stimulation of PGE2 as well as presence of quercetin and gallic acid.
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia. dr_zaz@yahoo.com.|Integrative Pharmacogenomics Institute (iPROMISE), Level 7, FF3 Building, Universiti Teknologi MARA, 42300, Puncak Alam, Selangor, Malaysia. dr_zaz@yahoo.com.|Halal Product Research Institute, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. dr_zaz@yahoo.com.
authors.forename: Zainul Amiruddin
authors.initials: ZA
authors.lastname: Zakaria
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia. tavamani85@gmail.com.
authors.forename: Tavamani
authors.initials: T
authors.lastname: Balan
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia. madkucai89@gmail.com.
authors.forename: Ahmad Khusairi
authors.initials: AK
authors.lastname: Azemi
authors.affiliation: Phytochemistry Unit, Herbal Medicine Research Centre, Institute for Medical Research, Jalan Pahang, 50588, Kuala Lumpur, Malaysia. maizatul@imr.gov.my.
authors.forename: Maizatul Hasyima
authors.initials: MH
authors.lastname: Omar
authors.affiliation: Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia. norhafizahm@upm.edu.my.
authors.forename: Norhafizah
authors.initials: N
authors.lastname: Mohtarrudin
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia. zuraini@upm.edu.my.
authors.forename: Zuraini
authors.initials: Z
authors.lastname: Ahmad
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia. nazrulh@upm.edu.my.
authors.forename: Muhammad Nazrul Hakim
authors.initials: MN
authors.lastname: Abdullah
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia. mnasir@upm.edu.my.
authors.forename: Mohd Nasir Mohd
authors.initials: MN
authors.lastname: Desa
authors.affiliation: Integrative Pharmacogenomics Institute (iPROMISE), Level 7, FF3 Building, Universiti Teknologi MARA, 42300, Puncak Alam, Selangor, Malaysia. tehlaykek@yahoo.com.
authors.forename: Lay Kek
authors.initials: LK
authors.lastname: Teh
authors.affiliation: Integrative Pharmacogenomics Institute (iPROMISE), Level 7, FF3 Building, Universiti Teknologi MARA, 42300, Puncak Alam, Selangor, Malaysia. zakisalleh.mzs@gmail.com.
authors.forename: Mohd Zaki
authors.initials: MZ
authors.lastname: Salleh
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005707:Gallic Acid / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D019684:Magnoliopsida / Q000737:chemistry*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009093:Mucus / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves / Q000737:chemistry; D011794:Quercetin / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013276:Stomach Ulcer / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000897:Anti-Ulcer Agents; D000975:Antioxidants; D010936:Plant Extracts; D009569:Nitric Oxide; D008315:Malondialdehyde; D005707:Gallic Acid; D011794:Quercetin; D015232:Dinoprostone