title: Gastro-protective and Anti-stress Efficacies of Monomethyl Fumarate and a Fumaria indica Extract in Chronically Stressed Rats.
abstract: Results of the very first experiments conducted to evaluate therapeutic potentials of a fumarate containing Fumaria indica extract and of fairly low daily oral doses of monomethyl fumarate for prevention of chronic unavoidable foot-shock stress-induced gastric ulcers, and possible involvement of diverse neuro-hormonal and oxidative process in their stress response desensitizing effects are reported and discussed in this article. Preventive effects of 21 daily oral 60, 120, and 240 mg/kg doses of a standardized 50 % methanolic F. indica extract (MFI) and 1.25, 2.50, and 5.00 mg/kg/day of pure monomethyl fumarate (MMF) were compared in rats subjected to one hour daily unavoidable foot-shocks. A pharmaceutically well-standardized Withania somnifera (WS) root extract was used as a reference herbal anti-stress agent in all experiments. Effects of the treatments on stress-induced alterations in body weight, adrenal and spleen weights, gastric ulcer and ulcer index, weight of glandular stomach, protective mucosal glycoprotein content, cellular proliferation, oxidative stress on stomach fundus, and brain tissues of male rats were quantified. Other parameters quantified were plasma corticosterone levels, brain monoamine levels, and expressions of the cytokines TNF-α, IL-10, and IL-1β in blood and brain of stressed and treated rats. Most but not every observed stress-induced anomalies were suppressed or completely prevented by both MFI and pure MMF treatments in dose-dependent manner. Qualitatively, the observed activity profiles of both of them were similar to those of WS dose tested. These results reveal that both MFI and MMF are potent gastro-protective agents against chronic unavoidable stress-induced ulcers and strongly suggest that they act as regulators or modulators of monoamine, corticosterone, and cytokine homeostasis.
authors.affiliation: Neuropharmacology Research Laboratory, Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi, 221 005, India.
authors.forename: Anshul
authors.initials: A
authors.lastname: Shakya
authors.affiliation: Department of Molecular and Human Genetics, Faculty of Science, Banaras Hindu University, Varanasi, India.
authors.forename: Upendra Kumar
authors.initials: UK
authors.lastname: Soni
authors.affiliation: Department of Molecular and Human Genetics, Faculty of Science, Banaras Hindu University, Varanasi, India.
authors.forename: Geeta
authors.initials: G
authors.lastname: Rai
authors.affiliation: Stettiner Straße 1, Karlsruhe, Germany.
authors.forename: Shyam Sunder
authors.initials: SS
authors.lastname: Chatterjee
authors.affiliation: Neuropharmacology Research Laboratory, Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi, 221 005, India. vikas.phe@iitbhu.ac.in.
authors.forename: Vikas
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D005650:Fumarates / Q000494:pharmacology / Q000627:therapeutic use*; D031312:Fumaria / Q000737:chemistry*; D008297:Male; D008298:Maleates / Q000494:pharmacology / Q000627:therapeutic use*; D000432:Methanol / Q000737:chemistry; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D013270:Stomach / Q000187:drug effects / Q000473:pathology*; D013276:Stomach Ulcer / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D013315:Stress, Psychological / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
chemical_list: D016207:Cytokines; D005650:Fumarates; D008298:Maleates; D010936:Plant Extracts; D020011:Protective Agents; C073341:citraconic acid; D003345:Corticosterone; D000432:Methanol
keywords: Cytokine expression; Fumaria indica; Monoamines; Monomethyl fumarate; Stress; Ulcer