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Gastro-protective and Anti-stress Efficacies of Monomethyl Fumarate and a Fumaria indica Extract in Chronically Stressed Rats

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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.

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Acknowledgments

Authors would like to acknowledge generous support of Indian Herbs Research and Supply Co. Ltd., Saharanpur, India for providing the analytical characterized Fumaria indica extract, and Natural Remedies Pvt. Ltd., Bengaluru, India for providing complementary sample of standardized root extract of Withania somnifera along with its HPLC fingerprints. Anshul Shakya thankfully acknowledged the University Grants Commission, New Delhi, India for providing the financial assistance.

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  1. Neuropharmacology Research Laboratory, Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi, 221 005, India

    Anshul Shakya & Vikas Kumar

  2. Department of Molecular and Human Genetics, Faculty of Science, Banaras Hindu University, Varanasi, India

    Upendra Kumar Soni & Geeta Rai

  3. Stettiner Straße 1, Karlsruhe, Germany

    Shyam Sunder Chatterjee

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  1. Anshul Shakya
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Correspondence to Vikas Kumar.

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Shyam Sunder Chatterjee is a retired Head of Pharmacology Research Laboratories, Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany.

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Shakya, A., Soni, U.K., Rai, G. et al. Gastro-protective and Anti-stress Efficacies of Monomethyl Fumarate and a Fumaria indica Extract in Chronically Stressed Rats. Cell Mol Neurobiol 36, 621–635 (2016). https://doi.org/10.1007/s10571-015-0243-1

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