Geraniol ameliorates TNBS-induced colitis: Involvement of Wnt/β-catenin, p38MAPK, NFκB, and PPARγ signaling pathways.

Abstract

AIMS:

Geraniol, a natural component of plant essential oils, exhibits potent chemopreventive effects in the colon; however, its possible role/mechanisms in experimental colitis have not been elucidated, which is the aim of this study.

MAIN METHODS:

To fulfill this goal, rats were treated for 11days with geraniol and/or sulfasalazine using a TNBS-induced colitis model.

KEY FINDINGS:

Geraniol significantly hindered the colitis-clinical signs (weight loss, colon edema,ulcerative area, colon/spleen mass indices) and opposed the altered oxidative/nitrosative stress. It restored the depleted total antioxidant capacity and lessened the elevated levels of nitric oxide and lipid peroxide. TNBS induced apoptosis and inflammatory cell infiltration, whereas geraniol curtailed these effects by diminishing the levels of caspase-3, intercellular adhesion molecule-1, and myeloperoxidase. The anti-inflammatory effect was documented by inhibiting the colon contents of prostaglandin E2 and interleukin-1β. In order to delve into the anti-colitic signaling pathways, geraniol inhibited the content/expression of glycogen synthase kinase (GSK)-3β, β-catenin, p38 mitogen activated protein kinase (p38MAPK), and nuclear factor kappa B (NFκB), but upregulated that of peroxisome proliferator activated receptor γ (PPARγ). These effects were comparable to those of sulfasalazine, the standard drug, whereas its combination with geraniol mediated effects that surpassed either treatment alone.

SIGNIFICANCE:

Geraniol in the current study improved experimental colitis partly via its antioxidant, anti-inflammatory, and immunosuppressive potentials, possibly by modulating the Wnt/GSK-3β/β-catenin, p38MAPK, NFκB, and PPARγ signaling pathways. The study also revealed that geraniol represents a valuable asset against colitis alone or in combination with the conventional anti-colitic therapies.

• Authors: Ayman A Soubh, Dalaal M Abdallah, Hanan S El-Abhar
• Journal: Life sciences (Life Sci) Vol. 136 Pg. 142-50 (Sep 01 2015) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 26165751 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Acyclic Monoterpenes
• Anti-Inflammatory Agents
• Antioxidants
• Immunosuppressive Agents
• NF-kappa B
• PPAR gamma
• Terpenes
• Trinitrobenzenesulfonic Acid
• geraniol

Topics

• Acyclic Monoterpenes
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Antioxidants (pharmacology, therapeutic use)
• Colitis (chemically induced, drug therapy, metabolism)
• Drug Evaluation, Preclinical
• Immunosuppressive Agents (pharmacology, therapeutic use)
• MAP Kinase Signaling System
• Male
• NF-kappa B (metabolism)
• PPAR gamma (metabolism)
• Rats, Wistar
• Terpenes (pharmacology, therapeutic use)
• Trinitrobenzenesulfonic Acid
• Wnt Signaling Pathway