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Natural xanthones as modulators of the Nrf2/ARE signaling pathway and potential gastroprotective agents
Natalie Vivien Gunter1, Soek Sin Teh2, Ibrahim Jantan3
1School of Biosciences, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia.
Abstract:
Oxidative stress is implicated in the initiation, pathogenesis, and progression of various gastric inflammatory diseases (GID). The prevalence of these diseases remains a concern along with the increasing risks of adverse effects in current clinical interventions. Hence, new gastroprotective agents capable of inhibiting oxidative stress by modulating cellular defense systems such as the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway are critically needed to address these issues. A candidate to solve the present issue is xanthone, a natural compound that reportedly exerts gastroprotective effects via antioxidant, anti-inflammatory, and cytoprotective mechanisms. Moreover, xanthone derivatives were shown to modulate the Nrf2/ARE signaling pathway to counter oxidative stress in both in vitro and in vivo models. Thirteen natural xanthones have demonstrated the ability to modulate the Nrf2/ARE signaling pathway and have high potential as lead compounds for GID as indicated by their in vivo gastroprotective action-particularly mangiferin (2), α-mangostin (3), and γ-mangostin (4). Further studies on these compounds are recommended to validate the Nrf2 modulatory ability in relation to their gastroprotective action.
Insights
Natural compounds called xanthones show promise for treating gastric inflammatory diseases by reducing oxidative stress. They activate the Nrf2/ARE pathway, offering a safer alternative to current treatments.
Area of Science:
- Pharmacology
- Natural Products Chemistry
- Gastroenterology
Background:
- Oxidative stress is a key factor in gastric inflammatory diseases (GID).
- Current treatments for GID have limitations and potential adverse effects.
- There is a need for novel gastroprotective agents that target oxidative stress via cellular defense pathways.
Purpose of the Study:
- To explore xanthones as potential gastroprotective agents.
- To investigate the role of xanthones in modulating the Nrf2/ARE signaling pathway.
- To identify specific xanthone compounds with high potential for GID treatment.
Main Methods:
- Literature review of xanthone's effects on oxidative stress and GID.
- Analysis of studies on xanthone derivatives modulating the Nrf2/ARE pathway in vitro and in vivo.
- Identification of natural xanthones exhibiting gastroprotective actions.
Main Results:
- Thirteen natural xanthones were identified as modulators of the Nrf2/ARE signaling pathway.
- Mangiferin, α-mangostin, and γ-mangostin demonstrated significant in vivo gastroprotective effects.
- Xanthones exhibit antioxidant, anti-inflammatory, and cytoprotective properties relevant to GID.
Conclusions:
- Xanthones, particularly mangiferin, α-mangostin, and γ-mangostin, are promising candidates for GID treatment.
- Modulation of the Nrf2/ARE pathway is a key mechanism for xanthone's gastroprotective effects.
- Further research is recommended to validate these findings and develop new therapies.
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