Chemico-biological interactions · 2025
Naringenin targets and inhibits Monoamine Oxidase A/B to bidirectionally regulate intestinal motility.
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Li Qi, Chen Yi, Zhang Yige, Xu Canwei, Tang Ting, Qian Yunzhi, Seng Ong Shun, Wang Yujuan, Fang Ling, Xu Tianshu
Аннотация
BACKGROUND: Monoamine oxidase (MAO), the principal enzymatic regulator of monoamine neurotransmitter catabolism, plays a critical role in modulating intestinal motility dynamics. In colonic tissues, MAO-A is predominantly expressed during monoamine degradation, whereas MAO-B exhibits a relatively lower expression level. This differential expression of MAO subtypes endows naringenin (NAR), a flavonoid compound that can competitively bind to the active sites of both MAO-A and MAO-B, with distinct dose-response thresholds for inhibiting these two enzyme isoforms. Consequently, this study aims to systematically elucidate the molecular mechanisms underlying NAR's regulation of intestinal motility through its selective inhibition of the two MAO subtypes, and to comprehensively analyze the associated dose-effect relationships. Ultimately, the research seeks to provide a theoretical basis for its dose optimization and the mitigation of toxicity and side effects.
METHODS: In this study, we constructed a slow-transmission constipation model in male C57BL/6 mice induced by loperamide (LOP), and systematically investigated the effects of NAR at different concentrations on intestinal motility, MAO activity and neurotransmitter metabolism.
RESULTS: This research showed that NAR at a dose of 25-300 mg/kg selectively targeted intestinal MAO-A, suppressing enzymatic activity and reducing 5-hydroxytryptamine (5-HT) catabolism. This accumulation of 5-HT enhanced intestinal motility. However, when the NAR concentration is ≥ 150 mg/kg, it can additionally cause MAO-B inhibition, which resulted in significant blockage of dopamine metabolism and caused an abnormal increase in dopamine content. Ultimately, it inhibited colonic peristalsis through the activation of the dopamine signaling pathway.
CONCLUSION: The results confirmed that NAR can regulate the activities of MAO-A/B in a threshold-dependent manner to achieve bidirectional regulation of intestinal motility.
METHODS: In this study, we constructed a slow-transmission constipation model in male C57BL/6 mice induced by loperamide (LOP), and systematically investigated the effects of NAR at different concentrations on intestinal motility, MAO activity and neurotransmitter metabolism.
RESULTS: This research showed that NAR at a dose of 25-300 mg/kg selectively targeted intestinal MAO-A, suppressing enzymatic activity and reducing 5-hydroxytryptamine (5-HT) catabolism. This accumulation of 5-HT enhanced intestinal motility. However, when the NAR concentration is ≥ 150 mg/kg, it can additionally cause MAO-B inhibition, which resulted in significant blockage of dopamine metabolism and caused an abnormal increase in dopamine content. Ultimately, it inhibited colonic peristalsis through the activation of the dopamine signaling pathway.
CONCLUSION: The results confirmed that NAR can regulate the activities of MAO-A/B in a threshold-dependent manner to achieve bidirectional regulation of intestinal motility.