Browsing by Author "Yibcharoenporn C."

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    AMPK in Intestinal Health and Disease: A Multifaceted Therapeutic Target for Metabolic and Inflammatory Disorders
    (2025-01-01) Yibcharoenporn C.; Muanprasat C.; Moonwiriyakit A.; Satitsri S.; Pathomthongtaweechai N.; Yibcharoenporn C.; Mahidol University
    The intestines play essential roles in nutrient absorption and immune function and help maintain a protective barrier. Disruptions to its function can result in various diseases, including metabolic disorders, inflammation, and cancer. As a key regulator of cellular energy levels, 5’-adenosine monophosphate-activated protein kinase (AMPK) is essential for intestinal health. Beyond its established metabolic role, emerging evidence suggests that AMPK exerts profound effects on intestinal cell physiology, influencing cell proliferation and differentiation, inflammation, autophagy, barrier integrity, and smooth muscle contractility. Here, we explore the structure and regulation of AMPK, as well as its diverse roles in intestinal diseases and potential as a therapeutic target. Our findings reveal that AMPK is a multifaceted regulator of intestinal health, modulating various cellular processes and intestinal diseases. It plays a dual role in cancer, acting as both a tumor suppressor and promoter, and it regulates inflammatory pathways, autophagy, tight junction formation, and smooth muscle contractility. Both natural and synthetic AMPK activators offer promise as therapeutic agents. This review of AMPK’s mechanisms and activators offers valuable insights for developing novel therapies for intestinal disorders. Further research is needed to fully define AMPK’s roles and therapeutic potential.
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    Inhibition of CFTR-mediated intestinal chloride secretion by nornidulin: Cellular mechanisms and anti-secretory efficacy in human intestinal epithelial cells and human colonoids
    (2024-12-01) Yibcharoenporn C.; Kongkaew T.; Worakajit N.; Khumjiang R.; Saetang P.; Satitsri S.; Rukachaisirikul V.; Muanprasat C.; Yibcharoenporn C.; Mahidol University
    Secretory diarrhea, a major global health concern, particularly among young children, is often characterized by excessive chloride secretion through the cystic fibrosis transmembrane conductance regulator (CFTR) channel. Nornidulin, a fungus-derived natural product from Aspergillus unguis, has previously been shown to inhibit cAMP-induced Cl- secretion in T84 cells (human intestinal cell lines). However, the cellular mechanism of nornidulin in inhibiting cAMP-induced Cl- secretion and its anti-secretory efficacy is still unknown especially in a human colonoid model, a preclinical model recapitulating intestinal physiology in humans. This research study aimed to examine the mechanism of nornidulin to inhibit cAMP-induced chloride secretion and assess its ability to reduce fluid secretion in both T84 cells and human colonoid models. Apical Cl- current analyses showed that nornidulin inhibited CFTR-mediated Cl- current in T84 cells with IC50 of ~1.5 μM. Nornidulin treatment had no effect on CFTR protein expression. Additionally, the inhibitory effects of nornidulin on CFTR-mediated chloride currents were unaffected by the presence of compounds that inhibit negative regulators of CFTR function, such as protein phosphatases, AMP-activated protein kinases, and phosphodiesterases. Interestingly, nornidulin suppressed the increase in intracellular cAMP levels caused by forskolin, an activator of adenylate cyclases, in T84 cells. Using human colonoid models, we found that nornidulin significantly suppressed the forskolin and cholera toxin-induced fluid secretion, indicating that nornidulin exerted an antisecretory effect in human intestinal epithelia. Collectively, nornidulin represents a novel class of fungus-derived inhibitors of CFTR-mediated Cl- secretion, potentially making it a promising candidate for the development of anti-secretory treatments.