β-Sitosterol Mediates Gastrointestinal Smooth Muscle Relaxation Induced by <i>Coccoloba uvifera</i> via Muscarinic Acetylcholine Receptor Subtype 3

• Published in: Scientia Pharmaceutica
• Main Authors: Francisco J. Aguirre-Crespo, José L. Aragón-Gastélum, Eduardo J. Gutiérrez-Alcántara, Pedro Zamora-Crescencio, Diana L. Gómez-Galicia, Diego R. Alatriste-Kurzel, Guzman Alvarez, Emanuel Hernández-Núñez
• Format: Article
• Language: English
• Published: MDPI AG 2024-04-01
• Subjects: <i>C. uvifera</i>; aqueous extracts; β-sitosterol; spasmolytics agent
• Online Access: https://www.mdpi.com/2218-0532/92/2/19
• ISSN: 0036-8709; 2218-0532

<i>Coccoloba uvifera</i> is a Mayan medicinal plant, and these leaves are used as antidiarrheal and diuretic agents. In the present work, we develop in-vitro, ex-vivo, in-vivo, and in-silico strategies to evaluate several aqueous extracts of <i>C. uvifera</i> leaves. In vitro tests showed that decoction extract (CuDe) presented the best yield and chlorophyll, phenol, and flavonoid content; however, CuDe showed low antioxidant activity (DPPH model). All aqueous extracts exert spasmolytic and vasorelaxant activity in a concentration-dependent manner (ex vivo), and in vivo tests showed that CuDe exerts the best antiperistaltic and diuretic effects. The in-silico analysis suggests that <i>C. uvifera</i> triterpenes act as a ligand of GPCR, and β-sitosterol could act as an antagonist of muscarinic acetylcholine receptor subtype 3 (m3AChR). In the context of aqueous extracts of <i>C. uvifera</i>, β-sitosterol and their heterosides were identified by FTIR and ¹H-NMR spectroscopy. The concerted binding of β-sitosterol and other triterpenes within the m3AChR binding site may be relevant for the induction of relaxant effects at the gastrointestinal smooth muscle level. In this context, <i>C. uvifera</i> is a high-value plant species that requires analytical and pharmacological studies to confirm traditional medicinal use.