Exploring the Analgesic and Antidiarrheal Properties of Angelicin Through Cyclooxygenase Inhibition and Μ‐Opioid Receptor Interaction: In Vivo and In Silico Studies

Angelicin (AGN), an angular furocoumarin, exhibits notable anti-inflammatory and biological activities. However, its potential for managing pain and diarrhea, and the underlying mechanisms, remain poorly explored. This study aimed to investigate the analgesic and antidiarrheal properties of AGN and elucidate its possible mechanisms of action through in vivo and in silico approaches. Mice received AGN (2.5, 5, and 10 mg/kg, i.p), DFS (25 mg/kg, p.o), LOP (3 mg/kg p.o), and BSS (10 mg/kg, p.o), after 30 min of administration, for an analgesic test; 0.7% acetic acid at 10 mL/kg (i.p) induced writhing, observed latency, and number of writhing. Antidiarrheal activity was assessed by using castor oil (0.5 mL, p.o) induced diarrhea in mice, observing latency and number of diarrhea secretions over 3 h. Additionally, Molecular docking studies were performed to analyze AGN's interactions with cyclooxygenase (COX-1/2) enzymes and the µ-opioid receptor (MOR). Drug-likeness and toxicity profiles were predicted using SwissADME and ProTox-III. AGN demonstrated significant, dose-dependent analgesic and antidiarrheal effects. Its combination with standard drugs (DFS, LOP, BSS) showed enhanced efficacy. Molecular docking revealed strong binding affinities of AGN for COX-1 (-7.4 kcal/mol), COX-2 (-8.0 kcal/mol), and MOR (-7.1 kcal/mol). Pharmacokinetic predictions indicated good drug-likeness, and toxicity profiling suggested a favorable safety margin. These results strongly suggest that AGN is a promising dual-action therapeutic candidate for pain and diarrhea, likely mediated through COX inhibition and MOR interaction. Further studies are warranted to validate these mechanisms and develop optimized AGN-based formulations for clinical translation.