Biological Evaluation of Swintonia floribunda Leaf Extract Through Integrated GC‐MS, In Vivo , In Vitro , and In Silico Approaches Targeting Diarrhea, Pain, Fever, and Inflammation

Background Swintonia floribunda , a member of the Anacardiaceae family, is a traditional medicinal plant in Bangladesh. The present study aimed to identify potential therapeutic agents from Swintonia floribunda leaves. Accordingly, we evaluated the methanolic extract of Swintonia floribunda leaves (MESFL) for anti‐inflammatory, antinociceptive, antipyretic, and antidiarrheal activities using both in vitro and in vivo approaches. Methods The anti‐inflammatory effect of MESFL was determined using protein denaturation and membrane stabilization assays. Antinociceptive activity was assessed in mice using acetic acid–induced writhing, formalin‐induced paw‐licking tests, and hot plate and tail immersion methods. The yeast‐induced pyrexia model was used to evaluate antipyretic activity, while castor oil–induced gastrointestinal motility was assessed to evaluate antidiarrheal potential. GC‐MS analysis confirmed the presence of bioactive compounds. Molecular docking and ADMET studies were conducted to elucidate binding mechanisms, pharmacokinetics, and safety profiles. Results MESFL exhibited significant antipyretic activity in vivo and moderate antidiarrheal activity by reducing intestinal motility. Both acetic acid–induced writhing inhibition, suppression of paw licking, and increased latency period in both the hot plate and tail immersion methods confirmed its strong antinociceptive effect. Anti‐inflammatory activity was evident through inhibition of protein denaturation and protection against red blood cell lysis. GC‐MS and docking studies revealed several active phytoconstituents; among them, gamma‐tocopherol demonstrated the strongest binding affinities to COX‐2 (PDB Code: 1CX2) and 5‐lipoxygenase (PDB Code: 5Y3Z), while benzene derivatives showed interactions with heat shock protein 90α (PDB Code: 4U14) and voltage‐gated sodium channel Nav1.7 (PDB Code: 4YK5). ADMET analysis confirmed favorable pharmacokinetic and safety characteristics, supporting the drug‐likeness of the compounds. Conclusion MESFL exhibits notable anti‐inflammatory properties, along with significant antinociceptive and antipyretic activities and moderate antidiarrheal potential. These findings highlight its promise as a natural source of novel therapeutic agents.