In vivo, in vitro, and in silico evaluation of the analgesic, antidiarrheal, and anthelmintic activities of methanolic extract of Syzygium grande (Wight) Walp

• MESG shows promise as a potential source of natural analgesic, antidiarrheal, and anthelmintic agents. • In silico study indicated that Gamma-Sitosterol was among the top compounds from MESG, showing high binding affinity to target receptors. • MESG compounds showed activity among in vitro & in vivo tests. Syzygium grande (syn. Eugenia grandis), commonly known as the sea apple, is a medicinally important plant that has been traditionally used to treat various ailments, including coughs, hemorrhoids (piles), dental problems, dysentery, bronchitis, and diabetes. This study aimed to evaluate the in vitro anthelmintic, in vivo analgesic, and antidiarrheal activities of the methanolic extract of S. grande (MESG) using Swiss albino mice. The anthelmintic activity was tested on the earthworm Pheretima posthuma . At the same time, analgesic effects were assessed using three models: the acetic acid-induced writhing test, the formalin-induced paw licking test, and the hot plate test. Antidiarrheal activity was evaluated using castor oil-induced diarrhea and the gastrointestinal motility test with charcoal meal. To support experimental findings, in silico methods such as molecular docking, ADME/T, PASS prediction, and network pharmacology were employed. Significant writhing inhibition was shown by MESG at 400 mg/kg—66.82% in the acetic acid test and 63.38% in the formalin test (p < 0.001), and showed marked analgesic activity in the hot plate test. At 200 mg/kg, the extract also exhibited strong antidiarrheal effects (p < 0.001). In the anthelmintic test, MESG at 10 μg/mL showed maximum efficacy comparable to levamisole (10 μg/mL). To clarify the multi-target potential of S. grande phytochemicals in modifying key proteins involved in pharmacological processes, this study combines network pharmacology with molecular docking. Molecular docking results revealed that gamma-sitosterol exhibited the highest binding affinity against 6COX, 5ZHP, and 1SA0 protein targets, suggesting strong potential as a drug candidate due to its favorable interactions. Based on both experimental and computational evidence, MESG shows promise as a potential source of natural analgesic, antidiarrheal, and anthelmintic agents, warranting further research for drug development.