<![CDATA[Background: Paracetamol, a first-line antipyretic, has limitations including a risk of hepatotoxicity at high doses and variations in effectiveness among products, making the exploration of natural antipyretic agents important. Orthosiphon aristatus leaves contain flavonoids, saponins, and tannins that may inhibit prostaglandin biosynthesis.Aims: This study aimed to evaluate the ability of an ethanolic extract of Orthosiphon aristatus leaves to reduce fever in male mice induced with 5% peptone.Methods: This laboratory experimental study used a completely randomized design involving 30 male white mice divided into five groups: negative control (0.5% Na-CMC), positive control (paracetamol 1.3 mg/20 g body weight), and ethanolic extract groups at doses of 100, 200, and 400 mg/kg body weight. Fever was induced by subcutaneous administration of 5% peptone. Rectal temperature was measured at baseline (Tbaseline), 1 hour after induction (T0), and at 30, 60, 90, 120, and 150 minutes after treatment (T30–T150).Data were analyzed using one-way ANOVA followed by the LSD post hoc test.Result: Phytochemical screening showed that the extract contained alkaloids, flavonoids, tannins, and saponins, with an extract yield of 11.02%. From 90 to 150 minutes, none of the three extract doses differed significantly from paracetamol (p > 0.05), whereas all differed highly significantly from the negative control (p < 0.001). The 100 mg/kg dose showed the fastest onset of action (41.07% at 30 minutes), while the 200 mg/kg dose produced the most stable effect. Conclusion: The ethanolic extract of Orthosiphon aristatus leaves exhibited antipyretic activity comparable to paracetamol. The 100 mg/kg body weight dose was identified as the lowest effective dose, showing the fastest onset of action and efficacy comparable to higher doses during the stable phase (T90–T150).]]>
