Orthosiphon stamineus Benth. (Orthosiphon grandiflorus Bold. or Clerodendranthus spicatus Thunb.) is an Indonesian medicinal herb traditionally used for diseases such as hypertension, diabetes, and kidney stones. Despite the importance of this last application, there are very few reports on it. Diuretic action is an important factor in kidney stone treatment, as an increase in the volume of fluid flowing through the kidney will help to dissolve the stones, assist their passing to avoid further retention, and flush out the deposits. Among the diverse roles of adenosine A₁ receptor antagonists in renal protection, many studies have shown that they can induce diuresis and sodium excretion. A bioassay-guided fractionation of a methanol-water extract of Orthosiphon stamineus leaves using the adenosine A₁ receptor binding assay resulted in the isolation of seven methoxy flavonoids as active ligands with K _i values in the micromolar range. The Hill slope values are not significantly different from unity (within 0.9 – 1.4), which indicates the antagonist effect to A₁-R. The results of this study thus provide a scientific foundation for the traditional use of Orthosiphon stamineus in kidney stone treatment, as the affinity of the active compounds isolated from it as adenosine A₁ receptor ligands allows them to be associated with diuretic activity, which is one possible treatment for renal lithiasis. CPA:N⁶-cyclopentyladenosine DPCPX:8-cyclopentyl-1,3-dipropylxanthine GFR:glomerular filtration rate RBF:renal blood flow