| Summary: | <i>Phyllanthus amarus</i> Schum. & Thonn. (Phyllanthaceae) is a medicinal plant that is commonly used to treat diseases such as asthma, diabetes, and anemia. This study aimed to examine the antiallergic activity of <i>P. amarus</i> extract and its compounds. The antiallergic activity was determined by measuring the concentration of allergy markers release from rat basophilic leukemia (RBL-2H3) cells with ketotifen fumarate as the positive control. As a result, <i>P. amarus</i> did not stabilize mast cell degranulation but exhibited antihistamine activity. The antihistamine activity was evaluated by conducting a competition radioligand binding assay on the histamine 1 receptor (H1R). Four compounds were identified from the high performance liquid chromatography (HPLC) analysis which were phyllanthin (<b>1</b>), hypophyllanthin (<b>2</b>), niranthin (<b>3</b>), and corilagin (<b>4</b>). To gain insights into the binding interactions of the most active compound hypophyllanthin (<b>2</b>), molecular docking was conducted and found that hypophyllanthin (<b>2</b>) exhibited favorable binding in the H1R binding site. In conclusion, <i>P. amarus</i> and hypophyllanthin (<b>2</b>) could potentially exhibit antiallergic activity by preventing the activation of the H1 receptor.
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