Combination of Patchouli Alcohol and Artemisinin Sodium for Antimalarial: Integrating Untargeted and Targeted LC–MS–Based Metabolomics

ABSTRACT Malaria, as a serious parasitic infectious disease, remains a major threat to global public security. This study investigated the metabolic mechanisms of patchouli alcohol (PA) and artemisinin sodium (SA) in treating malaria using pharmacodynamics and metabolomics. A Plasmodium berghei ANKA ( Pb A)–infected mouse model was established to evaluate the antimalarial effects of PA and SA combination therapy (SP). Pharmacodynamic results showed that the SP exhibited better therapeutic effects in infection suppression, weight recovery, and reduction of malaria pigment deposition compared with individual treatments. Untargeted metabolomics identified 146 plasma differential metabolites, including fatty acids, phospholipids, and inflammation‐related factors, linked to pathways such as unsaturated fatty acid biosynthesis and glycerophospholipid metabolism. Tetradecanedioic acid (TDA) was identified as a potential biomarker, reflecting the drug interactions and therapeutic efficacy. TDA was quantified by targeted metabolomics to study the interactions of combination drugs. The findings suggest that PA and SA synergistically enhance antimalarial effects by modulating lipid metabolism and anti–inflammatory properties and influencing membrane fluidity. This study provides insights into the metabolic mechanisms of PA and SA combination therapy, supporting its clinical application as a novel antimalarial adjuvant.