A Discovery-Based Metabolomic Approach Using UPLC-Q-TOF-MS/MS Reveals Potential Antimalarial Compounds Present in Artemisia annua L.

In 1972, Nobel laureate Youyou Tu’s research team conducted clinical trials on the dried material ofArtemisia annuaL. from Beijing extracted by ether and then treated with alkali (called “ether neutral dry”), which showed that artemisinin was not the only antimalarial component contained. The biosynthesis of sesquiterpenoids inA. annuahas increased exponentially after unremitting cultivation efforts, and the plant resources are now quite different from those in the 1970s. In consideration of emerging artemisinin resistance, it is of great theoretical and practical value to further study the antimalarial activity ofA. annuaand explore its causes. The purpose of this study is to clarify scientific questions, such as “What ingredients are synergistic with artemisinin inA. annua?”, and “Are there non-artemisinin antimalarial ingredients inA. annua?”. In this paper, Beijing wildA. annuawas used as a control and two representative cultivation species ofA. annuawere selected to evaluate the antimalarial activity of the herbal medicine. The antimalarial activity of different extracts on mice was studied using the Peters’ four-day suppressive test. UPLC-Q-TOF-MS was used to obtain mass spectrum data for all samples, and a UNIFI platform was used for identification. A multivariate statistical method was used to screen the different compounds with positive correlations. The antimalarial activity of different components from the ether extract and alkali treatments was determined and antimalarial components other than artemisinin were obtained. A total of 24 flavonoids, 68 sesquiterpenoids and 21 other compounds were identified. Compounds associated with differential antimalarial activity were identified. The material basis for the antimalarial activity ofA. annuawas clarified. The antimalarial components ofA. annuainclude two categories: first, artemisinin and non-artemisinin antimalarial active components, of which the non-artemisinin antimalarial active components may include 5α-hydroperoxy-eudesma-4(15),11-diene; second, several antimalarial synergistic ingredients inA. annua, including arteanniun B, arteanniun B analogues and polymethoxy flavonoids.Keywords:Artemisia annuaL.;synergistic effect;antimalarial;UPLC-Q-TOF-MS;OPLS-DA