Different Forms of Manganese Provide Distinctive Metabolomics Signatures and Bioactive Profiles in Artemisia annua

Natural products are among the main ingredients of medicinal plants, and strategies that enhance their bioactive profile by elemental supplementation have emerged recently. Manganese is involved in various plant secondary metabolism pathways among different micronutrients.

This study investigated the effects of ionic (MnSO₄, MnCl₂), bulk (Mn₂O₃), and nano (Mn₂O₃-NP) manganese forms on Artemisia annua's secondary metabolism. It also studied the influence of the application method (seed priming vs. seed priming + foliar).

For this purpose, untargeted UHPLC-QTOF-HRMS metabolomics was conducted.

The findings revealed that Mn form and application method significantly influenced the metabolomic profile and secondary metabolite composition of the leaves and inflorescences, regardless of tissue type. Metabolomic profiling using untargeted analysis and multivariate statistical tools (PCA, PLS-DA, and VIP scoring) showed significant variation in bioactive compound accumulation. Mn₂O₃ and MnCl₂ were most effective in enhancing nitrogen-containing compounds, phenylpropanoids, flavonoids, and terpenoids, possibly via ROS-mediated biosynthesis. Mn₂O₃ strongly increased lignans, while Mn₂O₃-NP showed the highest artemisinin accumulation (3.2-3.7 mg g^-1 FW) compared to MnCl₂ and Mn₂O₃ (0.2-1.7 mg g^-1 FW). Key pharmacological metabolites such as vincristine, Momilactone A, and terbinafine were identified by VIP2 analysis.

Mn₂O₃-NP application through seed priming is a promising and cost-effective approach to modulate bioactive metabolite production in Artemisia annua.