Unraveling the metabolic regulation of Eleutherococcus senticosus leaves by Penicillium oxalicum: insights from targeted and non-targeted metabolomics

The interaction between endophytic fungi and medicinal plants plays a crucial role in the production of secondary metabolites; however, the metabolic interplay between Eleutherococcus senticosus (E. senticosus) and Penicillium oxalicum (P. oxalicum) remains inadequately studied. This research employed both targeted and non-targeted metabolomics to elucidate the metabolic reprogramming induced by P. oxalicum in the leaves of E. senticosus. Targeted analysis utilizing UPLC-MS quantified five medicinal compounds, including syringin and oleanolic acid, along with 19 phenolic metabolites. Additionally, GC-MS-based non-targeted profiling identified 127 primary metabolites. The results demonstrated a distinct dose-dependent modulation pattern: optimal concentrations of P. oxalicum (low, CL; medium, CM) enhanced the biosynthesis of phenolic compounds, with significant accumulation of C6C1- and C6C3C6-type phenolics. In contrast, high concentrations (CH) suppressed the accumulation of most primary and secondary metabolites. Alterations in primary metabolism primarily involved carbohydrate and amino acid pathways, such as alanine, aspartate, and glutamate metabolism, indicating a reallocation of carbon and nitrogen from primary metabolism to defense-associated secondary metabolism under optimal elicitation conditions. Notably, eleutheroside E and most medicinal compounds reached maximum accumulation in CL-treated group, while isofraxidin peaked in CM-treated group. These findings elucidate the regulatory role of P. oxalicum in the metabolism of E. senticosus and underscore its potential to enhance the yields of bioactive compounds. This study establishes a scientific foundation for utilizing endophyte-plant interactions to optimize the cultivation of medicinal plants, balancing elicitation efficacy with metabolic equilibrium for sustainable phytopharmaceutical applications.