Aims; Accumulation of defense metabolites is an adaptive response to heavy metals in plants. However, deployment of multiple classes of defense metabolites under cadmium (Cd) and copper (Cu) toxicity is not understood. Here, the responses of parthenolide and phenylpropanoids were examined. Methods ;Quantification of parthenolide and phenylpropanoids, and the expression of parthenolide biosynthesis genes were performed in feverfew leaves. Photosynthetic and physiological analysis of feverfew seedling treated with Cd and Cu were used to confirm the relationship between concentration of heavy metals and secondary metabolites accumulation. In addition, we examined the role of trans-Cinnamic acid (CA) as a phenylalanine ammonia-lyase (PAL) inhibitor alone or together with different Cd and Cu concentrations on plant growth and metabolites accumulation. Results; Application of different Cu concentrations alone was more phytotoxic than respective Cd concentrations alone in terms of plant growth, photosynthesis, and oxidative status; however, addition of CA improved these attributes compared with their respective treatments alone. The results also revealed the repressing parthenolide biosynthesis versus phenylpropanoids when plants treated with heavy metals, whereas CA treatment showed the inverse effect. Conclusions; This study provides valuable information into the response of feverfew plants to Cd or Cu alone or together with a PAL inhibitor by linking stress-related physiological responses to changes in metabolites
