Production of xanthones with antimicrobial and antioxidant activities by Hypericum perforatum L. cells

Hypericum perforatum L. (HP) is a well-known medicinal plant, widely used across the world. Previously we found that elicitation of HP cell cultures induces high accumulation of xanthones [1]. Xanthones are excellent antioxidants, which can act as metal chelators, free radical scavengers and inhibitors of lipid peroxidation [2]. Several pharmacological properties of xanthones such as hepatoprotective, anti-inflammatory, cancer chemopreventive and anticancer activities can be explained in part by their antioxidant properties. Other activities of xanthones such as antimycobacterial, antiparasitic, antiretroviral and antimalarial can be attributed to their antimicrobial properties [2].

We studied the potential of HP cells to produce xanthones with pharmacological activities when induced by a biotic stress: elicitation with Agrobacterium tumefaciens. Elicited HP cells showed the accumulation of xanthones in high concentration, up to 4mg/g cells (dry wt), within 24h. Those values were 12 times higher than observed on control samples. Subsequently, A. tumefaciens viability started to decline and reached the level of complete mortality within 12h while the HP cells remained viable. Additionally, the methanolic extract from elicited cells showed 10 times higher antimicrobial and increased antiradical activities than the extract from non-elicited cells. The phenolic profile of the elicited HP cells showed the production of several new xanthones. Some major xanthones were isolated and fully identified. Antioxidant (DPPH reduction and inhibition of lipid peroxidation) and antimicrobial (colony forming units and growth inhibition zone) activity assays with isolated compounds revealed that the xanthones accumulated after elicitation plays two significant roles: i- acting as phytoalexins/phytoanticipins having anti-bacterial activity against A. tumefaciens; ii- acting as antioxidants, probably protecting the plant cells from oxidative damage (an intense oxidative burst is observed during the elicitation procedure).

Acknowledgments: This work is supported by an FCT grant (POCTI/AGR/40283/2001). G. Franklin is supported by an FCT postdoctoral fellowship (SFRH/BPD/17102/2004). L. Conceição is supported by an FCT PhD fellowship (SFRH/BD/13318/2003).

References: [1] Conceição, L. et al. (2006) Phytochemistry 67: 149–155. [2] Pinto, M. et al. (2005) Curr. Med. Chem. 12: 2517–2538.