Hyperforin is a potent inhibitor of inflammation-triggered angiogenesis

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Hyperforin (Hyp) is the major lipophilic anti-depressant compound of St. John’s wort (Hypericum perforatum), here we investigated its potential anti-inflammatory and anti-angiogenic properties as a stable salt (Hyp-DHCA) in vitro and in vivo. Hyperforin was able to control in a dose-dependent manner the chemotaxis of polymorphonuclear (PNM) leukocytes, with no collateral effects on their viability. In particular, non-cytotoxic micromolar concentration of hyperforin restrained in vitro the capacity of PMNs and monocytes to migrate towards relevant chemotactic stimuli such as interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1, CCL2), respectively. The anti-angiogenic properties of Hyperforin was confirmed in vitro in the Matrigel morphogenesis assay, where it limited the formation of capillary-like structures. Moreover, in the in vivo matrigel-sponge model assay Hyperforin exhibited anti-inflammatory and anti-angiogenic activities. The evaluation of haemoglobin content in matrigel pellets as an indicator of angiogenesis shows a strong anti-angiogenic activity of Hyperforin, both mixed in the matrigel solution at the same concentration used in vitro or when injected i.p. (1mM) twice a day, with a pre-treatment starting two days before matrigel injection. Micromolar Hyperforin was strongly effective in inhibiting chemokine-triggered angiogenesis in a dose dependent manner. Furthermore, in the highly angiogenic Kaposi’s sarcoma xenograft model Hyperforin inhibited tumor growth and vascularization.
 >We demonstrate that Hyperforin is a potent inhibitor of inflammation-triggered angiogenesis induced by chemokines of tumor angiogenesis.