We report a pivotal role for IL-5 as an angiogenic activator. IL-5 increased proliferation, migration and colony tube formation in HUVECs associated with the phosphorylation of ERK and AKT/eNOS, and promoted microvessel sprouting from an angiogenesis animal model. The angiogenic effects were confirmed in IL-5-deficient mice and addition of IL-5 antibody. HSP70-1 was identified via expression profiling following IL-5 stimulation. A siRNA knockdown of HSP70-1 suppressed angiogenic responses and eNOS phosphorylation induced by IL-5. HSP70-1 overexpression enhanced IL-5-induced angiogenic responses. In addition, IL-5-induced neo-vascular formation was verified in both HSP70-1 knockout and HSP70-1 transgenic mice. Furthermore, transcription factor AP-1 was a main factor in IL-5-induced HSP70-1 in response to ERK and AKT signaling pathway. Angiogenic responses induced by VEGF had no effect in either HSP70-1 siRNA in vitro or HSP70-1 knockout mice. IL-5-induced angiogenic responses depended on the binding of IL-5Rα. Our data demonstrate that binding of IL-5 to IL-5Rα receptors enhances angiogenic responses by stimulating the expression of HSP70-1 via the eNOS signaling pathway.

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The present study was conducted to evaluate the anti-inflammatory and anti-arthritic effects of fermented Achyranthes japonica (Miq.) Nakai extract (FAJE). The FAJE was effective in nitrogen oxide (NO) scavenging in RAW264.7 cells. In the case of experimental Sprague Dawley (SD) rats injected with monosodium iodoacetate (MIA), the levels of TNF-α and IL-1β in blood increased in the osteoarthritis-induced group while decreasing in the group administered with FAJE. In addition, MMP-2 and MMP-9 in cartilage tissues increased in the osteoarthritis-induced group, but decreased in the group treated with FAJE. Cartilage examination indicated that the osteoarthritis-induced group exhibited cartilage erosion and cell degeneration, but in the FAJE administered group the tissue, conditions were recovered and cartilage proteoglycan was increased. Therefore, FAJE clearly showed anti-inflammatory effects and this suggests it is effective for recovery from osteoarthritis induced by MIA.

Inappropriate platelet aggregation can cause blood coagulation and thrombosis. In this study, the effect of an ethanol extract of Ramulus mori (ERM) on blood circulation was investigated. The antithrombotic activity of ERM on rat carotid arterial thrombosis was evaluated in vivo, and the effect of ERM on platelet aggregation and blood coagulation time was evaluated ex vivo. To evaluate the safety of ERM, its cytotoxicity to platelets and its effect on tail bleeding time were assessed; ERM was not toxic to rat platelets and did not prolong bleeding time. Moreover, administering ERM to rats had a significant preventive effect on carotid arterial thrombosis in vivo, and significantly inhibited adenosine diphosphate- and collagen-induced platelet aggregation ex vivo, whereas it did not prolong coagulation periods, such as prothrombin time and activated partial thromboplastin time. The results suggest that ERM is effective in improving blood circulation via antiplatelet activity rather than anticoagulation activity.

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