Immunomodulatory and antiangiogenic mechanisms of polymolecular botanical drug extract C5OSEW5050ESA OS derived from Orthosiphon stamineus

Abstract

NuvastaticTM is a polymolecular botanical drug formulation containing a proprietary extract of a selected cultivar of Orthosiphon stamineus (OS) code name, C5OSEW5050ESA OS. The anti-angiogenic activity of C5OSEW5050ESA OS was explored by evaluating its activity towards a variety of angiogenesis modulators in vitro and in vivo. Multiplex immunoassays reveals that C5OSEW5050ESA OS inhibits Vascular Endothelial Growth factor (VEGF), Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), Interleukin 2 ( IL-2) & Interleukin 7 (IL-7), Nerve Growth Factor β (NGF-β) , Transforming Growth Factor -α (TGF-α) and Tumor Necrosis Factor- β (TNF-β). C5OSEW5050ESA OS also caused significant upregulation of interferon α (IFN-α), interferon β (IFN-β), interferon γ (IFN-γ) and Granulocyte-macrophage colony-stimulating factor (GM-CSF). C5OSEW5050ESA OS was found to inhibit endothelial cell proliferation and migration (92.6%) and disrupts the tube assembly (98.26%) for new blood vessel formation. The compound also inhibits neovascularisation in isolated rat aortic ring tissues (IC50 18.2 ± 2 µg/mL) and in chick chorioallantoic membrane assays (CAM) by 82.7%. In vivo matrigel plug assay treated with C5OSEW5050ESA OS shows inhibition of neovascularisation by 91.4± 3%. In conclusion, the study reveals that C5OSEW5050ESA OS has strong anti-angiogenic and immunomodulatory properties which may have significant clinical benefits in cancer therapy.