The potential effects of globularifolin, an acylated iridoid glucoside, on cell survival, inflammation markers and free radicals scavenging were investigated. Viability assay on human myelomomonocytic cell line THP-1 and human peripheral blood mononuclear cells (PBMC) using the Cell-Titer Blue assay proved that globularifolin had no toxic effect at the tested concentrations. Conversely, it is proportional to the dose globularifolin increased growth of THP-1 cells (p <0.01). On human PBMC, globularifolin at 6.25 and 12.5 μM concentrations showed a stimulatory effect, while at 12.5-200 μM it suppressed response of PBMC to stimulation with phytohemagglutinin (PHA). Globularifolin (50-200 μM) enhanced neopterin formation dose-dependently, whereas tryptophan breakdown was not influenced. At 50-200 μM in unstimulated PBMC in THP-1 cells, globularifolin induced a significant expression of nuclear factor-κB (NF-κB) as was quantified by Quanti-Blue assay. By contrast, in lipopolysaccharide (LPS)-stimulated cells, the higher concentrations of globularifolin suppressed NF-κB expression dose-dependently and a significant decrease was observed at 200 μM concentration. A positive correlation was found between increased neopterin and NF-κB activity (p <0.01). Similarly, a positive correlation was observed between neopterin levels in mitogen-induced cells and NF-κB activity in LPS-stimulated cells after treatment with globularifolin (p=0.001). The free radical scavenging capacity of globularifolin evaluated by Oxygen Radical Absorbance Capacity (ORAC) assay showed relative ORAC values of 0.36±0.05 μmol Trolox equivalent/μmol. All together, results show that natural antioxidant globularifolin might represent a potential immunomodulatory as well as proliferative agent, which deserves further in vitro and in vivo studies.
Keywords: 2,2′-azobis(2-amidinopropane) dihydrochloride; 6-hydroxy- 2,5,7,8-tetramethyl-2-carboxylic acid; AAPH; Antioxidant activity; CTB; Cell-Titer Blue®; Cytotoxicity; FCS; FL; Globularifolin; HAT; IDO; IFN-γ; Immunomodulatory; Immunosuppressive; Iridoid glycoside; NF-κB; ORAC; PBMC; PHA; SEAP; TNF-α; Trolox; fetal calf serum; fluorescein; hydrogen atom transfer; indoleamine (2,3)-dioxygenase; interferon gamma; kyn; kynurenine; neop; neopterin; nuclear factor-κB; oxygen radical absorbance capacity; peripheral blood mononuclear cells; phytohemagglutinin; secreted embryonic alkaline phosphatase; trp; tryptophan; tumor necrosis factor alpha.
© 2013.