Aged Black Garlic Exerts Anti-inflammatory Effects by Decreasing No and Proinflammatory Cytokine Production with Less Cytoxicity in LPS-stimulated Raw 264.7 Macrophages and LPS-induced Septicemia Mice

In this study, the anti-inflammatory and antisepticemic activities of a water extract of aged black garlic (AGE), which is not pungent, were compared with those of raw garlic extract (RGE). The methyl thiazolyl tetrazolium (MTT) assay showed that AGE was not toxic up to 1000 μg/mL and was at least four times less cytotoxic than RGE. AGE significantly suppressed the production of nitric oxide (NO), tumor-necrosis factor-α (TNF-α), and prostaglandin (PG)-E2 in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Furthermore, the inhibitory effect of AGE on LPS-induced inflammation was confirmed by downregulation of inducible NO synthase and TNF-α mRNA expression, as well as cyclooxygenase-2 protein expression. The anti-inflammatory activities of AGE were similar to those of RGE at nontoxic concentrations up to 250 μg/mL. Signal transduction pathway studies further indicated that both garlic extracts inhibited activation of mitogen-activated protein kinase and nuclear factor-κB induced by LPS stimulation. Treatment with both AGE and RGE in an in vivo experiment of LPS-induced endotoxemia significantly reduced the level of TNF-α and interleukin-6 in serum and completely protected against LPS-induced lethal shock in C57BL/6 mice. The results suggest that AGE is a more promising nutraceutical or medicinal agent to prevent or cure inflammation-related diseases for safety aspects compared with RGE.