Ji Hyeon Ryu

Short-term heating reduces the anti-inflammatory effects of fresh raw garlic extracts on the LPS-induced production of NO and pro-inflammatory cytokines by downregulating allicin activity in RAW 264.7 macrophages.

Garlic has a variety of biologic activities, including anti-inflammatory properties. Although garlic has several biologic activities, some people dislike eating fresh raw garlic because of its strong taste and smell. Therefore, garlic formulations involving heating procedures have been developed. In this study, we investigated whether short-term heating affects the anti-inflammatory properties of garlic. Fresh and heated raw garlic extracts (FRGE and HRGE) were prepared with incubation at 25 °C and 95 °C, respectively, for 2 h. Treatment with FRGE and HRGE significantly reduced the LPS-induced increase in the pro-inflammatory cytokine concentration (TNF-α, IL-1β, and IL-6) and NO through HO-1 upregulation in RAW 264.7 macrophages. The anti-inflammatory effect was greater in FRGE than in HRGE. The allicin concentration was higher in FRGE than in HRGE. Allicin treatment showed reduced production of pro-inflammatory cytokines and NO and increased HO-1 activity. The results show that the decrease in LPS-induced NO and pro-inflammatory cytokines in RAW 264.7 macrophages through HO-1 induction was greater for FRGE compared with HRGE. Additionally, the results indicate that allicin is responsible for the anti-inflammatory effect of FRGE. Our results suggest a potential therapeutic use of allicin in the treatment of chronic inflammatory disease.

Comparison of Anti-Oxidant and Anti-Inflammatory Effects between Fresh and Aged Black Garlic Extracts

Numerous studies have demonstrated that aged black garlic (ABG) has strong anti-oxidant activity. Little is known however regarding the anti-inflammatory activity of ABG. This study was performed to identify and compare the anti-oxidant and anti-inflammatory effects of ABG extract (ABGE) with those of fresh raw garlic (FRG) extract (FRGE). In addition, we investigated which components are responsible for the observed effects. Hydrogen peroxide (H2O2) and lipopolysaccharide (LPS) were used as a pro-oxidant and pro-inflammatory stressor, respectively. ABGE showed high ABTS and DPPH radical scavenging activities and low ROS generation in RAW264.7 cells compared with FRGE. However, inhibition of cyclooxygenase-2 and 5-lipooxygenase activities by FRGE was stronger than that by ABGE. FRGE reduced PGE2, NO, IL-6, IL-1β, LTD4, and LTE4 production in LPS-activated RAW264.7 cells more than did ABGE. The combination of FRGE and sugar (galactose, glucose, fructose, or sucrose), which is more abundant in ABGE than in FRGE, decreased the anti-inflammatory activity compared with FRGE. FRGE-induced inhibition of NF-κB activation and pro-inflammatory gene expression was blocked by combination with sugars. The lower anti-inflammatory activity in ABGE than FRGE could result from the presence of sugars. Our results suggest that ABGE might be helpful for the treatment of diseases mediated predominantly by ROS.

Aged Red Garlic Extract Suppresses Nitric Oxide Production in Lipopolysaccharide-Treated RAW 264.7 Macrophages Through Inhibition of NF-κB

Lipopolysaccharides (LPS) activate nuclear factor kappa B (NF-κB), a transcription factor that is involved in inflammatory response. The pathways that activate NF-κB can be modulated by phytochemicals derived from garlic. We recently demonstrated that aged red garlic extract (ARGE), a new formulation of garlic, decreases nitric oxide (NO) generation by upregulating of heme oxygenase-1 (HO-1) in RAW 264.7 cells activated by LPS. However, the effects of ARGE on LPS-induced NF-κB activation are unknown. This study was performed to evaluate whether ARGE regulates LPS-induced NO production by modulation of NF-κB activation in macrophages. The inhibition of NF-κB by Bay 11-7085, an inhibitor of NF-κB, decreased LPS-induced NO production. ARGE treatment markedly reduced LPS-induced NO production and NF-κB nuclear translocation. ARGE downregulated expression of inducible nitric oxide synthase (iNOS) and upregulated expression of HO-1, a cytoprotective and anti-inflammatory protein. However, Bay 11-7085 only reduced iNOS expression. The NO production and iNOS expressions upregulated by suppression of HO-1 were suppressed by treatment with ARGE and Bay 11-7085. These results show that ARGE reduces LPS-induced NO production in macrophages through inhibition of NF-κB nuclear translocation and HO-1 activation. Compared to Bay 11-7085, ARGE may enhance anti-inflammatory effects by controlling other anti-inflammatory signals as well as regulation of NF-κB.

Physicochemical Properties, Biological Activity, Health Benefits, and General Limitations of Aged Black Garlic: A Review

Garlic (Allium sativum) has been used as a medicinal food since ancient times. However, some people are reluctant to ingest raw garlic due to its unpleasant odor and taste. Therefore, many types of garlic preparations have been developed to reduce these attributes without losing biological functions. Aged black garlic (ABG) is a garlic preparation with a sweet and sour taste and no strong odor. It has recently been introduced to Asian markets as a functional food. Extensive in vitro and in vivo studies have demonstrated that ABG has a variety of biological functions such as antioxidant, anti-inflammatory, anti-cancer, anti-obesity, anti-diabetic, anti-allergic, cardioprotective, and hepatoprotective effects. Recent studies have compared the biological activity and function of ABG to those of raw garlic. ABG shows lower anti-inflammatory, anti-coagulation, immunomodulatory, and anti-allergic effects compared to raw garlic. This paper reviews the physicochemical properties, biological activity, health benefits, adverse effects, and general limitations of ABG.

Inhibition of Vascular Endothelial Growth Factor Receptor 3 Reduces Migration of Gastric Cancer Cells

Angiogenesis induced by proangiogenic molecules such as vascular endothelial growth factor (VEGF) is a key process in the progression and metastasis of gastric cancer. In this study, we investigated the role of VEGF-C/VEGF receptor 3 (VEGFR3) axis in cell proliferation and migration/invasion of human gastric cancer cells (hGCCs). VEGF-C did not enhance cell proliferation but increased cell migration/invasion by approximately ∼50% in hGCCs (AGS and SNU-484). MAZ51, a VEGFR3 inhibitor, reduced the VEGF-C-induced increase in migration/invasion by ∼30% (p < 0.05). These results suggest that VEGFR3 could be a therapeutic target for reducing the metastasis of gastric cancer cells.

Upregulation of Human Mammaglobin Reduces Migration and Invasion of Breast Cancer Cells

Little is known about the biological role of human mammaglobin (hMAM) that is considered as a promising marker for breast cancer. Here, we investigated hMAMs role related to migration and invasion of human breast cancer cells (hBCC). Compared to normal cells, hBCC have high MAM mRNA expression levels. Of the hBCC tested, MAM mRNA expression levels were higher in noninvasive than in invasive cells. Overexpression of hMAM in breast cancer cells decreased migration and invasion, whereas knockdown of hMAM increased both. Taken together, these results suggest that metastasis of hBCC could be controlled by hMAM expression levels.

Lamotrigine increases intracellular Ca2+ levels and Ca2+/calmodulin-dependent kinase II activation in mouse dorsal root ganglion neurones

Lamotrigine is a neuroprotective agent that is used clinically for the treatment of seizures and neuropathic pain. A significant volume of literature has reported that lamotrigine exerts analgesic effect by blocking Ca2+ channels. However, little is known regarding the effect of lamotrigine on the intracellular Ca2+ concentration ([Ca2+]i). The aim of this study was to determine whether lamotrigine modulates [Ca2+]i in sensory neurones.