Garlic has been used throughout history for both culinary and medicinal purpose. Allicin is a major component of crushed garlic. Although it is sensitive to heat and light and easily metabolized into various compounds such as diallyl disulfide, diallyl trisulfide, and diallyl sulfide, allicin is still a major bioactive compound of crushed garlic. The mortality of hepatocellular carcinoma is quite high and ranks among the top 10 cancer-related deaths in Taiwan. Although numerous studies have shown the cancer-preventive properties of garlic and its components, there is no study on the effect of allicin on the growth of human liver cancer cells. In this study, we focused on allicin-induced autophagic cell death in human liver cancer Hep G2 cells. Our results indicated that allicin induced p53-mediated autophagy and inhibited the viability of human hepatocellular carcinoma cell lines. Using Western blotting, we observed that allicin decreased the level of cytoplasmic p53, the PI3K/mTOR signaling pathway, and the level of Bcl-2 and increased the expression of AMPK/TSC2 and Beclin-1 signaling pathways in Hep G2 cells. In addition, the colocalization of LC3-II with MitoTracker-Red (labeling mitochondria), resulting in allicin-induced degradation of mitochondria, could be observed by confocal laser microscopy. In conclusion, allicin of garlic shows great potential as a novel chemopreventive agent for the prevention of liver cancer.

Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer globally and ranks first among the cancer-related mortalities in Taiwan. This study aims to understand the modes of cell death mechanism induced by allicin, a major phytochemical of crushed garlic, in human hepatoma cells. Our earlier study indicated that allicin induced autophagic cell death in human HCC Hep G2 (p53(wild type)) cells, whereas in the present study, allicin induced apoptotic cell death through caspase-dependent and caspase-independent pathways by reactive oxygen species (ROS) overproduction in human HCC Hep 3B (p53(mutation)) cells. To gain insight into the cell death mechanism in p53 knocked down Hep G2, we silenced the p53 gene using siRNA-mediated silencing. Allicin treatment induced apoptotic cell death in p53 knocked down Hep G2 cells similar to that of Hep 3B cells. These results suggest that allicin induced cell death in human hepatoma cells through either autophagy or apoptosis and might be a potential novel complementary gene therapeutic agent for the treatment of apoptosis-resistant cancer cells.

Fatty liver is significantly associated with hepatic cirrhosis and liver cancer. Excessive alcohol consumption causes alcoholic fatty liver disease (AFLD). Ginger has been reported to exhibit antioxidant potential and hepatoprotective activity. In the present study, a mouse model for AFLD was developed by employing male C57BL/6 mice that were fed an alcohol-containing liquid diet (Lieber-DeCarli diet) ad libitum. In the treatment groups, ginger essential oil (GEO) and citral were orally administered every day for 4 weeks. Serum biochemical analysis, antioxidant enzyme activity analysis, and histopathological evaluation revealed that GEO and citral exhibited hepatoprotective activity against AFLD. Metabolites in serum samples were profiled by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS). Metabolomic data indicated the amounts of metabolites such as d-glucurono-6,3-lactone, glycerol-3-phosphate, pyruvic acid, lithocholic acid, 2-pyrocatechuic acid, and prostaglandin E1 were increased after alcohol administration, but the levels were recovered in treatment groups. The analysis indicated that ginger possesses hepatoprotective properties against AFLD. Furthermore, these metabolites can serve as early noninvasive candidate biomarkers in the clinical application of AFLD for health management.

Fatty liver induced by alcohol abuse is a major worldwide health hazard leading to morbidity and mortality. Previous studies indicate antifatty liver properties of garlic. This study investigated the molecular mechanisms of garlic oil (GO) or diallyl disulfide (DADS) imparted hepatoprotection against alcohol induced fatty liver in C57BL/6 mice using microarray-based global gene expression analysis. Alcohol liquid diet resulted in severe fatty liver with increased levels of serum aspartate aminotransferease and alanine aminotransferease as well as triglycerides and decreased levels of liver glutathione and antioxidant enzymes. The major canonical pathways implicated by alcohol treatment are the metabolisms of xenobiotics by cytochrome P450, glutathione, and arachidonic acid. Treatment with DADS or GO normalized the serum aminotransferease levels and liver antioxidant enzymes and reduced the contents of triglycerides and cholesterol. The canonical pathways involved in the amelioration of liver include arachidonic acid metabolism, altered T cell and B cell signaling, tryptophan metabolism, antigen presentation pathway for DADS, metabolism of xenobiotics, mitotic roles of Polo-like kinase, fatty acid metabolism, LPS/IL-1 mediated inhibition of RXR function, and C21-steroid hormone metabolism for GO.