Eun-Ju Cho

Increase in antioxidant and anticancer effects of ginsenoside Re–lysine mixture by Maillard reaction

Ginsenosides are the main active components of Panax ginseng. Structural changes in diol type ginsenosides along with generation of Maillard reaction products (MRPs) are strongly associated with increased free radical-scavenging activities. Ginsenoside Re, one of the major triol type ginsenosides of P. ginseng, possesses a hydrophobic four-ring steroid-like structure with hydrophilic sugar moieties at carbons-3 and -20. The aim of the present study was to identify changes in the structure, antioxidant and anticancer effects of ginsenoside Re upon Maillard reaction. Ginsenoside Re was transformed into less-polar ginsenosides, namely Rg(2), Rg(6) and F(4) by heat-processing. Free radical-scavenging activity of the ginsenoside Re-lysine mixture increased upon heat processing. This improved free radical-scavenging activity mediated by antioxidant MRPs, which were generated through Maillard reaction of a glucosyl moiety separated from carbon-20 of ginsenoside Re and lysine. The increased anticancer effect of ginsenoside Re-lysine mixture upon heat processing was mainly derived from the generation of less-polar ginsenosides through the regulation of Bcl-2 and Bax, as well as caspase-dependent apoptotic pathway. These results reported here have shed significant new lights on the mechanism of increased antioxidant and anticancer effects of P. ginseng upon heat processing.

Baicalein induces apoptosis via ROS-dependent activation of caspases in human bladder cancer 5637 cells

Baicalein is a flavonoid derived originally from the root of Scutellaria baicalensis Georgi, which has been used in Oriental medicines for treating various diseases. Although this compound has been reported to have anticancer activities in several human cancer cell lines, the therapeutic effects of baicalein on human bladder cancer and its mechanisms of action have not been extensively studied. This study investigated the proapoptotic effects of baicalein in human bladder cancer 5637 cells. For this study, cell viability and apoptosis were evaluated using the 3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue dye exclusion assay 4,6-diamidino-2-phenylindole staining, and flow cytometry. Measurements of the mitochondrial membrane potential (MMP), caspase activity assays and western blots were conducted to determine whether 5637 cell death occurred by apoptosis. Treatment with baicalein resulted in a concentration-dependent growth inhibition coupled with apoptosis induction, as indicated by the results of nuclei morphology examination and flow cytometry analyses. The induction of the apoptotic cell death of 5637 cells by baicalein exhibited a correlation with the downregulation of members of the inhibitor of apoptosis protein (IAP) family, including cIAP-1 and cIAP-2, and the activation of caspase-9 and -3 accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase. The study also showed that baicalein decreases the expression of the proapoptotic protein Bax, increases antiapoptotic Bcl-2 expression, and noticeably aggravates the loss of MMP. Concomitantly, the data showed that baicalein increases the levels of death receptors and their associated ligands and enhances the activation of caspase-8 and truncation of Bid. However, the pan-caspase inhibitor can reverse baicalein-induced apoptosis, demonstrating that it is a caspase-dependent pathway. Moreover, it was found that baicalein can induce the production of reactive oxygen species (ROS) and that pretreatment with the antioxidant N-acetyl-L-cysteine significantly attenuates the baicalein effects on the loss of MMP and activation of caspase. In addition, the blocking of ROS generation decreases the apoptotic activity and antiproliferative effect of baicalein, indicating that baicalein induces apoptosis of 5637 cells through the ROS-dependent activation of caspases.

Baicalein protects C6 glial cells against hydrogen peroxide-induced oxidative stress and apoptosis through regulation of the Nrf2 signaling pathway

Baicalein, a flavonoid originally obtained from the roots of Scutellaria baicalensis Georgi, has been reported to possess various biological properties. Although several studies have demonstrated the anti-oxidative activity of baicalein, its neuroprotective mechanisms have not been clearly established. The present study aimed to detect the effects of baicalein against hydrogen peroxide (H2O2)-induced neuronal damage in C6 glial cells and to investigate the molecular mechanisms involved in this process. The results demonstrated that baicalein effectively inhibited H2O2-induced growth and reactive oxygen species (ROS) generation. We noted that Baicalein also attenuated the H2O2‑induced formation of comet tail, phosphorylation of p-γH2A.X, loss of mitochondrial membrane potential (MMP or ΔΨm), and changes to apoptosis‑related protein expression, which suggests that it can prevent H2O2‑induced cellular DNA damage and apoptotic cell death. Furthermore, treatment with baicalein effectively induced the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) as well as heme oxygenase-1 (HO-1) and thioredoxin reductase 1 (TrxR1) in a concentration and time-dependent manner. Moreover, the protective effects of baicalein against H2O2‑induced DNA damage and apoptosis were abolished by zinc protoporphyrin (ZnPP) IX, a HO-1 inhibitor, and auranofin, a TrxR inhibitor. In addition, we noted that the cytoprotective effects of baicalein were attenuated by transient transfection with Nrf2-specific small interfering RNA (siRNA). The findings of our present study suggest that baicalein enhances cellular antioxidant defense capacity through the inhibition of ROS generation and the activation of the Nrf2 signaling pathway, thus protecting C6 cells from H2O2-induced neuronal damage.

Baicalein Inhibits the Migration and Invasion of B16F10 Mouse Melanoma Cells through Inactivation of the PI3K/Akt Signaling Pathway.

Baicalein, a natural flavonoid obtained from the rhizome of Scutellaria baicalensis Georgi, has been reported to have anticancer activities in several human cancer cell lines. However, its antimetastatic effects and associated mechanisms in melanoma cells have not been extensively studied. The current study examined the effects of baicalein on cell motility and anti-invasive activity using mouse melanoma B16F10 cells. Within the noncytotoxic concentration range, baicalein significantly inhibited the cell motility and invasiveness of B16F10 cells in a concentration-dependent manner. Baicalein also reduced the activity and expression of matrix metalloproteinase (MMP)-2 and -9; however, the levels of tissue inhibitor of metalloproteinase-1 and -2 were concomitantly increased. The inhibitory effects of baicalein on cell motility and invasiveness were found to be associated with its tightening of tight junction (TJ), which was demonstrated by an increase in transepithelial electrical resistance and downregulation of the claudin family of proteins. Additionally, treatment with baicalein markedly reduced the expression levels of lipopolysaccharide-induced phosphorylated Akt and the invasive activity in B16F10 cells. Taken together, these results suggest that baicalein inhibits B16F10 melanoma cell migration and invasion by reducing the expression of MMPs and tightening TJ through the suppression of claudin expression, possibly in association with a suppression of the phosphoinositide 3-kinase/Akt signaling pathway.

The Antioxidant Effect of Hot Water Extract from the Dried Radish (Raphanus sativus L.) with Pressurized Roasting

The antiradical property of hot water extract from dried radish (DR) or dried radish roasted with pressure (DRRP) was investigated in vitro and in LLC-PK1 cell system. The contents of total free amino acid and reducing sugar in DR were decreased by 72.86% and 3.17%, respectively, after pressurized roasting. In vitro test, for DR and DRRP for DPPH radical scavenging activity were 646.70 and , 896.10 and for superoxide anion radical, and 722.26 and for hydroxy radical, respectively. The radical scavenging effects of DRRP was significantly greater than those for DR (p at which oxidative stresses were induced by superoxide, nitric oxide and peroxynitrite generated in the treatment of pyrogallol, SNP, and SIN-1, respectively. Cell viability was increased in the presence of DR or DRRP, dose dependently (p were greater than those of DR at the same concentration tested (p

Identification of anti-cancer active components of Taraxacum coreanum on human gastric cancer AGS cells

Anti-cancer effects were compared amongst Taraxacum coreanum extract, its fractions, and 7 ingredients (β-sitosterol, daucosterol, taraxasteryl acetate, chrysoeriol, diosmetin, luteolin, and luteoloside). Exposure to the ethyl acetate fraction (50 and 100 μg/mL) of T. coreanum extract and luteolin (10 and 50 μM) for 24 h induced the cleavage of poly (ADP-ribose) polymerase (PARP), caspase-3, and caspase-8, in a dose-dependent manner. These findings demonstrate that luteolin is the main active component of T. coreanum extract activating caspases-3 and -8 which contribute to apoptotic cell death.

A novel therapeutic approach of Hachimi-jio-gan to diabetes and its complications

Great efforts have been made to improve both the quality of life and life expectancy of diabetes by treating problems associated with chronic complications such as neuropathy, retinopathy and nephropathy. In particular, diabetes is an increased risk of developing several types of kidney disease, and the predominant cause of end-stage renal disease in patients with this disorder is diabetic nephropathy. Therefore, prevention of the occurrence and progression of diabetes and its complications has become a very important issue. The scientific observations of an animal model of streptozotocin-induced diabetes, spontaneously occurring diabetes and diabetic nephropathy in this study suggest that one of the Kampo prescriptions, Hachimi-jio-gan comprising eight constituents, is a novel therapeutic agent.