Protective effects of an ethanol extract of Angelica keiskei against acetaminophen-induced hepatotoxicity in HepG2 and HepaRG cells

BACKGROUND/OBJECTIVE: Although Angelica keiskei (AK) has widely been utilized for the purpose of general health improvement among Asian, its functionality and mechanism of action. The aim of this study was to determine the protective effect of ethanol extract of AK (AK-Ex) on acute hepatotoxicity induced by acetaminophen (AAP) in HepG2 human hepatocellular liver carcinoma cells and HepaRG human hepatic progenitor cells. MATERIALS/METHODS: AK-Ex was prepared HepG2 and HepaRG cells were cultured with various concentrations and 30 mM AAP. The protective effects of AK-Ex against AAP-induced hepatotoxicity in HepG2 and HepaRG cells were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, lactate dehydrogenase (LDH) assay, flow cytometry, and Western blotting. RESULTS: AK-Ex, when administered prior to AAP, increased cell growth and decreased leakage of LDH in a dose-dependent manner in HepG2 and HepaRG cells against AAP-induced hepatotoxicity. AK-Ex increased the level of Bcl-2 and decreased the levels of Bax, Bok and Bik decreased the permeability of the mitochondrial membrane in HepG2 cells intoxicated with AAP. AK-Ex decreased the cleavage of poly (ADP-ribose) polymerase (PARP) and the activation of caspase-9, -7, and -3. CONCLUSIONS: These results demonstrate that AK-Ex downregulates apoptosis via intrinsic and extrinsic pathways against AAP-induced hepatotoxicity. We suggest that AK could be a useful preventive agent against AAP-induced apoptosis in hepatocytes.

Anticancer activity of subfractions containing pure compounds of Chaga mushroom (Inonotus obliquus) extract in human cancer cells and in Balbc/c mice bearing Sarcoma-180 cells

The Chaga mushroom (Inonotus obliquus) has been used in folk medicine to treat cancers. However, limited information exists on the underlying anticancer effects of the major component of I. obliquus in vivo. We hypothesize that the pure compounds (3beta-hydroxy-lanosta-8,24-dien-21-al, inotodiol and lanosterol, respectively) separated from I. obliquus would inhibit tumor growth in Balbc/c mice bearing Sarcoma-180 cells (S-180) in vivo and growth of human carcinoma cells in vitro. To test this hypothesis, the growth inhibition of each subfraction isolated from I. obliquus on human carcinoma cell lines (lung carcinoma A-549 cells, stomach adenocarcinoma AGS cells, breast adenocarcinoma MCF-7 cells, and cervical adenocarcinoma HeLa cells) was tested in vitro. Then, after S-180 implantation, the mice were fed a normal chow supplemented with 0, 0.1 or 0.2 mg of subfraction 1, 2 or 3 per mouse per day. All of the subfractions isolated from I. obliquus showed significant cytotoxic activity against the selected cancer cell lines in vitro. Subfraction 1 was more active than subfraction 2 and subfraction 3 against the A549, AGS and MCF-7 cancer cell lines in vitro. In in vivo results, subfraction 1 isolated from I. obliquus at concentrations of 0.1 and 0.2 mg/mouse per day significantly decreased tumor volume by 23.96% and 33.71%, respectively, as compared with the control. Subfractions 2 and 3 also significantly inhibited tumor growth in mice bearing S-180 as compared with the control mouse tumor. Subfraction 1 isolated from I. obliquus showed greater inhibition of tumor growth than subfractions 2 and 3, which agrees well with the in vitro results. The results suggest that I. obliquus and its compounds in these subfractions isolated from I. obliquus could be used as natural anticancer ingredients in the food and/or pharmaceutical industry.

beta-Carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macro phages by suppressing redox-based NF-kappaB activation

beta-Carotene has shown antioxidant and antiinflammatory activities; however, its molecular mechanism has not been clearly defined. We examined in vitro and in vivo regulatory function of beta-carotene on the production of nitric oxide (NO) and PGE2 as well as expression of inducible NO synthase (iNOS), cyclooxygenase-2, TNF-alpha, and IL-1beta. beta-Carotene inhibited the expression and production of these inflammatory mediators in both LPSstimulated RAW264.7 cells and primary macrophages in a dose-dependent fashion as well as in LPS-administrated mice. Furthermore, this compound suppressed NF-kappaB activation and iNOS promoter activity in RAW264.7 cells stimulated with LPS. beta-Carotene blocked nuclear translocation of NF-kappaB p65 subunit, which correlated with its inhibitory effect on IkappaBalpha phosphorylation and degradation. This compound directly blocked the intracellular accumulation of reactive oxygen species in RAW264.7 cells stimulated with LPS as both the NADPH oxidase inhibitor diphenylene iodonium and antioxidant pyrrolidine dithiocarbamate did. The inhibition of NADPH oxidase also inhibited NO production, iNOS expression, and iNOS promoter activity. These results suggest that beta-carotene possesses anti-inflammatory activity by functioning as a potential inhibitor for redox-based NF-kappaB activation, probably due to its antioxidant activity.

A Study on Patterns of Dose for Radiation Workers in Korea / 한국역학회지

This study presents data on the externally received doses for radiation workers who used the Korea Radioisotope Association's personal monitoring and dose record keeping service from 1984. Distributions of annual dose by age of worker and occupational category were given. The number of radiation workers registered was 23,257 in 1997. The trend of the number of radiation workers and their annual doses increased since 1984. The measured radiation dose were generally low. The collective annual dose and the mean annual dose were 33.45 Sv and 1.44 mSv, respectively. Very few workers(0.5%) exceeded 20 mSv(2 rem) and only 1 exceeded 50 mSv, the legal limit for dose.

Effect of Dietary Factors in the Etiology of Stomach Cancer / 한국역학회지

BACKGROUND: Stomach cancer is the most malignant neoplasm among Koreans. There ane a number of epidemiological studies on dietary factors of stomach cancer in many countries. However, analytical studies on Korean dietary factors are very scarce. SUBJECTS AND METHODS: A case-control study was conducted at the Korea Cancer Center Hospital in Seoul between April and September in 1996. One hundred twenty-six stomach cancer patients confirmed by the histological diagnosis were compared with 234 control subjects matched by age, sex, and admission date. A food frequency questionnaire asking the consumption frequency of 85 selected food items was used to gather the information from all subjects via a face-to-face interview. Multiple logistic regression models were used to estimate relative risks when controlling simultaneously for covariates. RESULTS: An increased risk of stomach cancer was noted among those with low economic status, fast eating rate, high eating out, hot-temperature soup preference, salt preference, cucumber Kimchi intake, use of pickled fish in Kimchi. Intake of garlic, green onion, tofu, mung bean pancake, acorn-starch paste, starch vermicelli with mixed vegetables, total fruits, citrus fruits, cabbage, green peppers, spinach, mushrooms and total meat appeared to be protective. Stomach cancer risk was not associated with intake of rice, dairy product, fishes, condiments, coffee, tea, and the cooking methods. These data suggested that the high intake of salt and smoked or pickled food may be associated with a hig risk of stomach cancer, and this association could be due to a intragastric formation of nitrosamines. The negative association with fruits and some vegetable consumption may be due to the inhibition of nitrosation process. CONCLUSION: Our findings indicated that dietary factors contributed to stomach cancer occurrence in Korea, and this may offer clues for further ethnical and prevention research.

Effect of Non-dietary Factors in the Etiology of Stomach Cancer / 한국역학회지

BACKGROUND: Stomach cancer is the most malignant neoplasm among Koreans. There are some studies on risk factors for cancer prevention. SUBJECTS AND METHODS: A case-control study was conducted at the Korea Cancer Center Hospital in Seoul between April and September in 1996. One hundred twenty-six stomach cancer patients confirmed by the histological diagnosis were compared with 234 control subjects mached by age, sex, and admission date. The questionnaire included information on sociodemographic characteristics, smoking and drinking habits, height, weight, family history of cancer, nutrient supplements intake etc. Associations of stomach cancer with con-dietary factors were evaluated. Multiple logistic regression models were used to estimate relative risks when controlling simultaneously for covariates. RESULTS: Weight and body mass index(BMI, kg/m2) at diagnosis were significantly low in cases compared with controls. As non-dietary factors, smoking habits, alcoholic beverage, family gistory, physical activity, water supply, stress, vitamin suppliments and the use of functional foods were not associated with stomach cancer risk. CONCLUSION: Our findings indicated that non-dietary factors were not associated with stomach cancer risk.