• Toxicological Research
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• v.31 no.4
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• pp.403-414
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• 2015

Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes.

• Proceedings of the Korean Society of Postharvest Science and Technology of Agricultural Products Conference
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• 1996.04a
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• pp.25-25
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• 1996

;Jindo Hongju is an unique red-colored traditional distilled wine of Korea. The unique attractive color of Jindo Hongju is due to the pigments of gromwell (Lithospermum erythrorhizon) root, derivatives of naphtoquinone such as shikonin and acetylshikonin. Which are extracted during the distillation process. The attractive color of the gromwell pigments is easily changed to dark red or to brown causing deterioration of the Quality of Jindo Hongju. Due to the discoloration of the pigments and to the limited supply of gromwell roots, some brewers manufacture spurious Jindo Hongju using artificial colorants. This study was performed to devise a simple method of detecting spurious Jindo Hongju products. The color of the gromwell pigments was greatly affected by pH change and the change could be demonstrated by the change of the absorption spectrum. At pH 4.0 the normal pH of Jindo Hongju, the absorption spectra of gromwell pigments and genuine Hongju products showed an absorption maximum of 520 nm. The absorption maximum was shifted to 570 nm and to 616 nm as the pH was raised to 7.0 and 11.0 respectively. This transition due to the pH change was also demonstrated on em chromaticity diagram. The characteristic transition due to pH change of gromwell pigment solution was not observed with an artificial colorant (red No.2) which was suspected to be used in the manufacture of imitation products. The absorption spectra of most of the Jindo Hongju collected from the market were similar to that of the gromwell pigments and showed the characteristic transition due to pH change with the addition of NaOH. However, with a few of the products, the absorption spectra was similar to that of the artificial colorant and the characteristic transition due to pH change was not observed, indicating these products might have been forged. The result of study suggests that the transition of the absorption spectrum and the change of the color due to pH change be used for the detection of imitation products. Farther more, since, at pH above 9.0, the color of the gromwell pigments and genuine Jindo Hongju could be visually differentiated from that of the artificial colorant and forged products, it might be possible that the forged products be easily detected by raising the pH to above 9.0 and visually comparing the color with that of the gromwell pigment at the same pH.me pH.

• Molecules and Cells
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• v.43 no.3
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• pp.236-250
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• 2020

Currently, many available anti-cancer therapies are targeting apoptosis. However, many cancer cells have acquired resistance to apoptosis. To overcome this problem, simultaneous induction of other types of programmed cell death in addition to apoptosis of cancer cells might be an attractive strategy. For this purpose, we initially investigated the inhibitory role of TRIP-Br1/XIAP in necroptosis, a regulated form of necrosis, under nutrient/serum starvation. Our data showed that necroptosis was significantly induced in all tested 9 different types of cancer cell lines in response to prolonged serum starvation. Among them, necroptosis was induced at a relatively lower level in MCF-7 breast cancer line that was highly resistant to apoptosis than that in other cancer cell lines. Interestingly, TRIP-Br1 oncogenic protein level was found to be very high in this cell line. Up-regulated TRIP-Br1 suppressed necroptosis by repressing reactive oxygen species generation. Such suppression of necroptosis was greatly enhanced by XIAP, a potent inhibitor of apoptosis. Our data also showed that TRIP-Br1 increased XIAP phosphorylation at serine87, an active form of XIAP. Our mitochondrial fractionation data revealed that TRIP-Br1 protein level was greatly increased in the mitochondria upon serum starvation. It suppressed the export of CypD, a vital regulator in mitochondria-mediated necroptosis, from mitochondria to cytosol. TRIP-Br1 also suppressed shikonin-mediated necroptosis, but not TNF-α-mediated necroptosis, implying possible presence of another signaling pathway in necroptosis. Taken together, our results suggest that TRIP-Br1/XIAP can function as onco-proteins by suppressing necroptosis of cancer cells under nutrient/serum starvation.