• The Korea Journal of Herbology
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• v.28 no.4
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• pp.49-55
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• 2013

Objectives : Mori Folium was popularly used as one of the traditional medicinal herbs. Although M. Folium has been cultivated for rearing silkworm historically, it's use has been expanded as natural therapeutic agent for the treatment of filariasis, diabetes and dropsy in East Asia. However, little has been known about the effect of M. Folium on liver fibrosis. Therefore, we would like to explore an anti-fibrogenic potential of M. Folium extract (MFE) using immortalized human hepatic stellate cell line, LX-2 cells. Methods : We examined the effects of MFE on the transforming growth factor ${\beta}1$ ($TGF{\beta}1$)-induced liver fibrosis in LX-2 cells. Cell viability, Smad binding element-driven luciferase activity, phosphorylations level of Smad 2/3, and expression level of $TGF{\beta}1$-dependent target genes were monitored in the MFE-treated LX-2 cells. Results : Up to 30 ${\mu}g/ml$ MFE treatment did not show any possible toxic effect in LX-2 cells. MFE inhibited $TGF{\beta}1$-inducible Smad binding element-driven luciferase activity and decreased the $TGF{\beta}1$-inducible phosphorylations of Smad 2 and Smad 3 in hepatic stellate cell in a dose dependent manner. Furthermore, increases of plasminogen activator inhibitor type 1, $TGF{\beta}1$ and matrix metalloproteinases 2 genes by $TGF{\beta}1$ were also attenuated by MFE treatment. Conclusions : These findings suggested that MFE would be used as a potential therapeutic agent for the treatment liver fibrosis, which might be mediated by the inhibition of $TGF{\beta}1$-inducible Smad 2/3 transactivation and target genes expression.

• Journal of Environmental Health Sciences
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• v.48 no.2
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• pp.106-115
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• 2022

Background: Current research suggests that humans are exposed to microplastics through consumption of foods and beverages, the airway route, and a variety of other means. Objectives: We evaluated oxidative stress and inflammation from polyethylene microplastics (PE-MPs) in the neonatal liver through intragastric administration or intratracheal instillation in pregnant mice. Methods: PE-MPs were administered from gestational day 9 to postnatal day 7. The intragastric administration group (0.01 mg/mouse/day or 0.1 mg/mouse/day) and intratracheal instillation group (6 ㎍/mouse/day or 60 ㎍/mouse/day) of PE-MPs were administered. After sacrifice, the oxidative stress and inflammation of the neonatal livers were measured. Results: As a result of the oxidative stress caused by PE-MPs in the neonatal livers, glutathione peroxidase decreased in a concentration-dependent manner in the intragastric administration group compared to the control group and intratracheal instillation decreased in high concentration PE-MPs. The catalase level increased at high concentrations of intragastric administration and intratracheal instillation. To confirm the level of inflammation caused by PE-MPs, monocyte chemoattractant protein-1 and tumor necrosis factoralpha were increased compared to the control group except for intratracheal intilation-high concentration PEMPs. The C-reactive protein level was decreased by intragastric administration compared to the control group and intratracheal instillation was increased compared to the control group. Conclusions: Despite the difficulty in comparing the toxic intensity between intragastric administration and intratracheal instillation of PE-MPs, our study revealed that oxidative stress and inflammation were induced in the neonatal liver. However, it is necessary to evaluate the toxic effects of microplastics on various organs as well. Overall, the present study indicates that the evaluation of toxic effects of long-term microplastic exposure, potential of microplastic toxicity on next-generation offspring and toxicity mechanism in human should be considered for further investigations.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.539-549
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• 2019

Background: 20(S)-Protopanaxadiol (PPD), the aglycone part of 20(S)-protopanaxadiol ginsenosides, possesses antidepressant activity among many other pharmacological activities. It is currently undergoing clinical trial in China as an antidepressant. Methods: In this study, an ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass tandem mass spectrometry method was established to identify the metabolites of PPD in human plasma and urine following oral administration in phase IIa clinical trial. Results: A total of 40 metabolites in human plasma and urine were identified using this method. Four metabolites identified were isolated from rat feces, and two of them were analyzed by NMR to elucidate the exact structures. The structures of isolated compounds were confirmed as (20S,24S)-epoxydammarane-12,23,25-triol-3-one and (20S,24S)-epoxydammarane-3,12,23,25-tetrol. Both compounds were found as metabolites in human for the first time. Upon comparing our findings with the findings of the in vitro study of PPD metabolism in human liver microsomes and human hepatocytes, metabolites with m/z 475.3783 and phase II metabolites were not found in our study whereas metabolites with m/z 505.3530, 523.3641, and 525.3788 were exclusively detected in our experiments. Conclusion: The metabolites identified using ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry in our study were mostly hydroxylated metabolites. This indicated that PPD was metabolized in human body mainly through phase I hepatic metabolism. The main metabolites are in 20,24-oxide form with multiple hydroxylation sites. Finally, the metabolic pathways of PPD in vivo (human) were proposed based on structural analysis.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.42 no.1
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• pp.1-7
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• 2009

The toxicity of two species of puffer fish, Takifugu poecilonotus (Heuinjeombok) and T. vermicularis (Gukmaeribok) collected from the coastal regions of Korea was determined using a mouse bioassay. In the T. poecilonotus collected in Jeju and Tongyeong, the proportion of toxic specimens containing ${\ge}10$ mouse units (MU) per gram exceeded 95% for the skin, liver, ovary, and fin, and approximately 30% for the testis and muscles. In each of the organs, the highest toxin levels were 79 MU/g in the muscle, hundreds (158-365) of MU per gram in the fin, intestine, testis, and gallbladder, but thousands (1,147-2,406) of MU per gram in the skin, liver, and ovary. In T. vermicularis collected from Incheon and Gunsan, the proportions of toxic specimens were 100% for the gallbladder, and 56-68% for the skin, fin, liver, and intestine however, no toxic muscle specimens were noted. The highest toxin scores were below 10 mouse units (MU) per gram in the muscle, 20-94 MU/g in the skin and fin, 319 MU/g in the intestine, and thousands (1,548-4,624) of MU per gram in the liver, gonad, and gallbladder. The toxicity in the muscle of T. vermicularis was deemed acceptable for human consumption, whereas the toxicities in the muscle of T. poecilonotus and the skin of both species of puffer fish were significantly high, such that special attention may be required when the fish is intended for human consumption.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.39 no.6
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• pp.447-453
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• 2006

Toxicity of two species of puffer fish, Takifugu porphyreus and Takifugu rubripes, collected from coastal regions of Korea, was determined using a mouse bioassay, In T. porphyreus, the proportion of toxic specimens containing ${\ge}$ 10 MU/g was 58.3% for the ovary, 32.6% for the skin, 12.0% for the gallbladder, 11.6% for the liver and intestine, and 9.3% for the fin; no toxicity was detected in the muscle and testis using the mouse bioassay. The highest toxin levels were 531 MU/g in the liver, 253 MU/g in the intestine, 136 MU/g in the gallbladder, 118 MU/g in the skin, 116 MU/g in the ovary, and 108 MU/g in the fin. The skin, which is used for human consumption, showed significantly high toxicity with an average of $11{\pm}3\;(mean{\pm}SE) MU/g$. Takifugu porphyreus toxicity also exhibited remarkable regional variation. In T. rubripes, the proportion of toxic specimens was 25.0% for the ovary, 15.8% for the liver, 11.1% for the gallbladder, and 5.3% for the fin and intestine; no toxicity was detected in the muscle, skin, or testis. Among the organs, the highest toxin levels were 228 MU/g in the ovary, followed by 112 MU/g in the liver, 28 MU/g in the gallbladder, 18 MU/g in the intestine, 11 MU/g in the fin, and 8 MU/g in the skin. Thus, we found acceptable toxin levels in the edible muscle and skin of T. rubripes and in the muscle of T. porphyreus. However, the skin of T. porphyreus, which showed significantly high toxicity, requires special attention when used for human consumption.

• The Journal of Internal Korean Medicine
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• v.21 no.1
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• pp.65-73
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• 2000

Objectives : The effects of cotreatment of adriamycin and ethanol extract of herb (Palgin-tang hab Hwajuck-hwan a traditional medicine for cancer treatment in oriental medicine) on the induction of apoptotic cell death were investigated in human liver origin cell lines, Chang. Methods : Chang(ATCC) liver cells were cultured in RPMI-1640(Gibco SRL Co, Gaithersburg, MD) badge including 10% fetal bovine serum. Chang liver cells were treated with various concentrations(from 10 to $0.16{\mu}l$) of adriamycin and herb extract(from 500 to $31.25{\mu}l$) After 48h later, the cells were tested for viability by Crystal violet staining assay. Adriamycin and Herb extract induced ladder pattern of DNA fragmentation in Chang cells. Genomic DNA was isolated and separated on 1.5% agarose gels. The DNA was stained with ethidium bromide and visualized under UV light. Results : The death of Chang cells was synergistically induced by the cotreatment of adriamycin and ethanol extract of herb. In addition, the cotreatment-induced cell death of Chang cells was mediated by apoptotic death signal processes. The phosphotransferase activity of JNK1 remained in a basal level in Chang cells which was treated individually with the adriamycin and ethanol extract of herb. However, it was markedly increased in Chang cells which was cotreated with adriamycin and ethanol extract of herb. In addition, the expression of Fas and FasL was markedly induced by the cotreatment of adriamycin and herb extract. For a while, the expression of Sax was a eminently increased by the ethanol extract of herb. However, Scl2 expression was not affected by the individual or cotreatment of adriamycin and herb extract. Conclusions : our results suggest that the cotreatment of adriamycin aM ethanol extract of herb induces synergistic apoptotis of human liver origin Chang cells via the upregulation of JNK, Fas, FasL and Bax.

• Korean Journal of Food Science and Technology
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• v.37 no.5
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• pp.822-826
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• 2005

Effect of Cheonnyuncho extract on the liver injury of rats treated carbon tetrachloride $(CCl_4)$ was studied. Cheonnyuncho extract was administerd at dose of 0.5 and 1 g/kg/day, p.o. for 2 weeks. $CCl_4$ was treated at dose of $0.5\;mL/kg$, i.p. 3 hours later from the last pretreatment of Cheonnyuncho extract. Administration of Cheonnyuncho extract at a dose of 1 g/kg decreased serum AST, ALT and ALP activities by 36, 41, and 22% respectively compared to $CCl_4$ treatment group. Increased lipid peroxidation and decreased SOD and GST activities were also recovered by pretreatment of Chonnyuncho extract in liver of rats. These results suggest that Cheonnyuncho extract has hepatoprotective effect against liver injury.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4285-4288
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• 2012

Background: Opisthorchis viverrini infection is a serious public-health problem in Southeast Asia. It is associated with a number of hepatobiliary diseases and the evidence strongly indicates that liver fluke infection is the etiology of cholangiocarcinoma. Objectives: This study aimed to determine Opisthorchis viverrini infection in elderly people in Surin province, Northeastern Thailand. Methods: A community-based cross-sectional survey was conducted among 333 elderly in 17 districts of Surin province, during one year period from January to December 2011. O. viverrini infection was determined using Kato's Thick Smear technique and socio-demographic were collected using predesigned semi-structured questionnaires, respectively. Results: A total of 333 elderly including 116 males and 217 females were selected from different study sites. Overall intestinal parasitic infection was 16.2%, predominantly in O. viverrini (9.91%) and followed by Strongyloides stercolaris (4.80%) and hookworm (1.50%), respectively. The O. viverrini infection was found higher in males (13.8%) than females (7.83%), and frequently in elderly 60-70 year old with 14.2%. Chi-square testing indicated that education and occupation were significantly associated with O. viverrini infection (P value = 0.02). The distribution of O. viverrini infection was found in 11 districts which was covered 64.7% of the studies areas. The highest prevalence was found in Thatum with 39.1%, and followed by Sangkha (24.0%), Buachet (21.1%), Samrong Thap (19.1%), Si Narong (15.0%), and Ratanaburi (13.3%) districts. Conclusion: This findings stress that O viverrini is still a problem in Thailand. We confirmed, for the first time, the high endemicity of human O. viverrini infections in elderly in Surin province of Thailand, underlying the fact that mass treatment and health education are urgently required.

• The Korea Journal of Herbology
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• v.21 no.4
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• pp.27-36
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• 2006

Objectives : This study was performed for the investigation of anticancer effects of methanol extract of Rheum Rhizoma (MeOH-RR) on a human liver cancer cell line (HepG2). Methods : To study the cytotoxic effect of MeOH-RR on HepG2 cells, the cell viability was determined by XTT reduction method and trypan blue exclusion assay. The cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of procaspase-3, -8 and -9 were examined by western blot analysis. Furthermore, MeOH-RR-induced apoptosis was confirmed by DNA fragmentation. The release of cytochrome c from mitochondria to cytosol, the level of Bcl-2 and Bax were examined by western blot analysis. Results : MeOH-RR reduced proliferation of HepG2 cells in a dose-dependent manner at 24 h and 48 h treatment. MeOH-RR induced the activation of caspase-3, -8, and -9 and the cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3. Furthermore, treatment with MeOH-RR resulted in internucleosomal DNA fragmentation, evidenced by the formation of a DNA ladder on agarose gel, a hallmark of cells undergoing apoptosis. MeOH-RR downregulated Bcl-2, upregulated Bax, and increased the release of cytochrome c from the mitochondria into cytosol in a dose-dependent manner. Moreover, MeOH-RP increased caspase-3 activity. Conclusion : There results suggest that MeOH-RR induce apoptosis via mitochondrial pathway and caspase-3-dependent pathway in HepG2 cells. There results suggest that MeOH-RR is potentially useful as a chemotherapeutic agent in human liver cancer.

• Applied Microscopy
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• v.33 no.1
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• pp.41-48
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• 2003

The hemopoiesis in human fetal spleen was studied with transmission electron microscope. There were undifferentiated proerythroblast, basophilic erythroblast, polychromatophilic erythroblast, and acidophilic erythroblast. Besides, enucleated nuclei and mitoses were present. Groups of erythroblastic cells were surrounded by certain cell. The structure was identical to erythropoietic island found in fetal liver. So, erythropoisis in spleen was developing in a pattern similar to fetal liver. Megakaryobalst were found in spleen, but there was no mature cells, cells in mitosis nor platelet formation. It was not clear whether megakaryoblast in circulation was trapped in spleen or participated in megakaryopoiesis. In summary, erythropoiesis took place in fetal spleen in a pattern similar to fetal liver and bone marrow. But it was not certain whether megakaryopoiesis took place in fetal spleen.