Purpose: This study was conducted to establish whether an ethanol extract of Lycium barbarum leaves (LLE) and an ethanol extract of Lycium barbarum leaves from which chlorophyll has been removed, denoted as LLE(Ch-), have a protective effect against hepatic fat accumulation. Methods: The inhibitory effects of LLE and LLE(Ch-) on liver fat accumulation were examined in C57BL/6 mice with non-alcoholic fatty liver disease (NAFLD) induced by an methionine and choline deficient diet and in HepG2 cells with palmitic acid-induced fat accumulation. Results: The plasma triglyceride, aspartate aminotransferase, and alanine aminotransferase levels were lower in the LLE(Ch-) group, whereas the plasma ALT activity decreased significantly in the LLE group. In both the LLE and the LLE(Ch-) groups, the triglyceride and cholesterol contents in the hepatic tissue were significantly reduced. A greater inhibitory effect on tissue fat accumulation was observed in the LLE(Ch-) group than in the LLE group. In HepG2 cells, LLE and LLE(Ch-) were non-toxic up to a concentration of 1,000 ㎍/mL. Compared to the control group, intracellular fat accumulation in the LLE and LLE(Ch-) groups were significantly reduced at concentrations of 200 ㎍/mL and 500 ㎍/mL, respectively. The expression of phosphorylated adenosine monophosphate-activated protein kinase and phosphorylated acetyl-CoA carboxylase in both LLE groups increased at the concentrations of 100 ㎍/mL and 500 ㎍/mL. The fatty acid synthase expression was suppressed in a concentration-dependent manner at 10 ㎍/mL. Conclusion: The examined two ethanol extracts of LLE inhibit hepatic fat accumulation in NAFLD. This effect was more pronounced in the LLE(Ch-) group. Therefore, these 2 extracts have an anti-steatosis effect and can be used for NAFLD treatment.
Han Chang-Woo;Kim Young-Chul;Woo Hong-Jung;Lee Jang-Hoon
The Journal of Internal Korean Medicine
/
v.25
no.1
/
pp.59-70
/
2004
Objectives : Previous studies showed that treatment with Chungganhaeju-tang prevents hepatic inflammation and apoptosis in alcoholic liver disease. The purpose of our study is to determine if any relations exsists between the transcription factor $NF{\kappa}B$, an orchestrating expression of a large number of genes and inhibitory effects of Chungganhaeju-tang on ethanol induced apoptosis. Materials and Methods : To assess the role of $NF{\kappa}B$, we blocked NFkB activation by delivering to the kupffer cells $I{\kappa}B{\Delta}N$, a dominant negative $NF{\kappa}B$ inhibitor, and investigated if Chungganhaeju-tang still prevented apoptosis. Results : When $NF{\kappa}B$ activation was blocked, there was no inhibitory effect of Chungganhaeju-tang on ethanol induced apoptosis of kupffer cells. Conclusion : This result suggests that Chungganhaeju-tang protects the liver from ethanol induced apoptosis by activating the $NF{\kappa}B$ that plays a key role in porotecting mechanism and reducing inflammatory cytokine gene expression.
To check the possible application of our anti-AFP monocional antibodies (MAbs) as immunodiagnostic reagents for hepatocellular carcinoma, ELISA and immunohistochemical assay were performed on the sera and liver biopsy specimens from the patients of hepatocellular carcinoma and other non-malignant hepatic disease. By non-competitive ELISA using anti-AFP MAbs, the highest incidence of AFP value was found only in the sera of hepatocellular carcinoma patients, i.e., more than 54% of patients had serum AFP levels of more than 500 ng/mi. By immunoperoxidase and indirect immunofluorescence techniques, anti-AFP MAbs were found to react with cytoplasm of hepatoceliular carcinoma cells. However immunohistochemical reactIvity to AFP in hepatocellular carcinoma cells was lower than that in non-neoplastic liver cells adjacent to the hepatocellular carcinoma. From these results with the similar findings from other studies, we suggest that AFP antigen is appropriate in the diagnosis assay (ELISA) but is not by immunohistochemical detection.
Despite recent advancements in the diagnosis and treatment of pancreatic cancer, clinical results remain dismal. Furthermore, there are no reliable biomarkers or alternatives beyond carbohydrate antigen 19-9. Circulating tumor cells (CTCs) may be a potential biomarker, but their therapeutic application is constrained by their rarity in peripheral venous blood. Theoretically, the portal vein can be a more appropriate location for the detection of CTCs, because the first venous drainage of pancreatic cancer is portal circulation. According to several studies, the number and detection rate of CTCs may be higher in the portal blood than in the peripheral blood. CTC counts in the portal blood are strongly correlated with several prognostic parameters such as hepatic metastasis, recurrence after surgery, and survival. The phenotypic and genotypic properties analyzed in the captured portal CTCs can assist us to comprehend tumor heterogeneity and predicting the prognosis of pancreatic cancer. The investigations to date are limited by small sample sizes and varied CTC detection techniques. Therefore, a large number of prospective studies are required to confirm portal CTCs as a valid biomarker in pancreatic cancer.
The authors has observed the histopathologically and histochemically on the effect of the garlic and garlic oil to the liver and kidney of rats. In order to confirm the histochemical changes of the metabolism of polysaccarides, the periodic acid Schiff reaction was applied. The 30 albino adult male rats weighing about 150 grames from the National Institute of Health were housed individualy and devide into 3 experimental groups: Group C: stock diet group Group B: stock diet-garlic group Group A: stock diet-garlic oil group Group C was fed with stock diet only through out this experimental period, Group B was fed with stock diet supplemented with garlic homogenator to be 1%, and Group A was fed with stock diet supplemented with the garlic oil to 0.05%. The garlic oil used in this experiments was extracted by author. And all rats was fed during 10 weeks. The histopathological and histochemical results were shown in each figure. According to the all results, the following concIusions were drawn. 1) In the garlic oil administrated groups, congestion of the sinusoid was subsided and the liberation of the Kupffer's cells were observed. 2) In garlic administrated groups, fatty metamorphosis in hepatic cells, and slight liberation of Kupffer's cells in sinusoidal walls were observed. Connective tissue proliferation and collagen bundle were observed. 3) The connective tissue and blood vessel wall in portal area Were reacted intensely with PAS stain. The hepatic cells Were reacted intensely with PAS stain in control group and moderately or slightly in garlic and garlic oil administrated group. 4) There were no significant differences in collecting and Henle's loops in each groups, but narrowing of lumen of the distal tubules were observed in garlic oil administrated group. 5) The basement membrane of the tubules and the connective tissues of the vessel wall in Kideny were reacted intensely with PAS stain in each groups. In control and garlic administrated groups. the brush border of the proximal tubules were reacted intensely with PAS stain, but epithelium of the Heine's loop, proximal, distal and collecting tubules were reacted moderately. In garlic oil administrated-group, there were tendency of decreasing of PAS stain in each tubules.
Park, Eun-Mi;Kim, Soo-Jung;Ye, Eun-Ju;Bae, Man-Jong;Jo, Kyeong-Cheol
Journal of the Korean Society of Food Science and Nutrition
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v.34
no.3
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pp.323-329
/
2005
This study was conducted to investigate the effect of mycelia extracts of mushroom-cultured ginseng by-product on electron donating ability and proliferation of hepatic cancer cell (Hep3B) lines and sarcoma 180(S-180). The ginseng by-product was obtained from ginseng residues generated in processing of ginseng water extract. Mushroom strains used for preparation of mushroom mycelia cultured with ginseng residue were Phellinus linteus, Ganoderma lucidum, Coriolus versicolor and Lentinus edodes. The electron donating abilities of the test samples were increased in a dose-dependent manner in the range of 500ppm to 10,000ppm, and Coriolus versicolor extract showed the most potent activity among four mycelia extracts. In an anti-cancer test using Hep3B cells, ethanol extract showed higher antiproliferating effect than water extract. Ethanol extract of Lentinus edodes showed growth-inhibitory effect of 99.1% at 5,000ppm. All of mycelia extracts of mushroom showed the tumor suppressive effect in mice injected with S-180 cells. The growthinhibitoy rates against tumor cells were 59% for Phellinus linteus, 61% for Ganoderma lucidum, 65% for Coriolus versicolor, 56% for Lentinus edodes. In conclusion, these results suggest that mycelia extracts of mushroom cultured with ginseng by-product have an antiproliferating effect against Hep3B cell and S-180 tumor cells.
Park, Mi-Young;Jang, Hwan-Hee;Lee, Jin-Young;Lee, Young-Min;Kim, Jae-Hyun;Park, Jae-Hak;Park, Dong-Sik
Journal of the Korean Society of Food Science and Nutrition
/
v.41
no.4
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pp.501-509
/
2012
The dietary intake of whole grains is known to reduce the incidence of chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer. In our previous study, hog millet (HM, $Panicum$$miliaceum$ L.) water extract showed the highest anti-lipogenic activity among nine cereal types in 3T3-L1 cells. In this study, the effect of hog millet water extract on hepatic steatosis and lipid metabolism in mice fed a high fat diet was investigated. Mice were fed a normal-fat diet (ND), high-fat diet (HFD) or HFD containing 1% or 2% (w/w) HM for 7 weeks. Body weight and food intake were monitored during the study period. Insulin resistance by homeostasis model assessment (HOMA-IR), fasting lipid profile, hepatic fatty acid metabolism-related gene expression determined, and intraperitoneal glucose tolerance test (IGTT) were performed at the study's end. The results indicated that 1% and 2% HM diets effectively decreased liver weights, blood TG and T-cholesterol levels (p<0.05), while the HDL-cholesterol level was increased (p<0.05) compared to HFD-induced steatotsis mice. Hepatic lipogenic-related gene ($PPAR{\alpha}$, L-FABP, and SCD1) expressions decreased, whereas lipolysis- related gene (CPT1) expression increased in animals fed the 2% PME diet (p<0.05). In addition, mice fed 1% or 2% HM diet had markedly decreased IGTT and HOMA-IR, compared to the those of the HFD-induced hepatic steatosis control group (p<0.05). These results indicated that HM inhibited hepatic lipid accumulation by regulating fatty acid metabolism, and suggested that HM is useful in the chemoprevention or treatment of high fat-induced hepatic steatosis and hepatic steatosis-related disorders including hyperlipidemia, glucose sensitivity, and insulin resistance.
Targeted therapy has been a very promising strategy of drug development research. Many molecular mechanims of diseases have been known to be regulated by abundance of proteins, such as receptors and hormones. Chemoprevention for treatment and prevention of diseases are continuously developed. Pre-clinical and clinical studies in chemoprevention field yielded many valuable data in preventing the onset of disease and suppressing the progress of their growth, making chemoprevention a challenging and a very rational strategy in future researches. Natural products being rich of flavonoids are those fruits belong to the genus citrus. Ethanolic extract of Citrus reticulata and Citrus aurantiifolia peels showed anticarcinogenic, antiproliferative, co-chemotherapeutic and estrogenic effects. Several examples of citrus flavonoids that are potential as chemotherapeutic agents are tangeretin, nobiletin, hesperetin, hesperidin, naringenin, and naringin. Those flavonoids have been shown to possess inhibition activity on certain cancer cells' growth through various mechanisms. Moreover, citrus flavonoids also perform promising effect in combination with several chemotherapeutic agents against the growth of cancer cells. Some mechanisms involved in those activities are through cell cycle modulation, antiangiogenic effect, and apoptosis induction.Previous studies showed that tangeretin suppressed the growth of T47D breast cancer cells by inhibiting ERK phosphorylation. While in combination with tamoxifen, doxorubicin, and 5-FU, respectively, it was proven to be synergist on several cancer cells. Hesperidin and naringenin increased cytotoxicitity of doxorubicin on MCF-7 cells and HeLa cells. Besides, citrus flavonoids also performed estrogenic effect in vivo. One example is hesperidin having the ability to decrease the concentration of serum and hepatic lipid and reduce osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as natural product to be developed as not only the source of co-chemotherapeutic agents, but also phyto-estrogens. Therefore, further study needs to be conducted to explore the potential of citrus fruits in overcoming cancer.
Wang, Li-yuan;Wu, Jing;Gao, Ya-fen;Lin, Duo-mao;Ma, Jun
The Korean Journal of Physiology and Pharmacology
/
v.24
no.1
/
pp.19-26
/
2020
Medium- and long-chain triglyceride (MCT/LCT) propofol is widely used as an intravenous anesthetic, especially in the intensive care unit. The present study aimed to assess whether MCT/LCT propofol is safe in the hyperlipidemic population for long-term use. Free fatty acids (FFAs) were used to establish high-fat stimulation of HepG2 and Huh7 cells. Subsequently, these cells were treated with propofol at the concentration of 0, 4, or 8 ㎍/ml for 24 and 48 h. The results indicated that the cell viability was notably decreased when the cells were stimulated with 2 mmol/L FFAs and treated with 12 ㎍/ml MCT/LCT propofol. Accordingly, we chose 2 mmol/L FFAs along with 4 and 8 ㎍/ml MCT/LCT propofol for the subsequent experiments. Four and 8 ㎍/ml MCT/LCT propofol inhibited FFA-induced lipid accumulation in the cells and significantly reversed acetyl coenzyme A carboxylase (ACC) activity. In addition, MCT/LCT propofol not only significantly promoted the phosphorylation of AMPK and ACC, but also reversed the FFA-induced decreased phosphorylation of AMPK and ACC. In conclusion, MCT/LCT propofol reverses the negative effects caused by FFAs in HepG2 and Huh7 cells, indicating that MCT/LCT propofol might positively regulate lipid metabolism.
Objectives : Induction of CYP2E1 by ethanol is believed to be one of the major mechanism by which ethanol generate a state of oxidative stress. Previous studies showed that treatment with Chungganhaeju-tang prevents hepatic inflammation and apoptosis in alcoholic liver disease. The purpose of our study is to determine if Chungganhaeju-tang can also protect against alcohol-induced cytotoxicity in CYP2E1-transfected HepG2 cells. Materials and Methods : CYP2E1-transfected HepG2 cells and control vector-transfected HepG2 cells were exposed for isx hours to Chungganhaeju-tang, and then 50 mM of ethanol was added and left for two days. Results : Ethanol significantly decreased cell viability in CYP2E1-transfected HepG2 cells and increased apoptosis. These alterations were attenuated by Chungganhaeju-tang. This was accompanied by an improvement of NF-${\kappa}B$ and Akt activation. Conclusion : These results suggest that Chungganhaeju-tang exerts inhibitory effect against the cytotoxicity induced by alcohol in CYP2E1-transfected HepG2 cells, and that this is a protective action due, at least in part, to an activation of NF-${\kappa}B$ that plays a key role in the protection mechanism, and in reducing hepatotoxic cytokine gene expression.
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