• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7785-7792
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• 2014

Background: Valproic acid (VPA) is a potent anticancer and antiangiogenic agent. However, design and synthesis of chemical derivatives with improved antiangiogenic and anticancer activities are still necessary. In this study a library of novel derivatives of VPA was synthesized and tested. Methods: A human liver cancer cell line (HepG2) and a human normal embryonic kidney cell line (HEK 293) were exposed to various concentrations of VPA derivatives for 24 hours and cell viability was checked by MTT colorimetric assay. Anti-angiogenic properties were evaluated in transgenic zebrafish embryos. Results: N-valproylglycine derivatives suppressed survival almost 70% (p value 0.001) in HepG2 cells but only 10-12% in HEK 293 cells (p value 0.133). They also suppressed angiogenic blood vessel formation by 80% when used between $2-20{\mu}M$ in zebrafish embryos. Valproic acid hydrazides showed moderate level of anticancer activity by affecting 30-50% (p value 0.001) of cell viability in HepG2 cells and 8-10% in HEK293 cells (p value 0.034). Conclusion: The majority of compounds in this study showed potent and stronger antiangiogenic and anticancer activity than VPA. They proved selectively toxic to cancer cells and safer for normal cells. Moreover, these compounds inhibited developmental angiogenesis in zebrafish embryos. Based on the fact that liver is a highly vascularized organ, in case of liver carcinoma these compounds have the potential to target the pathological angiogenesis and could be an effective strategy to treat hepatocellular carcinoma.

• 대한한방내과학회지
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• 제29권1호
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• pp.177-188
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• 2008

Objectives : This study was performed to investigate the anti-fibrogenic effect of Artemisiae Capillaris Herba on cultured rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells(HSC-T6) were treated with various concentrations of Artemisiae Capillaris Herba extract for 24 hours. The extraction was done either with distilled water or 50% EtOH. After the treatment, cell viability, proliferation, procollagen levels and the mRNA of the collagen type 1a2 and ASMA were measured by using MTT assay, BrdU assay, RT-PCR, and Procollagen Type I C-peptide EIA Kit. Results : The viability and proliferation of the hepatic stellate cells were decreased as the concentration increased. The mRNA expression decreased consistently with the volume of the secreted procollagen with the extraction made with distilled water, which indicates the herb has inhibitory effect on fibrogenesis of the liver by regulating one of the fibrosis associated genes in transcription. However, it increased in 50% EtOH extraction, which shows that a more stable reaction is expected of the extraction made with distilled water than the extraction made with 50% EtOH. The production of procollagen was decreased by a low-concentration treatment with Artemisiae Capillaris Herba, but increased by a high concentration. It seemed that the cells were responding to Artemisiae Capillaris Herba in low- concentrations, thus producing small amounts of collagen. When the drug was administered at high enough concentration to give direct toxicity to cells, the ability of cells to produce collagen was activated, and the overproduction of collagen was observed as an undesirable results. Conclusion : These results suggest that Artemisiae Capillaris Herba is beneficial in the treatment of cirrhotic patients as well as for the patients with chronic hepatitis when extracted with water in the proper concentrations.

• Applied Microscopy
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• 제23권2호
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• pp.41-52
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• 1993

본 연구에서는 반수서동물인 Suncus Murinus간실질의 구조와 간소엽에 존재하는 간실질세포, 동모양내피 세포, Kupffer세포 및 Ito세포의 미세구조를 관찰하고 이들의 특징을 포유동물 및 비포유동물의 것들과 비교 고찰하였다. 간실질세포는 지방소적과 비교적 큰 사립체를 많이 함유하고 있었으며 세포간격은 좁았으나 세포 표면은 가늘고 긴 돌기를 많이 갖고 있어 그 미세구조가 비포유동물의 일부 동물종에 유사한 소견을 나타냈다. 내피세포 또한 일부 비포유동물에 있어서와 같이 용해소체를 많이 함유하고 있어 Kupffer세포와의 식별이 어려웠다. 간소엽에는 담세관이 많았으며 일부 담세관과 담관은 Disse강에서 관찰되었는데 이러한 담관계는 Disse강에 있는 소세포와 간실질세포에 의해서 형성되어있거나 소세포들이 내강을 둘러 싸면서 형성하고 있었다. 담관계형성에 관여하는 소세포들은 지방소적을 함유하거나 함유하지 않은 Ito세포일 것으로 추정되었다. 이상의 소견으로 미루어 Suncus Murinus간장은 포유동물과 비포유동물의 구조와 미세구조를 동시에 갖추고 있는 것같이 보인다.

• 대한본초학회지
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• 제24권3호
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• pp.79-86
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• 2009

Objectives : The present study investigated Inflammatory effect of Coptidis Rhizoma in lipopolysaccharideexposed rats and Raw 264.7 cells. Methods： The plasma concentration of IL-1$\beta$, IL-6 and TNF-$\alpha$ peaked at 5 h after LPS injection, and the values of the Coptidis Rhizoma extract groups were lower than those of the control group. In the increment of cytokines concentration at 2 h and 5 h after LPS injection, the Coptidis Rhizoma groups were lower than that of control group. The plasma concentration of IL-10 peaked at 5 h after LPS injection, and the values of the Coptidis Rhizoma extract groups were higher than those of the control group. In the increment of cytokines concentration at 2 h and 5 h after LPS injection, the Coptidis Rhizoma groups were higher than that of control group. Liver cytokines measurement was done at 5 h after LPS injection. The concentration of liver IL-1$\beta$ and IL-6 in the Coptidis Rhizoma groups was lower than that of the control group. The concentrations of liver TNF-$\alpha$, and IL-10 showed no significant differences among all the treatment groups. Results： In the studies of lipopolysaccharide-exposed Raw 264.7 cells, the concentration of IL-1$\beta$, IL-6 and TNF-$\alpha$ in the lipopolysaccharide-exposed cells groups was higher than that of control group (normal group), and in the lipopolysaccharide-exposed cells groups, these values showed a tendency to decrease in the Coptidis Rhizoma groups. The concentration of IL-10 in the lipopolysaccharide-exposed cells groups was higher than that of control group (normal group), and in the lipopolysaccharide-exposed cells groups, the values showed a tendency to increase in the Coptidis Rhizoma groups. Conclusions： These results indicate that the Coptidis Rhizoma extracts have an functional material for Inflammatory activities.

• Journal of Nutrition and Health
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• 제17권4호
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• pp.253-261
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• 1984

식이중 지방 수준과 fiber 종류가 흰 쥐의 혈청과 간 조직내의 지질 함량에 미치는 영향을 알아보기 위해 지방 수준을 0% , 5% , 20% 수준으로 달리 하였으며 fiber 종류는 고지방 식이군( 20% 지방 )에 pectin과 cellulose를 각각 10% 수준으로 첨가하였다. 또 식이내 cholesterol첨가의 효과를 관찰하기 위해 고지방 식이군에 0.5% cholesterol을 첨가한 후 pectin과 cellulose를 10%씩 넣어 전체적으로 7군으로 나누어 각 각 다른 식이로 4주간 사양한 후 혈청과 간에서 지질 함량을 조사하였으며 간 조직의 형태학적 조사를 실시하여 다음과 같은 결과를 얻었다. 1) 식이 섭취량은 지방 수준이 낮을수록 높았으나 뚜렷한 차이는 보이지 않았으며 pectin과 cellulose 첨가로 인해서 섭취량이 줄었다. 증체량은 지방 수준이나 fiber종류에 따라 큰 차이를 보이지 않았다. 변의 무게는 지방 수준에 따른 차이는 없었으나 fiber 첨가로 인해서는 pectin은 약간의 감소를 cellulose 는 뚜렷한 증가를 보였다. 또 cholesterol을 첨가한 군 간의 비교에서도 pectin첨가군은 감소를 cellulose첨가군은 증가를 나타냈다. 간과 epididymal fat pad의 무게는 지방 수준이 높아짐에 따라 증가하였으며 fiber 종류에 따라서는 pectin첨가군이 cellulose 첨가 군 보다 낮았다. 2) 혈청 분석 결과는 식이내 지방 수준이 높을수록 total lipids수준이 높아지는 경향을 보였으며 pectin이 cellulose보다 혈청내 지질 수준을 뚜렷하게 낮추었다. Total cholesterol 및 phospholipids 량에 있어서도 지방 수준이 증가함에 따라 높아졌으며 cellulose보다 pectin이 첨가 되었을때 현저한 감소를 나타냈다. HDL- cholesterol수준은 무지방군에서는 매우 높게 나타났으나 표준군과 고지방군간에 는 명확한 결과를 얻을 수 없었다. 3) 간 분석 결과는 지방수준이 높을수록 total lipids량이 높아지는 경향을 보였다. 또 pectin 첨가가 cellulose첨가군보다 현저히 낮은 lipids수준을 나타냈다. 간의 total cholesterol함량은 지방 수준이 높아짐에 따라 증가하였으나 뚜렷한 차이는 아니었으며 pectin첨가가 cellulose첨가보다 cholesterol 수준이 상당히 낮았다. 4) 간 조직의 현미경 관찰 결과는 지방 수준이 높아짐에 따라 조직내 지방 침착이 심해졌으며 fiber 의 첨가로 인해서는 pectin은 뚜렷한 지방 침착의 감소를 보였으나 cellulose는 거의 감소 효과를 보이지 않았다.

• 약학회지
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• 제49권6호
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• pp.505-510
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• 2005

Allylthio group of allicin and other organosulfur compounds which are isolated from garlic is considered as a pharmacophore, a key structure component of the molecule which is responsible biological activities. In the foregoing studies various 3-allylthio -6- alkoxypyridazine derivatives (K- compounds ) and 3-allylthio -6- alkylthiopyridazine derivatives(Thio-K-compounds) were synthesized and their biological activities were tested in vivo. They showed good hepatoprotective activities on the carbon tetrachloride-treated mouse and aflatoxin Bl-treated rat and chemopreventive activities on bepatocarcinoma cells in rat as expected. Now 3-allylthio-6-heterocyclylalkylaminopyridazine derivatives that the oxygen atom at 6-Position of 3-allylthio-6-alkoxypyridazine is replaced by nitrogen (N) were synthesiz ed and their activities were tested in vitro against SK-Hep-1 human liver cancer cells. They showed good chemopreventive activities on hepatocarcinoma cells.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.255.1-255.1
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• 2002

We investigated the anti-proliferative effects of lxeris sonchifolia H. (godulbaegi) root extracts. luteolin(3'. 4', 5. 7-Q-glucoside and 3'. 4', 5, 7-tetrahydoxyflavone) and apigenin (3', 4'. 5. 7-O-gluconic acid) on HepG2 (p53 wild type) cells. Hep3B (p53 null) cells, and Chang liver cells. In MTT assay 3', 4'.5. 7-tetrahydoxyflavone showed the most efficient anti-proliferative effects on these three cell lines. However, there was no significant anti-proliferative effect on Chang liver cell line in MTT results. (omitted)

• 대한한의학회지
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• 제41권4호
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• pp.64-71
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• 2020

Objectives: This study was done to look into whether Nrf2 take some role in the anti-lipogenic effect of kaurenoic acid in a nonalcoholic fatty liver disease (NAFLD) cellular model. Materials and Methods: We measured the effect of kaurenoic acid on intracellular steatosis and Nrf2 activation. Next, the effect of kaurenoic acid on SREBP-1c and some lipogenic genes in palmitate treated HepG2 cells with or without Nrf2 silencing. Results: The increased SREBP-1c expression was significantly decreased by concomitant kaurenoic acid treatment in non-targeting negative control siRNA transfected HepG2 cells. However, kaurenoic acid did not significantly inhibited increased SREBP-1c level in Nrf2 specific siRNA transfected HepG2 cells Conclusions: Kaurenoic acid has a potential to activate Nrf2, which may suppress SREBP-1c mediated intracellular steatosis in HepG2 cells.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2023년도 임시총회 및 춘계학술대회
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• pp.43-43
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• 2023

In this study, we investigated in vitro inhibitory activity of wild-simulated ginseng (WSG) against non-alcoholic fatty liver disease using HepG-2 cells. T0901317 treatment increased the lipid accumulation in HepG-2 cells, but WSG treatment inhibited T0901317-mediated lipid accumulation. In addition, WSG downregulated T0901317-mediated expression of SREBP-1c, ACC, FAS and SCD-1 protein. In addition, WSG increased the phosphorylation level of LKB1 and AMPK. Compound C treatment blocked WSG-mediated downregulation of SREBP-1c protein. In conclusion, WSG is considered to inhibit the accumulation of lipids and triglycerides in HepG-2 cells by inducing the activation of LKB1 and AMPK successively, thereby reducing the expression of FAS, ACC, and SCD-1 through suppression of SREBP-1c expression.

• 대한한의학방제학회지
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• 제28권3호
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• pp.255-269
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• 2020

Objectives : Hemistepta lyrata Bunge (Bunge) is a wild herb that has been used for managing fever and wound in Korean Traditional Medicine. The present study explored the effects of H. lyrata extract on liver X receptor (LXR) α-dependent lipogenic genes in hepatocyte-derived cells. Methods : After HepG2 cells or Huh7 cells were pre-treated with 1-10 ㎍/mL of H. lyrata extract or its fractionated extract for 0.5 h, the cells were subsequently exposed to LXR ligand for 6-24 h. Cell viability, LXR response element (LXRE)-driven luciferase activity, sterol regulatory element binding protein-response element (SREBP-RE)-driven luciferase activity, SREBP-1c expression, and mRNA levels of LXRα and its-dependent target genes were determined. In addition, LC-MS/MS analysis was conducted to explore major compounds in H. lyrata-chloroform fractionated extract #4 (HL-CF4). Results : Of various H. lyrata extracts tested, chloroform extract and its fractionated extract #4, HL-CF4, significantly decreased T0901317-mediated SREBP-1c expression. In addition, HL-CF4 significantly reduced LXRE atransactivation and LXRα mRNA expression without any cytotoxicity. Moreover, HL-CF4 prevented the SREBP-RE-driven luciferase activity and mRNA levels of fatty acid synthase and stearoyl-CoA desaturase-1 induced by T0901317. Results from LC-MS/MS analysis at positive/negative mode indicated that HL-CF4 contained several compounds showing m/z 197.1176 (C₁₁H₁₇O₃), 693.2913/227.1069 (C₃₈H₄₅O₁₂/C₁₅H₁₅O₂), 203.1797 (C₁₅H₂₃), 181.1225 (C₁₁H₁₇O₂), 591.2957 (C₃₅H₄₃O₈), 379.1040 (C₁₈H₁₉O₉), 409.1509 (C₂₀H₂₅O₉), 309.1348 (C₁₆H₂₁O₆), 391.1404 (C₂₀H₂₃O₈), and 669.2924/389.1248 (C₃₆H₄₅O₁₂/C₂₀H₂₁O₈). Conclusion : Based on its inhibition of the LXRα-dependent signaling pathway, H. lyrata chloroform extract and HL-CF4 have prophylactic potentials for managing non-alcoholic fatty liver.