• Maxillofacial Plastic and Reconstructive Surgery
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• v.40
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• pp.44.1-44.17
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• 2018

Background: Coffee extract has been investigated by many authors, and many minor components of coffee are known, such as polyphenols, diterpenes (kahweol and cafestol), melanoidins, and trigonelline, to have anti-inflammatory, anti-oxidant, anti-angiogenic, anticancer, chemoprotective, and hepatoprotective effects. Therefore, it is necessary to know its pharmacological effect on hepatocytes which show the most active cellular regeneration in body. Methods: In order to determine whether coffee extract has a beneficial effect on the liver, 20 C57BL/6J mice were intraperitoneally injected once with dialyzed coffee extract (DCE)-2.5 (equivalent to 2.5 cups of coffee a day in man), DCE-5, or DCE-10, or normal saline (control), and then followed by histological observation and IP-HPLC (immunoprecipitation high performance liquid chromatography) over 24 h. Results: Mice treated with DCE-2.5 or DCE-5 showed markedly hypertrophic hepatocytes with eosinophilic cytoplasms, while those treated with DCE-10 showed slightly hypertrophic hepatocytes, which were well aligned in hepatic cords with increased sinusoidal spaces. DCE induced the upregulations of cellular proliferation, growth factor/RAS signaling, cellular protection, p53-mediated apoptosis, angiogenesis, and antioxidant and protection-related proteins, and the downregulations of NFkB signaling proteins, inflammatory proteins, and oncogenic proteins in mouse livers. These protein expression changes induced by DCE were usually limited to the range ± 10%, suggesting murine hepatocytes were safely reactive to DCE within the threshold of physiological homeostasis. DCE-2.5 and DCE-5 induced relatively mild dose-dependent changes in protein expressions for cellular regeneration and de novo angiogenesis as compared with non-treated controls, whereas DCE-10 induced fluctuations in protein expressions. Conclusion: These observations suggested that DCE-2.5 and DCE-5 were safer and more beneficial to murine hepatocytes than DCE-10. It was also found that murine hepatocytes treated with DCE showed mild p53-mediated apoptosis, followed by cellular proliferation and growth devoid of fibrosis signaling (as determined by IP-HPLC), and subsequently progressed to rapid cellular regeneration and wound healing in the absence of any inflammatory reaction based on histologic observations.

• Proceedings of the Zoological Society Korea Conference
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• 1997.04a
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• pp.59.2-59
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• 1997

No Abstract, See Full Text

• Journal of Ginseng Research
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• v.39 no.2
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• pp.105-115
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• 2015

Background: Alcoholic steatosis is the earliest and most common liver disease, and may precede the onset of more severe forms of liver injury. Methods: The effect of Korean Red Ginseng extract (RGE) was tested in two murine models of ethanol (EtOH)-feeding and EtOH-treated hepatocytes. Results: Blood biochemistry analysis demonstrated that RGE treatment improved liver function. Histopathology and measurement of hepatic triglyceride content verified the ability of RGE to inhibit fat accumulation. Consistent with this, RGE administration downregulated hepatic lipogenic gene induction and restored hepatic lipolytic gene repression by EtOH. The role of oxidative stress in the pathogenesis of alcoholic liver diseases is well established. Treatment with RGE attenuated EtOH-induced cytochrome P450 2E1, 4-hydroxynonenal, and nitrotyrosine levels. Alcohol consumption also decreased phosphorylation of adenosine monophosphate-activated protein kinase, which was restored by RGE. Moreover, RGE markedly inhibited fat accumulation in EtOH-treated hepatocytes, which correlated with a decrease in sterol regulatory element-binding protein-1 and a commensurate increase in sirtuin 1 and peroxisome proliferator-activated receptor-a expression. Interestingly, the ginsenosides Rb2 and Rd, but not Rb1, significantly inhibited fat accumulation in hepatocytes. Conclusion: These results demonstrate that RGE and its ginsenoside components inhibit alcoholic steatosis and liver injury by adenosine monophosphate-activated protein kinase/sirtuin 1 activation both in vivo and in vitro, suggesting that RGE may have a potential to treat alcoholic liver disease.

• Parasites, Hosts and Diseases
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• v.62 no.1
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• pp.30-41
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• 2024

The dense granule protein of Toxoplasma gondii, inhibitor of signal transducer and activator of transcription 1 (IST) is an inhibitor of signal transducer and activator of transcription 1 (STAT1) transcriptional activity that binds to STAT1 and regulates the expression of inflammatory molecules in host cells. A sterile inflammatory liver injury in pathological acute liver failures occurs when excessive innate immune function, such as the massive release of IFN-γ and TNF-α, is activated without infection. In relation to inflammatory liver injury, we hypothesized that Toxoplasma gondii inhibitor of STAT1 transcription (TgIST) can inhibit the inflammatory response induced by activating the STAT1/IRF-1 mechanism in liver inflammation. This study used IFN-γ and TNF-α as inflammatory inducers at the cellular level of murine hepatocytes (Hepa-1c1c7) to determine whether TgIST inhibits the STAT1/IRF-1 axis. In stable cells transfected with TgIST, STAT1 expression decreased with a decrease in interferon regulatory factor (IRF)-1 levels. Furthermore, STAT1 inhibition of TgIST resulted in lower levels of NF-κB and COX2, as well as significantly lower levels of class II transactivator (CIITA), iNOS, and chemokines (CLXCL9/10/11). TgIST also significantly reduced the expression of hepatocyte proapoptotic markers (Caspase3/8/9, P53, and BAX), which are linked to sterile inflammatory liver injury. TgIST also reduced the expression of adhesion (ICAM-1 and VCAM-1) and infiltration markers of programmed death-ligand 1 (PD-L1) induced by hepatocyte and tissue damage. TgIST restored the cell apoptosis induced by IFN-γ/TNF-α stimulation. These results suggest that TgIST can inhibit STAT1-mediated inflammatory and apoptotic responses in hepatocytes stimulated with proinflammatory cytokines.

• Journal of The Korean Society of Clinical Toxicology
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• v.17 no.2
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• pp.58-65
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• 2019

Purpose: Alpha-amanitin induces potent oxidative stress and apoptosis, and may play a significant role in the pathogenesis of hepatotoxicity. This study examined the mechanisms of α-amanitin-induced apoptosis in vitro, and whether green tea extract (GTE) offers protection against hepatic damage caused by α-amanitin (AMA) induced apoptosis in vivo. Methods: The effects of GTE and SIL on the cell viability of cultured murine hepatocytes induced by AMA were evaluated using an MTT assay. Apoptosis was assessed by an analysis of DNA fragmentation and caspase-3. In the in vivo protocol, mice were divided into the following four groups: control group (0.9% saline injection), AMA group (α-amanitin 0.6 mg/kg), AMA+SIL group (α-amanitin and silibinin 50 mg/kg), and AMA+GTE group (α-amanitin and green tea extract 25 mg/kg). After 48 hours of treatment, the hepatic aminotransferase and the extent of hepatonecrosis of each subject was evaluated. Results: In the hepatocytes exposed to AMA and the tested antidotes, the cell viability was significantly lower than the AMA only group. An analysis of DNA fragmentation showed distinctive cleavage of hepatocyte nuclear DNA in the cells exposed to AMA. In addition, the AMA and GTE or SIL groups showed more relief of the cleavage of the nuclear DNA ladder. Similarly, values of caspase-3 in the AMA+GTE and AMA+SIL groups were significantly lower than in the AMA group. The serum AST and ALT levels were significantly higher in the AMA group than in the control and significantly lower in the AMA+GTE group. In addition, AMA+GTE induced a significant decrease in hepatonecrosis compared to the controls when a histologic grading scale was used. Conclusion: GTE is effective against AMA-induced hepatotoxicity with its apoptosis regulatory properties under in vitro and in vivo conditions.

• The Journal of Dong Guk Oriental Medicine
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• v.6 no.1
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• pp.107-115
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• 1997

Hapatic tissues of ICR mouse intraperitoneally injected with Triton WR-1339 were observed to investigate the morphologic change of liver by destruction of lipid metabolism as hyperlipidemia. The hepatic tissues were obtained at hour-24, 48, and 72 after triton injection that were fixed in fromol-calcium solution and were cryocut. These tissues were stained by H&E for general morphology, sudan black B for lipid, and perchloric acid-naphthoquinone method for cholesterol. The increase of hepatocyte having meshlike cytoplasm were shown in all hepatic lobules after triton injection and the hepatic plates were disappeared in the region aggregated meshlike hepatocyte. The number of blue black colored lipid drop and dark green colored asterisk shaped cholesterol particle in hepatic cytoplasm were increased than the saline injected mouse and the size of lipid drop was enlarged. As results indicated that the lipid metabolism were destructed by triton injection, subsequently hepatocyes accumulated with lipid including cholesterol.

• Journal of Microbiology and Biotechnology
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• v.31 no.7
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• pp.1011-1021
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• 2021

The root bark of Ulmus davidiana var. japonica (Japanese elm) is used in Korea and other East Asian countries as a traditional herbal remedy to treat a variety of inflammatory diseases and ailments such as edema, gastric cancer and mastitis. For this study, we investigated the lipid metabolism and anti-obesity efficacy of ethyl alcohol extract of Ulmus davidiana var. japonica root bark (UDE). First, HPLC was performed to quantify the level of (+)-catechin, the active ingredient of UDE. In the following experiments, cultured 3T3-L1 pre-adipocytes and high-fat diet (HFD)-fed murine model were studied for anti-obesity efficacy by testing the lipid metabolism effects of UDE and (+)-catechin. In the test using 3T3-L1 pre-adipocytes, treatment with UDE inhibited adipocyte differentiation and significantly reduced the production of adipogenic genes and transcription factors PPARγ, C/EBPα and SREBP-1c. HFD-fed, obese mice were administered with UDE (200 mg/kg per day) and (+)-catechin (30 mg/kg per day) by oral gavage for 4 weeks. Weight gain, epididymal and abdominal adipose tissue mass were significantly reduced, and a change in adipocyte size was observed in the UDE and (+)-catechin treatment groups compared to the untreated control group (^***p < 0.001). Significantly lower total cholesterol and triglyceride levels were detected in UDE-treated HFD mice compared to the control, revealing the efficacy of UDE. In addition, it was found that lipid accumulation in hepatocytes was also significantly reduced after administration of UDE. These results suggest that UDE has significant anti-obesity and lipid metabolism effects through inhibition of adipocyte differentiation and adipogenesis.

• Herbal Formula Science
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• v.31 no.4
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• pp.253-264
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• 2023

Objectives : Bambusae Caulis in Liquamen (BCL), a traditional herbal medicine, is a distilled product of condensation from the burning of fresh bamboo stems. We previously identified the anti-oxidant capacity of BCL in hepatocytes and suggested that BCL is a promising therapeutic candidate for treating oxidative stress-induced hepatocellular damage. Despite the importance of the role played by Kupffer cells in liver disease, the efficacy of BCL on Kupffer cells is unclear. Therefore, this study aimed to determine whether BCL could suppress LPS-induced inflammation and LPS+ATP-induced inflammasomes in Kupffer cells. Methods : We used ImKCs, a murine immortalized Kupffer cell line to examined whether BCL inhibited LPS-induced inflammation response and oxidave stress. And, we prepared a total of 18 L of BCL, purchased from Bamboo Forest Foods Co., Ltd. (648 Samdari, Damyang-eup, Damyang-gun, Jeollanam-do, Republic of Korea), was concentrated using a decompression concentrator. Result : The LPS-induced release of inflammatory cytokines was abolished by BCL treatment. Also, BCL treatment suppressed the LPS+ATP-induced expression of inflammasome proteins (NLRP3, IL-1, and IL-18), and inhib β ited the release of IL-1 . BCL decreased LPS-or LPS+ATP-induc β ed reactive oxygen species production. In addition, BCL increased nuclear translocation of Nrf2 and the expression of HO-1 in a time-dependent manner. Conclusion : These results suggest the efficacy of BCL with respect to its anti-inflammatory and anti-inflammasome effects mediated by Nrf2 in Kupffer cells.

• Biomedical Science Letters
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• v.5 no.1
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• pp.85-93
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• 1999

Nitric oxide (NO) plays an important role in immunologic defense, and influences upon the functioning of secretory tissues and cells. It also exhibits cytotoxic/cytostatic activity as one of major operating effectors of the cellular immunity system. We investigated the effects of serum on the cell damages and NO production in the mouse liver cell line BNL CL.2 to establish the role of NO. We observed that, when BNL CL.2 cells were cultured in serum-free medium, they were induced to cell damage by the stimulation of IFN-$\gamma$ alone or IFN-$\gamma$ plus LPS. Serum-starved cells showed large amount of nitrite accumulation and NO synthase (NOS) expression in response to IFN-$\gamma$ alone in dose- and time- dependent manners, but serum-supplied cells did not The production of NO was blocked by protein tyrosine kinase (PTK) inhibitors, genistein and herbimycin. These results suggest that the deprivation of serum in the BNL CL.2 cell culture medium might primed with the cells to produce NO when the cells are triggered by IFN-$\gamma$ and the involvement of PTK signal transduction pathway in the expression of NOS gene in murine hepatocytes.

• Journal of Life Science
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• v.34 no.1
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• pp.1-8
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• 2024

Brain-type natriuretic peptide (BNP) is a cardiac hormone that exerts cardiovascular and renal effects and regulates metabolic processes. In the current study, to determine the hepatic effects of BNP, we investigated whether it improves high-fat diet (HFD)-induced hepatic IR and characterized its possible mechanism. No significant differences in body weight, fat mass, or lean mass were observed between the saline- and BNP-treated groups of normal diet-and HFD-fed mice. During the clamp test, the BNP infusion into HFD-fed mice led to lower blood glucose levels and increased glucose infusion rates versus that into saline-treated HFD-fed mice. The BNP infusion also inhibited hepatic glucose production and decreased hepatic triglyceride levels concomitant with decreased expression of gluconeogenesis and lipogenesis-related genes, resulting in reduced levels of alanine aminotransferase and aspartate aminotransferase. BNP increased the phosphorylation of Akt and AMP-acti- vated protein kinase (AMPK) in the livers of HFD-fed mice compared to saline-fed HFD mice. The incubation of AML12 murine hepatocytes with BNP increased the basal levels of phosphorylated Akt and AMPK and recovered the phosphorylated Akt and phosphorylated AMPK levels reduced by palmitate treatment. Furthermore, BNP incubation prevented palmitate-induced increases in lipo- genesis gene expressions. Taken together, the current study's findings indicated that BNP ameliorates hepatic IR, resulting in reduced hepatic glucose production and hepatic steatosis.