• 동의생리병리학회지
• /
• 제30권1호
• /
• pp.20-26
• /
• 2016

Prunellae Spica, the herbaceous plant in the genus Prunella, is a traditional herbal medicine and has been reported to have diuretic, anti-bacterial and anti-oxidant effects. However, the mechanism of its action was not clearly identified. In the present study, we investigated the hepatoprotective effect of Prunellae Spica extract (PSE) against the damage of mitochondria and death in hepatocyte induced by oxidative stress. Treatment of arachidonic acid (AA)+iron significantly induced oxidative stress and apoptosis in the hepatocytes. However, PSE protected cells and inhibited apoptosis by altering the protein levels such as poly(ADP-ribose) polymerase and pro-caspase 3. Moreover, AA+iron induced reactive oxygen species production and mitochondrial dysfunction, and Both of them were inhibited by PSE treatment. PSE markedly activated AMP-activated protein kinase (AMPK), an important regulator in cell survival. Furthermore, this activation by PSE was mediated with liver kinase B1, a major upstream kinase that phosphorylates Thr 172 of AMPKα, and this activation was associated with its cell protection, as assessed by an experiment of a chemical inhibitor. In conclusion, this study demonstrate that PSE protects hepatocytes against oxidative stress as mediated with activation of LKB1-dependent AMPK pathway.

• Food Science and Biotechnology
• /
• 제14권1호
• /
• pp.99-101
• /
• 2005

The effect of treatment with pine needle oil upon rat hepatocytes exposed to alcohol was investigated. The body weight gain, ratio of liver and kidney to body weight, and serum biochemistry of rats administered both alcohol and pine needle oil were compared to control rats treated with alcohol alone. Normal untreated control rats, negative control rats with ethanol treatment, positive control rats with both alcohol and the commercially available hangover cure solution (HCS) treatment and the test group with both alcohol and pine needle oil treatment exhibited aspartate aminotransferase (AST) levels of $84.43{\pm}47.88\;U/L$, $254.57{\pm}463.20\;U/L$, $70.29{\pm}12.60\;U/L$ and $67.00{\pm}5.06\;U/L$, respectively, and cholesterol levels of $95.71{\pm}6.86\;mg/dl$, $113.80{\pm}38.19\;mg/dl$, $91.57{\pm}6.30\;mg/dl$ and $82.29{\pm}4.98\;mg/dl$, respectively. Alanine aminotransferase (ALT) levels were $44.00{\pm}9.04\;U/L$ in normal untreated control rats, increased to $215.43{\pm}428.93\;U/L$ with the administration of ethanol, but interestingly were significantly reduced to $37.83{\pm}6.57\;U/L$ in the test group (p<0.05). Triglyceride (TG) levels were $39.57{\pm}8.62\;mg/dl$ in normal untreated rats, increased to $73.71{\pm}61.20\;mg/dl$ in rats administered alcohol, but were reduced to $26.14{\pm}4.82\;mg/dl$ in the test group (p<0.0l). The pine needle oil treatment significantly reduced the levels of AST, ALT and TG compared to the control rats. These results indicate that pine needle oil can positively mediate the effects of alcohol on hepatocytes and general liver functions.

• Natural Product Sciences
• /
• 제14권2호
• /
• pp.95-99
• /
• 2008

In a project to study the hepatroprotective effect of some plant extracts four plants Ephedra foliate Boiss, Alhagi maurorum Medikus, Capsella bursa-pastoris (L.) Medik. and Hibiscus sabdariffa L. were studied. The ethanol extract of the aerial part of the first three plants and the flowers of H. sabdariffa were subjected to hepatoprotective assays using Wistar albino rats. Liver injury induced in rats using carbon tetrachloride. The biochemical parameters; serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP) and total bilirubin were estimated as reflection of the liver condition. Based on the good results of the biochemical parameters measurements, histopathological study was performed on the liver of rats treated with E. foliate. The normal appearance of hepatocytes indicated a good protection of the extract from carbon tetrachloride hepatotoxicity. All the results were compared with silymarin, the reference hepatoprotective drug.

• 식품과학과 산업
• /
• 제51권4호
• /
• pp.334-342
• /
• 2018

People in Korea, a peninsular, have acquired a variety of marine food resources including seaweeds. Ecklonia stolonifera, a brown algae, is commonly dwelling in Korean coasts and their cultivation methods were developed for a mass-production. Recently, studies have revealed that Ecklonia stolonifera is a promising material for the development of health functional foods. In an effort to carefully review the current understating in the effects and mechanisms of Ecklonia stolonifera on liver functions by deduction from relevant literatures, the effective components were identified as phlorotannins, including dieckol, eckstolonol, eckol, phlorofucofuroeckol A, and phlorosterol. Their aiding action on the hepatic functions is categorized as follows. A) Regulation of oxidative stress by anti-oxidant capacity, B) Protection of hepatocytes from toxins, C) Prevention of alcoholic fatty liver and fibrogenesis, D) Regulation of chronic disease by improvement of inflammatory responses and lipid metabolisms, and E) indirect benefit conferred by a personal total wellness.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.132.1-132.1
• /
• 2003

Biphenyl dimethyl dicarboxylate (DDB) is a by-product produced in process of synthesizing Schizandrin-C. Generally, DDB has known to protect hepatocytes and to decrease the index of liver enzyme (e.g. GOT and GPT) in chronic hepatitis. The present study was aimed to demonstrate whether DDB can protect the brain cell, especially the Alzheimer brain in vitro. As Alzheimers disease can be induced by activated microglia, a macrophage in the brain, through Abeta peptide (A$\beta$) produced from amyloid precursor protein (APP). (omitted)

• 동의생리병리학회지
• /
• 제29권1호
• /
• pp.18-26
• /
• 2015

Akebiae Caulis is a galenical originated from Akebia quinata Decaisne species. It is commonly used in the treatment of oposiuria, inflammation, nociceptive and fever. Here, we investigated the effect of Akebiae Caulis extract (ACE) to protect hepatocyte against the malfunction of mitochondria and apoptosis. Arachidonic acid (AA)+iron promoted excessive reactive oxygen species (ROS) production and exerted a deleterious effect on mitochondria. Treatment with ACE protected hepatocytes from AA+iron-induced cytotoxicity, as shown by alterations in the protein levels related with apoptosis such as poly(ADP-ribose) polymerase, pro-caspase 3, Bcl-XL and Bcl-2. Moreover, AA+iron-induced $H_2O_2$ production, GSH depletion and mitochondrial dysfunction were alleviated by ACE pretreatment. As a potential molecular mechanism for the ACE-mediated cytoprotection, phosphorylation of AMP-activated protein kinase (AMPK), a key regulator in determining cell survival or death, was increased by ACE. Moreover, ACE treatment enhanced inactive phosphorylation of glycogen synthase kinase-$3{\beta}$ ($GSK3{\beta}$), downstream substrate kinase of AMPK. More importantly, ACE prevented a decrease in the $GSK3{\beta}$ phosphorylation derived by AA+iron, which might contribute to mitohondiral protection and cell survival. To further identify essential compounds in Akebiae Caulis for the protection of AA+iron-mediated cytotoxicity, we found that betulin in combination with hederagenin protected from AA+iron-induced mitochondrial dysfunction. Betulin+hederagenin treatment also increased inactive phosphorylation of $GSK3{\beta}$ in common with ACE. These results suggest that ACE protected hepatocytes against oxidative stress and mitochondrial dysfunction, which is mediated with inactive $GSK3{\beta}$ phosphorylation downstream of AMPK.

• 한국자원식물학회:학술대회논문집
• /
• 한국자원식물학회 2021년도 춘계학술대회
• /
• pp.5-5
• /
• 2021

Alcoholic and nonalcoholic steaohepatitis is a leading form of chronic liver disease with few biomakers ad treatment options currently available. a progressive disease of NAFLD may lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Recently, we extracted HIMH0021, which is an active flavonoid component in the Acer tegmentosum extract, has been shown to protect against liver damage caused by hepatic dysfunction. Therefore, in this study, we aimed to investigate whether HIMH0021 could regulate steatohepatitis and liver fibrosis during alcoholic or nonalcoholic metabolic process. HIMH0021, which was isolated from the active methanol extract of A. tegmentosum, inhibited alcohol-induced steatosis and attenuated the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during hepatocellular alcohol metabolism, both of which promote lipogenesis as well as liver inflammation. Treatment with HIMH0021 conferred protection against lipogenesis and liver injury, inhibited the expression of cytochrome P4502E1, and increased serum adiponectin levels in the mice subjected to chronic-plus-binge feeding. Furthermore, in hepatocytes, HIMH0021 activated fatty acid oxidation by activating pAMPK, which comprises pACC and CPT1a. These findings suggested that HIMH0021 could be used to target a TNFα-related pathway for treating patients with alcoholic hepatitis.

• 한국식품저장유통학회지
• /
• 제30권5호
• /
• pp.797-810
• /
• 2023

Elaeagnus umbellata leaves have been reported to suppress inflammation, allergic responses, lung cancer proliferation and oral bacterial growth. Cadmium (Cd) is a heavy metal that has been found to cause many toxicities, including liver toxicity. The aim of this study was to evaluate the capacity of 70% ethanol extract of E. umbellata leaves (EUL) to protect human hepatocytes from Cd toxicity. After exposure of HepG2 cells to Cd at 10 𝜇M for 24 h, cell viability, expression levels of apoptosis- and antioxidant-related proteins, reactive oxygen species (ROS) accumulation and Cd uptake were assessed. EUL protected HepG2 cells from Cd-induced apoptosis as determined by MTT assay. A decrease in caspase-3 and p-p53 protein levels was observed in cells pretreated with EUL prior to Cd exposure. Furthermore, the Cd-induced increase in intracellular DCF fluorescence was attenuated by EUL, indicating that the Cd-induced apoptosis preventing effect was associated with the suppression of ROS accumulation. Moreover, EUL's effects on the inhibition of p38, JNK, and AKT phosphorylation also appear to be associated with protection against Cd toxicity. Moreover, EUL upregulated Cd-depressed expression of Nrf2, HO-1, catalase, and MT-1,2 proteins, suggesting that Cd uptake-induced apoptosis in HepG2 cells may be inhibited by EUL's antioxidative potential.

• 대한본초학회지
• /
• 제30권6호
• /
• pp.7-15
• /
• 2015

Objectives : Rosa laevigata Michx. has been used for the treatment of renal disease in traditional Korean medicine. In this study, we investigated cytoprotective effect of R. laevigata water extract (RLE) against oxidative stress induced by arachidonic acid (AA) + iron.Methods : To evaluate the protective effects of RLE against AA + iron-induced oxidative stress in HepG2 cell, cell viability and changes on apoptosis-related proteins were assessed by MTT and immunoblot analyses. The effects of RLE on reduced glutathione level, production of reactive oxygen species and mitochondrial membrane potential were also monitored. Furthermore, to verify underlying molecular mechanism, NF-E2-related factor 2 (Nrf2) was examined by immunoblot analysis. Additionally, Nrf2 transactivation and its downstream target genes expression were also determined by reporter gene and realtime RT-PCR analyses.Results : RLE pretreatment (30-300 μg/ml) prevented cells from AA + iron-mediated cell death in a concentration dependent manner. In addition, 100 μg/ml RLE inhibited AA + iron-induced glutathione depletion, reactive oxygen species production and mitochondrial dysfunction. RLE accumulated nuclear Nrf2 and also transactivated Nrf2, which was evidenced by antioxidant response element- and glutathione S-transferase A2-driven luciferase activities and mRNA level of glutamate-cysteine ligase catalytic subunit, NAD(P)H:quinone oxidoreductase 1 and sestrin 2. Moreover, protective effect of RLE against AA + iron was abolished in Nrf2 knockout cells.Conclusions : These results indicate that RLE has the ability to protect hepatocyte against oxidative stress through Nrf2 activation.

• 대한임상독성학회지
• /
• 제17권2호
• /
• pp.58-65
• /
• 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.