• The Journal of Internal Korean Medicine
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• v.42 no.6
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• pp.1269-1284
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• 2021

Objectives: Phragmitis Rhizoma is the fresh or dried rhizome of Phragmites communis Trin., which has been prescribed in traditional Korean medicine to relieve fever and vomiting and to nourish the body fluids. Recently, the protective effect of Phragmitis Rhizoma extract or its components on myelotoxicity and inflammatory responses have been reported, but no study has yet been conducted on oxidative stress. Methods: The present study investigated whether an ethanol extract of Phragmitis Rhizoma (PR) could protect against cellular damage induced by oxidative stress in Chang liver cells. Results: Pretreatment with PR significantly suppressed the hydrogen peroxide (H₂O₂)-induced reduction of Chang cell viability and generation of reactive oxygen species (ROS), thereby deferring apoptosis. PR also markedly inhibited H₂O₂-induced comet tail formation and phospho-γH2AX expression, suggesting that PR protected against oxidative stress-mediated DNA damage. PR also effectively prevented the inhibition of ATP synthesis in H₂O₂-treated Chang cells by inhibiting the loss of mitochondrial membrane potential, indicating that PR maintains energy metabolism through preservation of mitochondrial function while eliminating ROS generated by H₂O₂. Immunoblotting results indicated that PR attenuated the H₂O₂-induced downregulation of Bcl-2 and upregulation of Bax expression. Conclusions: PR protects against oxidative injury in Chang liver cells by regulating energy homeostasis via ROS generation blockade, which is at least partly mediated through inactivation of the mitochondria-mediated apoptosis pathway.

• Herbal Formula Science
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• v.26 no.3
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• pp.207-221
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• 2018

Objectives : Present study investigated hepatoprotective effect of Haegan-jeon extract (HE) and tried to elucidate molecular mechanism involved. According to molecular mechanism, present study optimized herbal composition of HE (op-HE) and compared in vitro and in vivo hepatoprotective effects of op-HE to HE. Methods : For in vitro experiments, HepG2 cells were exposed to arachidonic acid (AA, $10{\mu}M$) and iron ($5{\mu}M$) for inducing oxidative stress. Cell viability, GSH contents, $H_2O_2$ production, mitochondrial membrane potential, immunoblot and reporter gene assay were performed to investigate cytoprotective effects and responsible molecular mechanisms. For in vivo experiments, hepatoprotective effect of HE and op-HE were assessed on $CCl_4-induced$ liver injury mice model. Results : HE pretreatment prevented AA+iron-mediated hepatocytes apoptosis. In addition, AA+iron-induced mitochondrial dysfunction, $H_2O_2$ production, glutathione depletion were reduced by HE pretreatment. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation, antioxidant response element (ARE)-driven reporter gene activity, and antioxidant genes expression were increased by HE. Based on reporter gene and MTT assays, we found that op-HE consisting three medicinal herbs also significantly increased transactivation of Nrf2 and reduced the AA+iron-mediated cytotoxicity. Moreover, in $CCl_4-induced$ liver injury mice model, HE-op had an ability to ameliorate $CCl_4-mediated$ increases in serum alanine transferase and aspartate aminotransferase activity, hepatic degeneration, inflammatory cell infiltration, and collagen deposition. Hepatoprotective effects of op-HE were comparable to those of HE. Conclusions : Present study suggests that op-HE as well as HE exhibit hepatoprotective effect against oxidative stress-mediated liver injury via Nrf2 activation.

• Nutrition Research and Practice
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• v.6 no.2
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• pp.113-119
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• 2012

Guinea pigs were fed a hypercholesterolemic diet (0.25 g/100 g cholesterol) and randomly allocated either to a Control group (n = 9) or to a Lutein (0.1 g/100 g) group (n = 10) for 12 weeks to evaluate oxidative stress and inflammation in both liver and eyes. Malondialdehyde (MDA) concentrations and inflammatory cytokines were measured as well as hepatic nuclear factor-kappaB (NF-${\kappa}B$) binding. Lutein concentrations were greater in eyes ($P$ < 0.01) and liver ($P$ < 0.001) in the Lutein group. All guinea pigs had high concentrations of hepatic cholesterol as well as high plasma ALT and AST levels indicative of liver injury. However, the Lutein group had 43% lower hepatic free cholesterol than the Controls ($P$ < 0.05). Hepatic MDA and MDA in the eye were lower in the Lutein compared to the Control group ($P$ < 0.05). Hepatic tumor necrosis factor-${\alpha}$ was 32% lower in the Lutein group ($P$ < 0.05). Lastly, the Lutein group presented lower NF-${\kappa}B$ DNA binding activity than the Control group ($P$ < 0.001). These results suggest that in the presence of high cholesterol, lutein exerts both antioxidant and anti-inflammatory effects, which can be explained by attenuated NF-${\kappa}B$ DNA binding activity. Furthermore, results also suggest that lutein accumulates in the eyes of guinea pigs to protect against oxidative stress.

• Journal of Ginseng Research
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• v.43 no.1
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• pp.10-19
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• 2019

Background: Frequent overdose of paracetamol (APAP) has become the major cause of acute liver injury. The present study was designed to evaluate the potential protective effects of ginsenoside Rk1 on APAP-induced hepatotoxicity and investigate the underlying mechanisms for the first time. Methods: Mice were treated with Rk1 (10 mg/kg or 20 mg/kg) by oral gavage once per d for 7 d. On the 7th d, allmice treated with 250mg/kg APAP exhibited severeliverinjury after 24 h, and hepatotoxicitywas assessed. Results: Our results showed that pretreatment with Rk1 significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor, and interleukin-$1{\beta}$ compared with the APAP group. Meanwhile, hepatic antioxidants, including superoxide dismutase and glutathione, were elevated compared with the APAP group. In contrast, a significant decrease in levels of the lipid peroxidation product malondialdehyde was observed in the ginsenoside Rk1-treated group compared with the APAP group. These effects were associated with a significant increase of cytochrome P450 E1 and 4-hydroxynonenal levels in liver tissues. Moreover, ginsenoside Rk1 supplementation suppressed activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels, which was shown using western blotting analysis. Histopathological observation also revealed that ginsenoside Rk1 pretreatment significantly reversed APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress, such as 3-nitrotyrosine, were also inhibited after pretreatment with Rk1 compared with the APAP group. Conclusion: The results clearly suggest that the underlying molecular mechanisms in the hepatoprotection of ginsenoside Rk1 in APAP-induced hepatotoxicity may be due to its antioxidation, antiapoptosis, anti-inflammation, and antinitrative effects.

• BMB Reports
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• v.52 no.3
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• pp.190-195
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• 2019

Acetaminophen (APAP) overdose can cause hepatotoxicity by inducing mitochondrial damage and subsequent necrosis in hepatocytes. Sirtuin2 (Sirt2) is an $NAD^+$-dependent deacetylase that regulates several biological processes, including hepatic gluconeogenesis, as well as inflammatory pathways. We show that APAP decreases the expression of Sirt2. Moreover, the ablation of Sirt2 attenuates APAP-induced liver injuries, such as oxidative stress and mitochondrial damage in hepatocytes. We found that Sirt2 deficiency alleviates the APAP-mediated endoplasmic reticulum (ER) stress and phosphorylation of the p70 ribosomal S6 kinase 1 (S6K1). Moreover, Sirt2 interacts with and deacetylates S6K1, followed by S6K1 phosphorylation induction. This study elucidates the molecular mechanisms underlying the protective role of Sirt2 inactivation in APAP-induced liver injuries.

• Herbal Formula Science
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• v.28 no.1
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• pp.1-13
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• 2020

Objectives : Present study investigated hepatoprotective effects of four types of Taraxaci Herba water extract (TL-F, Taraxaci Herba leaf originated from foreign country; TR-F, Taraxaci Herba root originated from foreign country; TL-K, Taraxaci Herba leaf originated from Korea; TR-K, Taraxaci Herba root originated from Korea) on carbon tetrachloride (CCl₄)-induced acute liver injury. Methods : Mice were administered orally with 200 mg/kg of TL-F, TR-F, TL-K, or TR-K for seven days, and intraperitoneally injected with 0.5 mL/kg of CCl₄ 1 h after last Taraxaci Herba treatment. Silymarin (100 mg/kg) was used as a positive drug. Body weight gain, relative liver weight, serum biochemistry, histopathological and immunohistochemical analyses, and hepatic antioxidant capacity were determined to investigate the hepatoprotective effect of four extracts. Results : Administration of four types of Taraxaci Herba extract increased body weight gain, and decreased relative liver weight in CCl₄-injected mice. As compared to CCl₄ group, TL-F and TR-F significantly decreased serum aspartate aminotransferase activity, while four extracts reduced CCl₄-induced alanine aminotransferase activity. In addition, TL-F and TR-F significantly decreased the numbers of degenerated hepatocytes, infiltrated inflammatory cells, cleaved caspase-3 positive cells, and cleaved PARP positive cells in hepatic tissues. Moreover, TL-F, TR-F, and TR-K administration reduced the lipid peroxidation and nitrotyrosine, and increased glutathione, superoxide dismutase, and catalase activities in hepatic tissues. There were no statistical differences between TL-F- and silymarin-treated group. Conclusion : Of four extracts tested, present results suggest that TL-F is the most favorable candidate against CCl₄-induced acute liver injury through enhancing antioxidant activity.

• The Korea Journal of Herbology
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• v.33 no.1
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• pp.47-55
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• 2018

Objectives : The current study is to evaluate the hepatoprotective effect of youngyanggak-san (YGS) on thioacetamide (TAA)-induced acute liver injury in rats. Methods : YGS is composed of Glycyrrhizae Radix, Asiasari Radix, Cimicifugae Rhizoma, Saigae Tataricae Cornu. While N-YGS (non-youngyanggak-san) doesn't include Saigae Tataricae Cornu. Two samples were administrated TAA together for 3 days. Thirty-six rats were divided into four groups. Rats except for the normal group were received TAA (200 mg/kg of body weight, I.P) were divided into three groups (n=9/group) : Group 1 (TAA only), Group 2 (TAA + 200 mg/kg YGS) and Group 3 (TAA + 200 mg/kg N-YGS). Acute liver damage confirmed using histological examination, The factors associated with oxidative stress and liver function activity measured in serum. Also, expressions of inflammation related proteins were investigated by western blot analysis. Results : Oxidative stress factors such as ROS and $ONOO^-$ in the Group 2 was manifested by a significant rise compared with Group 1. YGS markedly decreased the elevated ROS and $ONOO^-$. Furthermore, YGS significantly reduced the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) The nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) activation induced by TAA led to increase both inflammatory mediators and cytokines. While YGS administration remarkably suppressed such the overexpression. In addition, the histopathological analysis showed that the liver tissue lesions were improved obviously in YGS treatment. Conclusion : YGS provided a hepatoprotective effect on acute liver damage through the suppression of oxidative stress. Especially, this effect enhanced markedly when Saigae Tataricae Cornu is included.

• Herbal Formula Science
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• v.31 no.2
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• pp.111-124
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• 2023

Objectives : Oxidative stress is an important cause of many diseases including liver injury. Therefore, adequate regulation of oxidative stress plays a pivotal role in maintaining liver function. Until recently, there has been no studies on the hepatoprotective effect of Samchulgeonbi-tang (SCGBT). Therefore, the hepatoprotective effect of SCGBT was investigated in HepG2 cells. In this study, oxidative stress was induced by arachidonic acid (AA) and iron. Methods : To analyze the hepatoprotective effects of SCGBT against oxidative stress induced by AA + iron, the cell viability, apoptosis-related proteins and intracellular ROS, glutathione (GSH), and mitochondrial membrane permeability (MMP) were measured. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) transcription activation and expressions of Nrf2 target gene were analyzed through immunoblot analysis. Results : SCGBT increased the cell viability from AA + iron - induced cell death and inhibited apoptosis by regulating apoptosis related proteins. SCGBT protected cells by inhibiting ROS production, GSH depletion, and MMP degradation against AA + iron induced oxidative stress. Furthermore, Nrf2 activation was increased by SCGBT, and the Nrf2 target genes were also activated by SCGBT. Conclusions : These results suggest that the SCGBT has a hepatocyte protection effect and antioxidant effect from AA + iron induced oxidative stress.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.400-407
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• 2023

Background: Rb3 is a ginsenoside with anti-inflammatory properties in many cell types and has been reported to attenuate inflammation-related metabolic diseases such as insulin resistance, nonalcoholic fatty liver disease, and cardiovascular disease. However, the effect of Rb3 on podocyte apoptosis under hyperlipidemic conditions, which contributes to the development of obesity-mediated renal disease, remains unclear. In the current study, we aimed to investigate the effect of Rb3 on podocyte apoptosis in the presence of palmitate and explore its underlying molecular mechanisms. Methods: Human podocytes (CIHP-1 cells) were exposed to Rb3 in the presence of palmitate as a model of hyperlipidemia. Cell viability was assessed by MTT assay. The effects of Rb3 on the expression of various proteins were analyzed by Western blotting. Apoptosis levels were determined by MTT assay, caspase 3 activity assay, and cleaved caspase 3 expression. Results: We found that Rb3 treatment alleviated the impairment of cell viability and increased caspase 3 activity as well as inflammatory markers in palmitate-treated podocytes. Treatment with Rb3 dosedependently increased PPARδ and SIRT6 expression. Knockdown of PPARδ or SIRT6 reduced the effects of Rb3 on apoptosis as well as inflammation and oxidative stress in cultured podocytes. Conclusions: The current results suggest that Rb3 alleviates inflammation and oxidative stress via PPARδ-or SIRT6-mediated signaling, thereby attenuating apoptosis in podocytes in the presence of palmitate. The present study provides Rb3 as an effective strategy for treating obesity-mediated renal injury.

• CELLMED
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• v.8 no.3
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• pp.12.1-12.7
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• 2018

The study was designed to assess antioxidant and antidyslipidaemic effects of terpenoid-rich extract from the root of Aristolochia ringens V. Hyperglycemia-induced oxidative stress and dyslipidemia were established in rats by single intraperitoneal administration of 65 mg/kg bw streptozotocin. Based on therapeutic dose determined in previous study, streptozotocin-induced rats were orally administered with 75 and 150 mg/Kg bw of A. ringens extract for 14 days. Total protein, serum lipid profiles and biomarkers of oxidative stress in liver and kidney of the experimental rats were determined. Atherogenic and cardiovascular disease risk indices were computed. Streptozotocin-induced hyperglycaemia significantly (p < 0.05) decreased activities of superoxide dismutase, catalase and glutathione transferase as well as the amount of reduced glutathione in both tissues indicating oxidative stress induced kidney and liver injury due to glucotoxicity. In comparison to non-treated hyperglycaemic rats, activities of the antioxidant enzymes and concentration of glutathione-H were significantly (p < 0.0001) increased, whereas malondialdehyde was reduced in the tissues of rats treated with both 75 and 150 mg/Kg bw of the extract. The extract also caused significant (p < 0.001) reduction in elevated levels of total cholesterol, triglycerides and low density lipoprotein-cholesterol levels, whereas concentration of the attenuated high density lipoprotein-cholesterol was increased in serum of the treated rats. Reduced atherogenic and cardiac risk indices were projected for the A. ringens extract-treated groups. Results from this study showed that extract from A. ringens root was rich in terpenoids and may reduce risks of complications associated with hyperglycemia-induced oxidative stress and dyslipidemia.