Thermodynamic parameters for the hydrogen bonding between thiopropionamide(TPA) and proton donors such as triethylphosphine oxide(TEPO), triphenylphosphine oxide(TPPO), trimethylphosphate(TMP), and tributyl phosphate(TBP) in dilute carbon tetrachloride solution have been measured by near-IR spectroscopy. The νa + amide Ⅱ combination band of TPA has been resolved into two Lorentzian-Gaussian product components which have been identified with monomeric TPA and 1 : 1 hydrogen bonded complex. The equilibrium constants and thermodynamic parameters for the formation of 1 : 1 hydrogen bonded complex have been obtained by the analysis of concentration and temperature dependent spectra. The standard enthalpies for the 1 : 1 hydrogen bonded complex formation of TPA with TEPO, TPPO, TMP, and TBP in CCl4 have been found to be - 21.4, - 16.8, - 12.8, and - 12.9 kJ/mol, respectively. The results are explained by the inductive and steric effects of substituents.
Root extract of Lythrum salicaria reported a hepato-protective effect on $CCl_4$-induced liver toxicity of rat was prepared into fractions such as n-hexane up layer (HA), n-hexane down layer (HB), diethyl ether (E), ethylacetate (EA), n-butanol (B) and water (W). Fractions prepared were tested their activities in vitro and in vivo condition. All of the fractions showed effective antioxidant asctivities on DPPH radical and $CuSO_4$-induced oxidation of human low density lipoprotein and E fraction showed the highest inhibitory effect (98.1% at $50\;{\mu}g/m{\ell}$) on linoleic acid autoxidation at $40^{\circ}C$, which was more effective than $\alpha$-tocopherol (82.4%). Five fractions (H = HA plus HB, E, EA, B, and W, 150 mg/kg/day) were fed into Sprague Dawley, male rats for 4 days, which were intoxicated with intra-peritoneal injection of carbon tetrachloride ($1\;m{\ell}/kg$ in corn oil) at the 4th day and were sacrificed in 24 hrs. Serum tumor necrosis factor-alpha (TNF-$\alpha$), a proinflammatory cytokine, elevated with $CCl_4$-intoxication in negative control group ($83\;pg/m{\ell}$) was significantly decreased in E fraction-supplemented group ($18\;pg/m{\ell}$). Cu, Zn-superoxide dismutase (SOD) activity increased in negative control group (0.12 U/mg protein) was decreased in E fraction (0.07 U/mg protein). From the results, it is suggested that ether fraction from root extract of L. salicaria would be a potent antioxidant candidate for ameliorating liver injury induced by chemical intoxicant.
This study was carried out to investigate antioxidative, antimicrobial activity and the effect on hepatotoxicity in various extracts of Artemisia iwayomogi. The herb has been used widely for jaundice, hepatitis and liver cirrhosis in chinese medicine. Solid yield by various extraction solvents, 18.1%, was the highest in water extract. To find antioxidative activity in Artemisia iwayomogi was estimated radical scavenging effect by DPPH method in various extracts and change of the POV(peroxide value) of various extracts added in soybean oil during 20 days at $60^{\circ}C$. Radical scavenging effect by DPPH method was the most effective in methanol extract. Added 1,000ppm water extract and methanol extract in soybean oil, the POV of them, 46.8(meq/kg) and 50.8(meq/kg) were lower than that of control, 79.1(meq/kg), during 20 days storage. After antimicrobial activity of various extracts of Artemisia iwayomogi on bacteria was carried out by paper disc method, it found that the ethanol extract was the strongest activity on Vibrio parahaemolyticus. In vivo experiment was to investigate the effect of Artemisia iwayomogi water extract(AIWE) on hepatotoxicity by carbon tetrachloride$(CCl_4)$ in rats. The experiment groups were divided into five groups for recovery(for 3 days) and three groups for protection(for 10 days) in rat liver. The weights and morphological changes of liver and the body weight were examined in each groups. Compared with $CCl_4$ treatment groups$(CCl_4\;only)$, liver and liver/body(%) weights of AIWE pretreatment groups for 3 days and AIWE posttreatment groups for 10 days were declined. In macrography, fibrious exudates and swelling of liver were decreased in AIWE treatment groups. Accumulation of lipid droplets and necrosis of hepatocytes were also decreased in AIWE treatment groups in microscopically. In these results, AIWE seems to enhance hepato-protective and recoverable effect on $CCl_4$ induced hepatotoxicity in rats.
The wild simulated ginseng (WSG) has been effectively used in folk medicine as a remedy against hepatic disease, hypertension and arthritic disease. However, there is still lack of scientific proof about its antioxidant capability. The present study has been conducted to evaluate the protective role of the WSG ethanol extract in the CCl4-induced oxidative stress and resultant hepatic disfunction in ICR mice. The electron donating abilities and IC50 of WSG etnanol extract were 76.86 ${\pm}$ 1.06% and 33.3 ${\mu}g$/mL (that of ascobic acid was 16.5 ${\mu}g$/mL), respectively. Total antioxidant status of WSG extract was 2.13 ${\pm}$ 0.06 mmoL/mg, while the values of ascorbic acid and BHT were 3.63 ${\pm}$ 0.06 and 3.12 ${\pm}$ 0.02, respectively. ICR mice (aged 3weeks) were fed for 4 weeks on AIN-93M diet and had free access to food and water. The animals were divided into three groups: normal group (intraperitoneally (i.p) injected with PBS at 100 ${\mu}L$/mouse), group C; CCl4-induced and without any treatment. (i.p injected only PBS, 100 ${\mu}L$ /mice), group G; CCl4-induced and treated with WSG (i.p injected with 5 mg WSG extract per mouse, suspended in 100 ${\mu}L$ phosphate buffer). After the i.p. injection of WSG or PBS (5 times for 7weeks), all mice were administered CCl4 in olive oil at the last day of the experiment, except for normal group. The normal group was administered only olive oil. Determination of plasma triglyceride, total cholersterol, fasting glucose and GPT activity was performed using automatic blood analyzer. To evaluate the protective effect against the oxidative stress, DNA fragmentation and TBARS were determined in blood leucocytes and RBC and hepatocyte, respectively. Body and organs weights and food intake did not show significant differences among the groups. Blood total cholesterol of group G was similar to that of normal group, which was the lowest in group C. The fasting blood glucose level was the highest in normal group (205.20 ${\pm}$ 135.24), which were decreased in group C (134.2 ${\pm}$ 79.31) and group G (126.48 ${\pm}$ 77.05). TBARS values in a red blood cell and hepatic tisuue homogenate were lower in group G comparing to the group C. DNA% in tail, tail length (TL) and tail moment (TM) of blood leucoocytes showed the highest values in group C (20.11 ${\pm}$ 2.47, 17.36 ${\pm}$ 2.58, 94.11 ${\pm}$ 12.29) and they were significantly diminished in group G (9.63 ${\pm}$ 1.19, 7.04 ${\pm}$ 1.50, 38.64 ${\pm}$ 7.60). In conclusion, wild simulated ginseng might be a protective agent against the oxidative stress.
The $2{\nu}_{C=0}$ + amide III combination band spectrum of acetamide (AA) was obtained in very dilute solutions of AA+lanthanide shift reagents (LSR) in carbon tetrachloride over the range of $15^{\circ}$ to $45^{\circ}C$. It was found that only 1 : 1 AA-LSR complex is formed by the interaction between carbonyl oxygen of AA and central metal ion(Ln(Ⅲ)) in LSR. The thermodynamic parameters for Ln(III)${\cdot}$O=C bond were determined by computer analysis of concentration and temperature dependent spectra. ${\Delta}H^{\circ}$ for the coordination of AA to Eu$(dpm)_3$, Yb$(dpm)_3$, and Pr$(dpm)_3$ have been found to be -39.1, -28.4, and -25.5 kJ/mol, respectively. It has shown that this type of ion-dipole interaction is more than twice stronger compared to the dipole-dipole interaction in the amide linkage, and largely depending on the steric hindrence effect by the bulky dpm groups around central metal ion (Ln(III)) rather than the ionic potential effect of central metal ion itself.
$Nokyangbotang^{TM}$ (NYBT) is a kind of powerful food for health and have been drunk at a oral dose of 80 ml (99.5 mg) three times per day: It has not been well studied about the anti-fatigue and hepatoprotective activity. In this experiments, we evaluated pathophysiologically the effect of NYBT on swimming time in mouse and hepatoprotective activity in rats intoxicated with carbon-tetrachloride. NYBT was nontoxic in orally acute toxicity test ($LD_{50}$, 320 ml/60 kg): a nontoxic food in more four times of one-shoot dosage (80 ml) to human. Weight-loaded forced swimming test was carried out to measure the swimming time of mice with a 4% load of body weight in plastic cylinder (diameter $10{\;}cm{\;}{\times}{\;}height{\;}20{\;}cm$) on water bath at $25^{\circ}C$, and the anti-fatigue activity represented the ratio of swimming time of experimental group to that of control group. NYBT had dose-dependent anti-fatigue activity Mice administered NYBT at a dose of 320 ml/60 kg once daily for 5 days could swim about two times more than control. Hepatoprotective activities of NYBT were examined by the determination of malonedialdehyde (MDA) and pathological survey in liver and liver function test of rat intoxicated with $CCl_4$ at i.m. dose of 2 ml/kg once daily for 7days. NYBT decreased dose-dependently thiobarbituric acid reactive substance: Oral administration of NYBT at a dose of 20 ml/60 kg was $38.51{\;}{\pm}{\;}3.02$ nmol MDA/g of tissue, that of 80 ml/60 kg was $33.76{\;}{\pm}{\;} 1.84$ nmol MDA/g of tissue, and that of 320 ml/60 kg was $32.87{\;}{\pm}{\;}1.90$ nmol MDA/g of tissue as compared with control group ($43.61{\;}{\pm}{\;}2.85$ nmol MDA/g of tissue). All rats administered NYBT at a dose of 320 ml/60 kg were survival as compared with 40% survival of control animals, and GPT activity of rats administered NYBT at a dose of 80 ml/60 kg was decreased as compared with control. In histopathological survey, NYBT improved slightly the fatty changes of hepatocytes around centrilobular area. These results suggest that NYBT has anti-fatigue and hepatoprotective activity in rats and mice.
Chunxue Li ;Yating Zhan ;Rongrong Zhang;Qiqi Tao ;Zhichao Lang ;Jianjian Zheng
Journal of Ginseng Research
/
v.47
no.4
/
pp.515-523
/
2023
Background: 20(S)-protopanaxadiol (PPD), one of the main components of ginseng, has anti-inflammatory, anti-estrogenic, and anti-tumor activities. It is known that activated hepatic stellate cells (HSCs) are the primary producers of extracellular matrix (ECM) in the liver, and the Wnt/β-catenin pathway participates in the activation of HSCs. We aimed to explore whether PPD inhibits liver fibrosis is associated with the Wnt/β-catenin pathway inactivation. Methods: The anti-fibrotic roles of PPD were examined both in vitro and in vivo. We also examined the levels of Wnt inhibitory factor 1 (WIF1), DNA methyltransferase 1 (DNMT1) and WIF1 methylation. Results: PPD obviously ameliorated liver fibrosis in carbon tetrachloride (CCl4)-treated mice and reduced collagen deposition. PPD also suppressed the activation and proliferation of primary HSCs. Notably, PPD inhibited the Wnt/β-catenin pathway, reduced TCF activity, and increased P-β-catenin and GSK-3β levels. Interestingly, WIF1 was found to mediate the inactivation of the Wnt/β-catenin pathway in PPD-treated HSCs. WIF1 silencing suppressed the inhibitory effects of PPD on HSC activation and also restored α-SMA and type I collagen levels. The downregulation of WIF1 expression was associated with the methylation of its promoter. PPD induced WIF1 demethylation and restored WIF1 expression. Further experiments confirmed that DNMT1 overexpression blocked the effects of PPD on WIF1 expression and demethylation and enhanced HSC activation. Conclusion: PPD up-regulates WIF1 levels and impairs Wnt/β-catenin pathway activation via the downregulation of DNMT1-mediated WIF1 methylation, leading to HSC inactivation. Therefore, PPD may be a promising therapeutic drug for patients with liver fibrosis.
Background: Ginsenoside Rg1, a bioactive component of Ginseng, has demonstrated anti-inflammatory, anti-cancer, and hepatoprotective effects. It is known that the epithelial-mesenchymal transition (EMT) plays a key role in the activation of hepatic stellate cells (HSCs). Recently, Rg1 has been shown to reverse liver fibrosis by suppressing EMT, although the mechanism of Rg1-mediated anti-fibrosis effects is still largely unclear. Interestingly, Smad7, a negative regulator of the transforming growth factor β (TGF-β) pathway, is often methylated during liver fibrosis. Whether Smad7 methylation plays a vital role in the effects of Rg1 on liver fibrosis remains unclear. Methods: Anti-fibrosis effects were examined after Rg1 processing in vivo and in vitro. Smad7 expression, Smad7 methylation, and microRNA-152 (miR-152) levels were also analyzed. Results: Rg1 significantly reduced the liver fibrosis caused by carbon tetrachloride, and reduced collagen deposition was also observed. Rg1 also contributed to the suppression of collagenation and HSC reproduction in vitro. Rg1 caused EMT inactivation, reducing Desmin and increasing E-cadherin levels. Notably, the effect of Rg1 on HSC activation was mediated by the TGF-β pathway. Rg1 induced Smad7 expression and demethylation. The over-expression of DNA methyltransferase 1 (DNMT1) blocked the Rg1-mediated inhibition of Smad7 methylation, and miR-152 targeted DNMT1. Further experiments suggested that Rg1 repressed Smad7 methylation via miR-152-mediated DNMT1 inhibition. MiR-152 inhibition reversed the Rg1-induced promotion of Smad7 expression and demethylation. In addition, miR-152 silencing led to the inhibition of the Rg1-induced EMT inactivation. Conclusion: Rg1 inhibits HSC activation by epigenetically modulating Smad7 expression and at least by partly inhibiting EMT.
The present experiment was performed in order to know the therapeutic effect of laserpuncture and aquapuncture with methionine on recovery in artificially induced hepatic damaged rats by carbon tetrachloride. The animals were divided into control, laserpuncture and aquapuncture groups. The changes of serum enzyme activities(ALT and AST), serum total protein contents, protein fractions(ALB and GLB) and A/G ratio were examined before and after application of laserpuncture and aquapuncture. In change of serum ALT activity, recovery with treatment in laser and aquapuncture groups was more rapid than that of control. The significant decreased value was shown on 3rd(P < 0.05) and 7th day(P < 0.01) after treatment in laserpuncture group and on 7th day(P < 0.05) after treatment in aquapuncture group. In addition, significance was detected on 2nd day(P < 0.05) between laserpuncture and aquapuncture groups. In change of serum AST activity, recovery with treatment in laserpuncture and aquapuncture groups was more rapid than that of control. The significant lower values on 7th day(P<0.01) in aquapuncture groups. In addition, significant low value was detected on 7th day(P < 0.05) in aquapuncture group comparing with that of laserpuncture group. The change of serum TP contents showed similar pattern in control, laser and aquapuncture groups. The significances were detected on 7th day(P < 0.05) in both experimental groups. In addition, significant high value was detected on 2nd day(P < 0.05) in laserpuncture group comparing with that of aquapuncture group. The change of serum ALB content with treatment in laser and aquapuncture groups was more rapid than that of control. The significant high value was shown on 2nd(P < 0.01), 5th(P < 0.05) and on 7th day(P < 0.01) in laserpuncture group. In addition, significant high value was detected on 3rd day(P<0.01) only in aquapuncture group comparing with laserpuncture group. The change of serum GLB content showed similar pattern among groups. The significant low values were detected on 2nd day(P < 0.05) in aquapuncture group. In addition significant high value was detected on 5th day(P < 0.01) only in laserpuncture group comparing with that of aquapuncture group. In change of A/G ratio laser and aquapuncture groups showed higher values than that of control. The significant high values were detected on 1st day(P < 0.Of) and 2nd day(P < 0.05) in laserpuncture group, and on 1st day(P < 0.05) and 2nd day(P < 0.01) in aquapuncture group. In addition, significant high value was detected on 5th day(P < 0.05) in aquapuncture group comparing with that of laserpuncture. Considering above findings collectively, it was considered that both laserpuncture and aquapuncture were effective; aquapuncture was more effective than laserpuncture for recovery of hepatic damage.
Journal of the Korean Society of Food Science and Nutrition
/
v.38
no.4
/
pp.430-435
/
2009
The effects of turmeric and fermented turmeric by Bacillus natto on antioxidant activities, liver function recovery of acute hepatotoxicity mice, and serum lipid parameters in high fat diet fed mice were investigated. In the results of antioxidant activity by DPPH method, fermented turmeric had higher antioxidative activity than turmeric. Acute hepatotoxicity was induced by 0.5 mL of carbon tetrachloride ($CCl_4$) per kg of mice. Unlike turmeric, fermented turmeric significantly reduced the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) after 5 days compared to the controls with 0.5% methyl cellulose (p<0.05). In addition, higher recovery of liver damage by $CCl_4$ was observed in mice with fermented turmeric than with turmeric. High fat (20%) diet fed mice were divided into 4 groups to investigate the effects of turmeric and fermented turmeric on serum lipid parameters: C (vehicle), TuL (low dose (80 mg/kg) with turmeric), TuH (high dose (160 mg/kg) with turmeric), FTuL (low dose with fermented turmeric), and FTuH (high dose with fermented turmeric). The levels of LDL-cholesterol and HDL-cholesterol were significantly reduced and increased in FTuL, FTuH and TuH groups compared to the C group, respectively. However, there was no significant change in triglyceride levels by either turmeric or fermented turmeric compared to those by control. Collectively, these results strongly suggest that fermented turmeric by Bacillus natto could be used as a functional food for enhancement of health with better consumer acceptance.
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