Inhibition of Concanavalin A-Induced Mice Hepatitis by Coumarin Derivatives

T, Okamoto; Yoshida, Shigeaki; Kobayashi, Tadashi; Okabe, Susumu

doi:10.1254/jjp.85.95

Cited by 45 publications

(41 citation statements)

References 11 publications

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“…Osthole has long been used for the treatment of eczema, cutaneous pruritus, trichomonas vaginalis infection, and sexual dysfunction. Recent studies have revealed that Osthole may have anti-inflammatory [6], vasorelaxant [7], and antiallergic [8] effects, as well as the prophylactic effects in hepatitis [9]. In addition, Osthole, as widely reported, exhibits an anti-cancer effect by suppressing cancer cell growth and enhancing apoptosis [10,11,12,13,14].…”

Section: Introductionmentioning

confidence: 99%

Osthole Exhibits Anti-Cancer Property in Rat Glioma Cells Through Inhibiting PI3K/Akt and MAPK Signaling Pathways

Ding

Wei

Song

et al. 2013

Cell Physiol Biochem

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Aims: The purpose of this study was to investigate how Osthole affects glioma cell proliferation, apoptosis, invasion and migration. Methods: Rat glioma cells were treated with different concentrations of Osthole (0 µM, 25 µM, 50 µM, and 100 µM). Cell proliferation was assessed by measuring PCNA expression and CCK8 assay at different time points. Apoptosis was evaluated by measuring the expression of pro-apoptotic protein including Bax, Bcl2, PARP, and cleaved Caspase3, and of anti-apoptotic protein Survivin. Cell migration and invasion were assessed using different methods. Signaling pathways such as PI3K/Akt and MAPK, which are involved in the development of glioma cells, were also investigated in this study. Results: Treatment with Osthole markedly inhibits glioma cell proliferation, as assessed by western blot with the PCNA antibody. Osthole also induces cell apoptosis by upregulating the expression of pro-apoptotic proteins, and by reducing the expression of anti-apoptotic factors. Moreover, C6 cell migration and invasion were efficiently inhibited in groups treated with Osthole, compared to the control group. Additionally, inhibition of PI3K/Akt and MAPK signaling pathway was also observed in C6 cells treated with Osthole. Conclusions: Our findings showed an anti-cancer effect of Osthole on glioma cells, including the proliferation inhibition, apoptosis induction, and migration/invasion inhibition. Further investigation in C6 glioma cells implicated the role of Osthole in essential pathways controlling glioma cell progression. Taken together, our data suggested that Osthole may have a potential application in glioma therapy.

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Section: Introductionmentioning

confidence: 99%

Osthole Exhibits Anti-Cancer Property in Rat Glioma Cells Through Inhibiting PI3K/Akt and MAPK Signaling Pathways

Ding

Wei

Song

et al. 2013

Cell Physiol Biochem

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“…Coumarin derivatives are active components of herbal medicine and are known not to exhibit cellular toxicity. In the present study, the coumarins' doses were arranged according to the previous studies [32,38]. Direct evidence of oxidative stress was noted in the occurrence of alterations in various hepatic parameters decreased activities of antioxidant enzymes CAT, SOD and increased MDA levels in CCl 4 applied group in comparison to control.…”

Section: Discussionmentioning

confidence: 91%

The hepatoprotective effect of coumarin and coumarin derivates on carbon tetrachloride-induced hepatic injury by antioxidative activities in rats

et al. 2011

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Coumarins are a vast group of natural compounds and some of them possess antioxidant activities. The comparison of the antioxidant activity of some coumarins with various chemical molecular structure has not been investigated in previous studies. Therefore, this study was aimed to investigate the hepatoprotective effect against carbon tetrachloride (CCl(4)) -induced hepatic injury by coumarin (1,2-benzopyrone) and coumarin derivatives, esculetin (6,7-dihydroxycoumarin), scoparone (6,7-dimethoxycoumarin), and 4-methylumbelliferone (7-hyroxy-4-methyl) in male Sprague-Dawley rats. Product of lipid peroxidation, malondialdehyde (MDA), activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) were evaluated for oxidative stress in hepatic injury. Gamma glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) were detected in plasma as a biomarker of hepatic injury. Significantly elevated levels of MDA and lowered levels of SOD and CAT activities were observed in liver of rats exposed to CCl(4), when compared to control values. Similarly, administration of CCl(4) increased LDH and GGT levels in serum. Pre-treatment of rats with esculetin (35 mg kg(-1), orally) and scoparone (35 mg kg(-1), orally) significantly prevented CCl(4)-induced decrease in MDA levels and increase in SOD and CAT, whereas 4-methylumbelliferone (35 mg kg(-1)) and coumarin (30 mg kg(-1)) had no effect against CCl(4)-induced rise in serum enzymes. Esculetin and scoparone also showed protective properties as was evidenced in reduced LDH and GGT levels in serum. The results of this study indicate that the chemical structures of coumarins play an important role in the prevention of oxidative stress.

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“…In Con A-induced hepatitis, osthole, imperatorin, pd-Ia, pd-II and pd-III show stronger effects than glycyrrhizin to decrease Con A-induced elevation of plasma ALT. Furthermore, a morphological study also showed the effectiveness of these coumarins (not shown) (18). Of these coumarins, osthole and imperatorin have the strongest protective effects.…”

Section: Coumarinsmentioning

confidence: 94%

“…Of these coumarins, osthole and imperatorin have the strongest protective effects. Osthenol is an osthole derivative with substitution of a 7-methoxy group for the 7-hydroxy of osthole, whereby it loses its protective effect (18). Thus, the 7-methoxy group of osthole plays an important role in protecting the liver against injury.…”

Section: Coumarinsmentioning

confidence: 99%

“…Thus, the 7-methoxy group of osthole plays an important role in protecting the liver against injury. Furthermore, osthole, even at the dose of 200 mg/ kg, has a minimal effect on Con A-induced gene expression of cytokines such as TNF-= and IL-2 (18). Blockade of Ca 2+ channels or phosphodiesterases (19) might be involved in the protective effect of coumarins on liver injury.…”

Section: Coumarinsmentioning

confidence: 99%

See 1 more Smart Citation

Hepatoprotective Drugs for the Treatment of Virus-Induced Chronic Hepatitis: From Hypercarcinogenic State to Hypocarcinogenic State

Okamoto

Kajino

Hino

2001

Japanese Journal of Pharmacology

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ABSTRACT-Interferon (IFN)-based therapy is a standard treatment for chronic hepatitis caused by hepatitis C virus (HCV) infection. This treatment is effective in approximately 30 -40% of the patients and using ribavirin in combination with IFN increases the rate of sustained virologic clearance. For the remaining patients, glycyrrhizin is often used. Glycyrrhizin is known to prevent the development of hepatocellular carcinoma (HCC), but glycyrrhizin is usually administered intravenously. Drugs that are effective by oral administration are convenient for patients for long-term administration, and development of more effective drugs than glycyrrhizin is preferable. However, studies on drugs for the treatment of hepatitis are not actively conducted, and promotion of the study of drugs in this area is encouraging. For that reason, we show our approach to study drugs for the treatment of hepatitis. We analyzed the effect of glycyrrhizin on hepatitis as a standard chemical using the mouse liver injury model. Based on this, we screened drugs and found that a coumarin derivative seems to be one of model chemicals for the treatment of hepatitis.

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Inhibition of Concanavalin A-Induced Mice Hepatitis by Coumarin Derivatives

Cited by 45 publications

References 11 publications

Osthole Exhibits Anti-Cancer Property in Rat Glioma Cells Through Inhibiting PI3K/Akt and MAPK Signaling Pathways

Osthole Exhibits Anti-Cancer Property in Rat Glioma Cells Through Inhibiting PI3K/Akt and MAPK Signaling Pathways

The hepatoprotective effect of coumarin and coumarin derivates on carbon tetrachloride-induced hepatic injury by antioxidative activities in rats

Hepatoprotective Drugs for the Treatment of Virus-Induced Chronic Hepatitis: From Hypercarcinogenic State to Hypocarcinogenic State

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