• BMB Reports
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• 제48권5호
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• pp.289-294
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• 2015

Caesalpinia sappan is a well-distributed plant that is cultivated in Southeast Asia, Africa, and the Americas. C. sappan has been used in Asian folk medicine and its extract has been shown to have pharmacological effects. Two homoisoflavonoids, sappanol and brazilin, were isolated from C. sappan by using centrifugal partition chromatography (CPC), and tested for protective effects against retinal cell death. The isolated homoisoflavonoids produced approximately 20-fold inhibition of N-retinylidene-N-retinyl-ethanolamine (A2E) photooxidation in a dose-dependent manner. Of the 2 compounds, brazilin showed better inhibition (197.93 ± 1.59 μM of IC₅₀). Cell viability tests and PI/Hoechst 33342 double staining method indicated that compared to the negative control, sappanol significantly attenuated H₂O₂-induced retinal death. The compounds significantly blunted the up-regulation of intracellular reactive oxygen species (ROS), and sappanol inhibited lipid peroxidation in a concentration-dependent manner. Thus, both compounds represent potential antioxidant treatments for retinal diseases. [BMB Reports 2015; 48(5): 289-294]

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2753-2758
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• 2012

Rubia cordifolia Linn, which belongs to the Rubiaceae family, is a well-known herb used in Ayurvedic medicine. In the present study, we investigated the influence of a methanolic extract (RC) on the induction of apoptosis in HEp-2 (human laryngeal carcinoma) cell line, as evidenced by cytotoxicity, morphological changes and modification in the levels of pro-oxidants. Inhibition of cell proliferation and lactate dehydrogenase (LDH) release increased in a time and dose-dependent manner. Further, reduced glutathione (GSH), glutathione transferase (GST) and protein levels decreased and lipid peroxidation increased significantly on RC treatment in a dose dependent manner when compared to controls. Based on the results we determined the optimal dose as 30mg/ ml and the apoptotic effect of RC extract (30 mg/ml) on HEp-2 cells was confirmed by fluorescent microscopy and transmission electron microscopy (TEM) based on morphological and ultrastructural changes. RC extract suppressed the proliferation of HEp-2 oral cancer cells inducing apoptotic cell death in vitro. These results point to potential of RC extract as an agent for the treatment of laryngeal squamous cell carcinoma.

• Toxicological Research
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• 제33권3호
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• pp.219-224
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• 2017

Lipin1 was identified as a phosphatidate phosphatase enzyme, and it plays a key role in lipid metabolism. Since free radicals contribute to metabolic diseases in the liver, this study investigated the effects of free radicals on the regulation of Lipin1 expression in Huh7 and AML12 cells. Hydrogen peroxide induced mRNA and protein expression of Lipin1 in Huh7 cells, which was assayed by quantitative RT-PCR and immunoblotting, respectively. Induction of Lipin1 by hydrogen peroxide was confirmed in AML12 cells. Hydrogen peroxide treatment significantly increased expression of sterol regulatory element-binding protein (SREBP)-2, but not SREBP-1. Moreover, nuclear translocation of SREBP-2 was detected after hydrogen peroxide treatment. Hydrogen peroxide-induced Lipin1 or SREBP-2 expression was significantly reduced by N-acetyl-$\small{L}$-cysteine treatment, indicating that reactive oxygen species (ROS) were implicated in Lipin1 expression. Next, we investigated whether the hypoxic environments that cause endogenous ROS production in mitochondria in metabolic diseases affect the expression of Lipin1. Exposure to hypoxia also increased Lipin1 expression. In contrast, pretreatment with antioxidants attenuated hypoxia-induced Lipin1 expression. Collectively, our results show that ROS activate SREBP-2, which induces Lipin1 expression.

• 대한약리학회지
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• 제32권3호
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• pp.389-397
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• 1996

위점막은 위강내에서 생성되는 독성이 강한 활성산소종에 노출된다. Nitric oxide는 glutathione의 항상성을 유지시킴으로써 acetaminophen 유도 간독성에 대한 보호효과를 나타내었다. 본 연구는 hydrogen peroxide로 인한 위선세포 손상에 대한 nitric oxide의 작용을 규명하고자 하였다. Hydrogen peroxide는 ${\beta}-D-glucose$와 glucose oxidase의 반응에 의해 생성시켰으며, 위선세포에 L-arginine, $N^{G}-nitro-L-arginine$ methyl ester 및 $N^G-nitro-L-arginine$을 전처리 한 후, 세포외로 유리되는 지질과산화물 및 nitrite를 정량하고 세포내 glutathione 함량을 측정하였다. 결과로서, glucose/glucose oxidase를 처리한 경우 glucose oxidase 농도의존적으로 지질과산화물 생성은 증가되었으며, nitrite 유리 및 glutathione 함량은 감소되었다. NO synthase의 기질인 L-arginine 전처리시 glucose/glucose oxidase에 의한 지질과산화 및 nitrite 유리 증가와 세포내 glutathione 감소등이 방지되었다. $N^G-nitro-L-arginine$ methyl ester 및 $N^G-nitro-L-arginine$등 NO synthase 억제제들은 세포손상에 보호효과를 나타내지 않았다. 결론적으로 nitric oxide는 hydrogen peroxide로 인한 세포손상에 대한 보호효과가 없으며, 이는 지질과산화 반응 및 세포내 glutathione 고갈등을 억제시킴으로써 이루어진다고 사료된다.

• Preventive Nutrition and Food Science
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• 제18권1호
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• pp.11-17
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• 2013

Dysfunction of endothelial cells is considered a major cause of vascular complications in diabetes. In the present study, we investigated the protective effect of Padina arborescens extract against high glucose-induced oxidative damage in human umbilical vein endothelial cells (HUVECs). High-concentration of glucose (30 mM) treatment induced cytotoxicity whereas Padina arborescens extract protected the cells from high glucose-induced damage and significantly restored cell viability. In addition, lipid peroxidation, intracellular reactive oxygen species (ROS), and nitric oxide (NO) levels induced by high glucose treatment were effectively inhibited by treatment of Padina arborescens extract in a dose-dependent manner. High glucose treatment also induced the overexpressions of inducible nitric oxide synthase (iNOS), cyclooxygenase- 2 (COX-2) and NF-${\kappa}B$ proteins in HUVECs, but Padina arborescens extract treatment reduced the over-expressions of these proteins. These findings indicate the potential benefits of Padina arborescens extract as a valuable source in reducing the oxidative damage induced by high glucose.

• 대한약리학회지
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• 제27권1호
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• pp.69-80
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• 1991

Iron(II)에 의한 마이크로좀의 지질 과산화에 미치는 quercetin과 rutin의 억제 효과를 iron의 산화중에서 생성되는 산소 라디칼에 대한 제거 작용과 iron에 대한 킬레이트 작용에 관하여 관찰하였다. $Fe^{2+}$ 단독에 의한 지질 과산화는 quercetin 또는 rutin에 의하여 용량에 따라 현저하게 억제되었다. $Fe^{2+}$의 존재하에서 ascorbate또는 NADPH에 의한 지질 과산화는 quercetin과 rutin에 의하여 거의 완전히 억제되었다. $Fe^{2+}$의 과산화 작용은 SOD와 DABCO에 의하여 억제되었고 catalase, DMSO와 mannitol에 의하여 약간 억제되었다. Quercetin과 rutin은 DETAPAC에 반응하는 $Fe^{2+}$의 산화를 억제하였고 반응초기에 유의한 킬레이트 효과를 나타내었다. Quercetin과 rutin은 효과적으로 $H_{2}O_{2}$에 의한 지질 과산화를 억제하였으며 $H_{2}O_{2}$를 분해하였다. $Fe^{2+}$의 존재하에서 $OH{\cdot}$의 생성과 U.V. 조사에 의한 $^1O_2$의 생성은 모두 quercetin과 rutin에 의하여 억제되었다. $Cd^{2+},\;Cu^{2+},\;Ni^{2+},\;Pb^{2+}$와 $Zn^{2+}$에 의한 지질 과산화는 quercetin에 의하여 거의 완전하게 억제 되었다. Quercetin과 rutin은 $Fe^{2+}$에 의한 sulfhydryl기의 손실을 유의하게 저해 하였다. 이상의 결과로부터 ascorbate와 NADPH가 있거나 없는 상태에서 $Fe^{2+}$의 과산화 작용에 대한 quercetin과 rutin의 억제 효과는 그들의 반응성 산소 대사물에 대한 제거 작용과 iron에 대한 킬레이트 작용에 기인하였을 것으로 시사된다.

• 동국한의학연구소논문집
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• 제7권1호
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• pp.87-98
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• 1998

백강잠 추출물이 신장조직에서 반응성 산소기들에 의한 지질의 과산화와 세포 손상을 방지하는지를 관찰하기 위하여 정상조직과 t-BHP를 처리한 조직에서 백강잠 추출물의 효과를 조사하였다. 지질의 과산화와 LDH 유출은 t-BHP의 농도에 비례하여 증가되었으나, 백강잠 추출물의 첨가로 유의하게 억제되었다. 그리고, t-BHP에 의한 지질의 과산화 및 LDH 유출은 백강잠 추출물의 농도에 비례하여 억제되었다. 또한, 백강잠 추출물은 oxidant를 처리하지 않은 정상조직에서도 지질의 과산화 및 LDH 유출을 유의성 있게 감소시켰다. 그리고, catalase 활성에는 영향이 없는 반면, 정상 조직과 t-BHP를 처리한 조직에서는 glutathione peroxidase 활성을 유의성 있게 증가시켰다. 한편, 반응성 산소기의 발생은 백강잠 추출물의 농도에 비례하여 억제되었다. 이러한 결과로 볼 때, 백강잠 추출물은 신장 조직내 항산화 효소의 활성을 증가시킴과 동시에 직접 반응성 산소기의 발생을 억제하므로 신장 조직에서 지질의 과산화와 세포손상을 방지하는 효과가 있을 것으로 여겨진다.

• 동의신경정신과학회지
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• 제19권3호
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• pp.129-142
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• 2008

Objective: The purpose of this study was to evaluate the antioxidative effects of the extract of Scolopendra subspinipes which has been used mainly for detoxication in the oriental medicine and reported to have sedative action, antiinflammatory effect, antihypertensive property and immunity enhancing activity. Method: Inhibitory activities on oxygen radical generating enzymes (aldehyde oxidase and xanthine oxidase) and increasing activities on oxygen radical scavenging enzymes (superoxide dismutase, glutathione peroxidase, glutathione-S-transferase) were investigated. Furthermore, the content of glutathione in the mouse brain, DPPH radical scavenging activity and also anti-lipid peroxidative effects in vivo and in vitro were estimated. Results: The extract showed weak inhibitory effects on the activities of aldehyde oxidase and xanthine oxidase which are oxygen radical generating enzymes. The extract inhibited lipid peroxidation with 26.1% against control group at 500 mg/kg in vivo and with 11.2% against control group at 10 mg/kg in vitro in a dose-dependent manner, which means this drug may protect radical-induced cell damages. The extract showed dose-dependently the scavenging effect on DPPH radical with 24.8% activity at 10 mg/ml in vitro. The extract enhanced the activities of superoxide dismutase, glutathione peroxidase and glutathione-S-transferase, which are oxygen radical scavenging enzymes, with 28.9%, 22.3% and 23.1%, respectively at 500mg/kg in vivo. Finally, this extract strongly increased the glutathione content in the mouse barin. Conclusion: Above results indicated that Scolopendra subspinipes can be useful for the protection or treatment of some diseases caused by reactive oxygen species.

• Biomolecules & Therapeutics
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• 제17권3호
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• pp.318-324
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• 2009

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has recently been synthesized and characterized to have an anti-inflammatory activity through the inhibition of the production of nitric oxide. In the present study, adverse effects of FPP-3 on hepatic functions were determined in female BALB/c mice. When mice were administered with FPP-3 at 125, 250 or 500 mg/kg for 7 consecutive days orally, FPP-3 significantly increased absolute and relative weights of liver with a dose-dependent manner. In addition, FPP-3 administration dramatically increased the hepatotoxicity parameters in serum at 500 mg/kg, in association of hepatic necrosis. FPP-3 significantly induced several phase I enzyme activities. To elucidate the possible mechanism(s) involved in FPP-3 induced hepatotoxicity, we investigated the hepatic activities of free radical generating and scavenging enzymes and the level of hepatic lipid peroxidation. FPP-3 treatment significantly elevated the hepatic lipid peroxidation, measured as the thiobarbituric acid-reactive substance, and the activity of superoxide dismutase. Taken together, the present data indicated that reactive oxygen species might be involved in FPP-3-induced hepatotoxicity.

• 동의생리병리학회지
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• 제31권3호
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• pp.159-166
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• 2017

Through this study, the authors investigated the anti-steatosis effects of the Amomum cardamomum ethyl acetate fraction in free fatty acids (FFAs)-induced human hepatocellular carcinoma HepG2 cells. The ethyl acetate fraction of Amomum cardamomum (ACEA) was extracted with 70% ethanol and then the extract was evaporated using a rotary evaporator prior to sequential fractionation. Human hepatocellular carcinoma were treated with different concentrations of ACEA in the presence and absence of FFAs. To demonstrate the reactive oxygen species (ROS) scavenging activity, DCFDA level was analyzed by using in vitro assay system. Cell viability, lipid accumulation, intracellular triglycerides, malondialdehyde (MDA), liver steatosis related signaling molecules and inflammatory cytokines such as interleukin (IL)-6, 8, tumor necrosis factor-alpha ($TNF-{\alpha}$) were also investigated. As results, ACEA inhibited the FFAs-induced ROS, lipid accumulation, intracellular triglycerides, and MDA in a dose dependent manner. Treatment of human hepatocellular cells with ACEA induced the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK) and carnitine palmitoyltransferase I (CPT1) expression using western blot analysis. ACEA also potently suppressed the FFAs-induced inflammatory cytokines including IL-6, IL-8 and $TNF-{\alpha}$. These results suggest that the ethyl acetate fraction of Amomum cardamoum extract own inhibitory effects of liver steatosis by inhibiting ROS, lipid accumulation, intracellular triglycerides, MDA through AMPK signaling and anti-inflammatory actions.