• 생약학회지
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• 제54권1호
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• pp.9-15
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• 2023

In the previous study, we reported that cynaroside isolated from Lysimachia christinae methanolic extract had potent neuroprotective activities in neuronal cell death injured by excessive glutamate. In this study, we tried to confirm the neuroprotective activities of cynaroside in glutamate injured HT22 cells and establish mechanisms of neuroprotective action of cynaroside. We employed HT22 cells damaged by glutamate-induced cell death as a bioassay system. Cynaroside decreased reactive oxygen species increased by excessive glutamate treatment in HT22 cells. Also, Ca²⁺ concentration was decreased by cynaroside treatment. Cynaroside restored mitochondrial membrane potential to normal condition. It also increased not only glutathione reductase but also peroxidase to the control level. And it increased amount of glutathione, an endogenous antioxidant. These results suggested that cynaroside isolated from L. christinae showed potent neuroprotective activity through the anti-oxidative pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3797-3803
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• 2016

Cervical cancer is the second most common malignancy in women worldwide and thus one of the leading causes of mortality in women. Lovastatin, a non polar, anticholesterol drug has previously been reported to exert antitumour activity in vitro. In the present study, lovastatin from Aspergillus terreus (KM017963) was purified by adsoprtion chromatography and evaluated for its anticancer and anti-oxidant properties with a human cervical cancer cell line (HeLa). Growth inhibitory and proapoptotic effects of purified lovastatin on HeLa cells were investigated by determining its influence on cell numbers, mitochondrial membrane potential (MMP), DNA fragmentation and antioxidant properties in terms of hydroxy radical scavenging effects as well as levels of total reduced glutathione. Cell cycle analysis by flow cytometry (propidium iodide staining) confirmed induction of apoptotic cell death and revealed cell cycle arrest in the G0/G1 phase. Results of the study give leads for the anticancer effects of lovastatin and its potential usefulness in the chemotherapy of cervical cancer.

• Journal of Radiation Protection and Research
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• 제41권3호
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• pp.206-210
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• 2016

Background: Ionizing radiation causes cellular damage and death through the direct damage and/or indirectly the production of ROS, which induces oxidative stress. This study was designed to evaluate the in vivo radioprotective effects of a bio-active material coated fabric (BMCF) against ${\gamma}$-irradiation-induced cellular damage in Sprague-Dawley (SD) rats. Materials and Methods: Healthy male SD rats wore bio-active material coated (concentrations in 10% and 30%) fabric for 7 days after 3 Gy of ${\gamma}$-irradiation. Radioprotective effects were evaluated by performing various biochemical assays including spleen and thymus index, WBC count, hepatic damage marker enzymes [aspartate transaminase (AST) and alanine transaminase (ALT)] in plasma, liver antioxidant enzymes, and mitochondrial activity in muscle. Results and Discussions: Exposure to ${\gamma}$-irradiation resulted in hepatocellular and immune systemic damage. Gamma-irradiation induced decreases in antioxidant enzymes. However, wearing the BMCF-30% decreased significantly AST and ALT activities in plasma. Furthermore, wearing the BMCF-30% increased SOD (superoxide dismutase) and mitochondrial activity. Conclusion: These results suggest that wearing BMCF offers effective radioprotection against ${\gamma}$-irradiation-induced cellular damage in SD rats.

• Journal of Ginseng Research
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• 제47권2호
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• pp.311-318
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• 2023

Background: The beneficial effects of compound K (CK) on different chronic diseases have been shown to be at least related to antioxidant action. Nevertheless, since its antioxidant activity in human retinal pigment epithelial (RPE) cells is still unknown, here we investigated whether CK alleviates oxidative stress-stimulated damage in RPE ARPE-19 cells. Methods: The cytoprotective consequence of CK in hydrogen peroxide (H₂O₂)-treated cells was evaluated by cell viability, DNA damage, and apoptosis assays. Fluorescence analysis and immunoblotting were performed to investigate the inhibitory action of CK on reactive oxygen species (ROS) production and mitochondrial dysfunction. Results: H₂O₂-promoted cytotoxicity, oxidative stress, DNA damage, mitochondrial impairment, and apoptosis were significantly attenuated by CK in ARPE-19 cells. Furthermore, nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation level and its shuttling to the nucleus were increased, which was correlated with upregulated activation of heme oxygenase-1 (HO-1). However, zinc protoporphyrin, a blocker of HO-1, significantly abrogated the preventive action of CK in H₂O₂-treated ARPE-19 cells. Conclusion: This study indicates that activation of Nrf2/HO-1 signaling by CK plays an important role in rescuing ARPE-19 cells from oxidative cellular damage.

• 대한화장품학회지
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• 제48권1호
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• pp.47-53
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• 2022

본 연구에서는 블랙티에 함유된 고분자 카테킨 성분을 효율적으로 추출할 수 있는 조건을 최적화하였다. 발효도에 따른 고분자 카테킨 함량을 확인하기 위하여 세가지 발효도의 블랙티내 고분자 카테킨 함량을 비교하였다. 발효도가 증가할수록 고분자 카테킨 함량이 증가되며 그중 크기가 가장 큰 데아브론닌(theabrownin) 함량이 크게 증가함을 확인하였다. 또한, 경수인 미네랄 워터를 사용하여 추출시 다른 추출수를 사용했을 때 비해 약 150% 이상 데아브로닌의 추출 햠량이 증가됨을 확인하였다. 최적 조건에서 추출된 블랙티 추출물과 그 추출물내 다량으로 함유된 데아브로닌의 항산화 효능을 ABTS assay를 이용하여 확인하였다. 그 결과, 두 추출물 모두 항산화 효능을 갖고 있으며, IC₅₀ 값이 각각 10.60 ppm, 13.21 ppm으로 확인하였다. 또한, 주요 성분인 데아브로닌의 항염 효능을 확인한 결과 UVB 조사에 의해 증가된 IL-8의 mRNA 발현이 데아브로닌에 의해 농도 의존적으로 억제됨을 확인하였다. 또한, 데아브로닌 10 ppm을 처리하면 UVB 조사에 의해 저하된 미토콘드리아의 기능이 대조군 대비 86 ± 1.9%으로 회복되었다. 따라서, 데아브로닌은 UVB 조사에 의해 유발된 미토콘드리아의 손상을 방지할 수 있음을 확인되었다.

• 한국감성과학회:학술대회논문집
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• 한국감성과학회 2008년도 추계학술대회
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• pp.147-150
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• 2008

Vitamin C ascorbic acid (AA) and dehydroascorbic acid (DHA) as an antioxidant have been shown to have protective effects in experimental neurological disorder models such as stroke, ischemia, and epileptic seizures. The present study was conducted to examine the protective effect of AA and DHA on Kainic acid (KA) neurotoxicity using organotypic hippocampal slice cultures (OHSC). After 12h KA treatment, significant delayed neuronal death was detected in CA3 region, but not in CA1. Intermediate dose of AA and DHA pretreatment significantly prevented cell death and inhibit ROS level, mitochondrial dysfunction and capase-3 activation in CA3 region. In the case of low or high dose, however, AA or DHA pretreatment were not effective. These data suggest that both AA and DHA pretreatment have neuroprotective effects on KA-induced neuronal injury depending on the concentration, by means of inhibition of ROS generation, mitochondrial dysfunction, and caspase-dependent apoptotic pathway.

• Animal cells and systems
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• 제16권1호
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• pp.20-26
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• 2012

Drug-induced parkinsonism has been associated with an increased risk for Parkinson's disease. Antipsychotic drugs have long been known to cause parkinsonian symptoms. However, it remains unclear whether antipsychotics can directly damage the nigrostriatal pathway. In the present study, we investigated the toxicity mechanism of two typical antipsychotics, perphenazine and trifluoperazine, in a human dopaminergic cell line, SH-SY5Y. Perphenazine and trifluoperazine induced mitochondrial damage as evidenced by fragmentation of mitochondria, activation of Bax, cytochrome c release and a decrease in cellular ATP level. In addition, activation of caspase-3 and apoptotic nuclei were observed following the drug treatment. However, pan-caspase inhibitor did not suppress the cell death induced by the antipsychotics, suggesting that the initiated apoptosis was possibly shifted to necrosis upon caspase inhibition. Damaged mitochondria may have induced oxidative stress since the drug-induced cell death was partially suppressed by an antioxidant. Taken together, our results suggest that perphenazine and trifluoperazine can induce apoptotic cell death in a dopaminergic cell line via mitochondrial damage accompanied by oxidative stress.

• Biomolecules & Therapeutics
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• 제30권6호
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• pp.585-592
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• 2022

Treatment of triple-negative breast cancer (TNBC) has been limited due to the lack of molecular targets. In this study, we evaluated the cytotoxicity of hydroxyzine, a histamine H1 receptor antagonist in human triple-negative breast cancer BT-20 and HCC-70 cells. Hydroxyzine inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay showed that hydroxyzine induced apoptosis. The hydroxyzine-induced apoptosis was accompanied down-regulation of cyclins and CDKs, as well as the generation of reactive oxygen species (ROS) without cell cycle arrest. The effect of hydroxyzine on the induction of ROS and apoptosis on TNBC cells was prevented by pre-treatment with ROS scavengers, N-acetyl cysteine or Mito-TEMPO, a mitochondria-targeted antioxidant, indicating that an increase in the generation of ROS mediated the apoptosis induced by hydroxyzine. Western blot analysis showed that hydroxyzine-induced apoptosis was through down-regulation of the phosphorylation of JAK2 and STAT3 by hydroxyzine treatment. In addition, hydroxyzine induced the phosphorylation of JNK and p38 MAPK. Our results indicate that hydroxyzine induced apoptosis via mitochondrial superoxide generation and the suppression of JAK2/STAT3 signaling.

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.692-699
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• 2023

The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2 receptor (DRD2) antagonist in human TNBC BT-549 and CAL-51 cells. Domperidone inhibited cell growth in a dose- and time-dependent manner. The annexin V/propidium iodide staining showed that domperidone induced apoptosis. The domperidone-induced apoptosis was accompanied by the generation of mitochondrial superoxide and the down-regulation of cyclins and CDKs. The apoptotic effect of domperidone on TNBC cells was prevented by pre-treatment with Mito-TEMPO, a mitochondria-specific antioxidant. The prevention of apoptosis with Mito-TEMPO even at concentrations as low as 100 nM, implies that the generation of mitochondrial ROS mediated the domperidone-induced apoptosis. Immunoblot analysis showed that domperidone-induced apoptosis occurred through the down-regulation of the phosphorylation of JAK2 and STAT3. Moreover, domperidone downregulated the levels of D2-like dopamine receptors including DRD2, regardless of their mRNA levels. Our results support further development of DRD2 antagonists as potential therapeutic strategy treating TNBC.

• 대한한의학방제학회지
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• 제21권2호
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• pp.63-71
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• 2013

Objectives : Artemisia princeps is used as moxa in moxibustion and traditional herbal medicine. And its extracts or compounds is known to have an efficacy of antioxidant, anti-diabete, anti-cancer, anti-inflammation and neuroprotection. This study was performed to investigate the cytoprotective effect of Artemisia princeps extract (APE) against arachidonic acid (AA)+iron-induced oxidative stress on HepG2 cell. Methods : The effects of APE on cell viability has been assessed using MTT assay. And flow cytometric analysis was performed to estimate APE's effects on mitochondrial function. To investigate its underlying mechanism, related protein was analysed by using immunoblot analysis. Results : Treatment of APE increased relative cell viability, prevented a decline of B-cell lymphoma-extra large (Bcl-xL) and cleavage of poly(ADP-ribose) polymerase (PARP) and procaspase-3, and also protected mitochondrial membrane permeability (MMP) against oxidative stress induced by AA+iron. In addition, APE treatment increased phosphorylation of AMP-activated protein kinase (AMPK) exerts a cytoprotective effect. Conclusions : This results demonstrate that APE has an ability to activation of AMPK which protects cells from AA+iron-induced oxidative stress and restores MMP.