• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.349-360
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• 2024

Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in Cornus officinalis, is reported to have advantages as a natural compound that prevents various diseases. However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H₂O₂) in murine C2C12 myoblasts. Our results demonstrate that morroniside pretreatment was able to inhibit cytotoxicity while suppressing H₂O₂-induced DNA damage and apoptosis. Morroniside also significantly improved the antioxidant capacity in H₂O₂-challenged C2C12 cells by blocking the production of cellular reactive oxygen species and mitochondrial superoxide and increasing glutathione production. In addition, H₂O₂-induced mitochondrial damage and endoplasmic reticulum (ER) stress were effectively attenuated by morroniside pretreatment, inhibiting cytoplasmic leakage of cytochrome c and expression of ER stress-related proteins. Furthermore, morroniside neutralized H₂O₂-mediated calcium (Ca²⁺) overload in mitochondria and mitigated the expression of calpains, cytosolic Ca²⁺-dependent proteases. Collectively, these findings demonstrate that morroniside protected against mitochondrial impairment and Ca²⁺-mediated ER stress by minimizing oxidative stress, thereby inhibiting H₂O₂-induced cytotoxicity in C2C12 myoblasts.

• Interdisciplinary Bio Central
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• v.1 no.2
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• pp.7.1-7.7
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• 2009

"To be, or not to be?" This question is not only Hamlet's agony but also the dilemma of mitochondria in a cancer cell. Cancer cells have a high glycolysis rate even in the presence of oxygen. This feature of cancer cells is known as the Warburg effect, named for the first scientist to observe it, Otto Warburg, who assumed that because of mitochondrial malfunction, cancer cells had to depend on anaerobic glycolysis to generate ATP. It was demonstrated, however, that cancer cells with intact mitochondria also showed evidence of the Warburg effect. Thus, an alternative explanation was proposed: the Warburg effect helps cancer cells harness additional ATP to meet the high energy demand required for their extraordinary growth while providing a basic building block of metabolites for their proliferation. A third view suggests that the Warburg effect is a defense mechanism, protecting cancer cells from the higher than usual oxidative environment in which they survive. Interestingly, the latter view does not conflict with the high-energy production view, as increased glucose metabolism enables cancer cells to produce larger amounts of both antioxidants to fight oxidative stress and ATP and metabolites for growth. The combination of these two different hypotheses may explain the Warburg effect, but critical questions at the mechanistic level remain to be explored. Cancer shows complex and multi-faceted behaviors. Previously, there has been no overall plan or systematic approach to integrate and interpret the complex signaling in cancer cells. A new paradigm of collaboration and a well-designed systemic approach will supply answers to fill the gaps in current cancer knowledge and will accelerate the discovery of the connections behind the Warburg mystery. An integrated understanding of cancer complexity and tumorigenesis is necessary to expand the frontiers of cancer cell biology.

• The Korea Journal of Herbology
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• v.31 no.4
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• pp.101-109
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• 2016

Objectives : HT070 is a mixture of herbal extracts from root of Scutellaria baicalensis and stem bark of Eleutherococcus senticosus , which have long been used for stroke therapy in traditional Korean Medicine. The purpose of this study was to investigate the neuroprotective effects of HT070 on global cerebral ischemia and its potential mechanisms.Methods : Transient global cerebral ischemia was produced by 10 min of four-vessel occlusion (4-VO) in male Wistar rats. HT070 was administered orally at a dosage of 200 mg/kg twice at 0 and 90 min after reperfusion. Hippocampal neuronal damage was measured 7 days after reperfusion. To explore the potential mechanisms, we used hydrogen peroxide (H₂O₂)-induced rat pheochromocytoma (PC12) cells as an in vitro model. PC12 cells were pretreated with HT070 for 1 h and then exposed to 100 μM H₂O₂ for 6 h in the presence of HT070. Cell viability was measured by MTT assay and the mRNA expression of Bax, Bcl-2, iNOS and COX-2 were measured by quantitative RT-PCR.Results : Oral administration of HT070 at a dose of 200 mg/kg significantly reduced neuronal death in the hippocampal CA1 region by 13.4% as compared to the vehicle-treated group. HT070 increased cell viability, reversed the down-regulated Bcl-2 mRNA level, and suppressed the up-regulated mRNA expressions of Bax, iNOS, and COX-2 in H₂O₂-treated PC12 cells.Conclusions : HT070 protects against delayed neuronal death after global cerebral ischemia and its neuroprotection properties might be attributed to the inhibition of mitochondrial apoptosis and ROS-generating enzymes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.507-516
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• 2004

Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the commom disease in public health service. Although a variety of oriental presciptions in study POD(Polygala tenuifolia extracted from dichlorometan) have been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet fully elucidated. It has been widely believed that AP peptide divided from APP causes apoptotic neurotoxicity in AD brain. However, recent evidence suggests that CT105, carboxy terminal 105 aminoacids peptide fragment of APP, may be an important factor causing neurotoxicity in AD. SK-N-SH cells expressed with CT105 exhibited remarkable apoptotic cell damage. Based on morphological observations by phase contrast microscope and NO formation in the culture media, the CT105-induced cell death was significantly inhibited by POD. In addition, AD is one of brain degeneration disease. So We studied on herbal medicine that have a relation of brain degeneration. From old times, In Oriental Medicine, PO water extract has been used for disease in relation to brain degeneration. We were examined by ROS formation, neurite outgrowth assay and DPPH scravage assay. Additionally, we investigated the association between the CT105 and neurite degeneration caused by CT105-induced apoptotic response in neurone cells. We studied on the regeneratory and inhibitory effects of anti-Alzheimer disease in pCT105-induced neuroblastoma cell lines by POD. Findings from our experiments have shown that POD inhibits the synthesis or activities of CT105, which has neurotoxityies and apoptotic activities in cell line. In addition, treatment of POD(>50 ㎍/㎖ for 12 hours) partially prevented CT(105)-induced cytotoxicity in SK-N-SH cell lines, and were inhibited by the treatment with its. POD(>50 ㎍/㎖ for 12 hours) repaired CT105-induced neurite outgrowth when SK-N-SH cell lines was transfected with CT105. As the result of this study, In POD group, the apoptosis in the nervous system is inhibited, the repair against the degerneration of Neuroblastoma cells by CT105 expression is promoted. Decrease of memory induced by injection of scopolamin into rat was also attenuted by POD, based on passive avoidance test. Taken together, POD exhibited inhibition of CT105-induced apoptotic cell death. POD was found to reduce the activity of AchE and induced about the CA1 in rat hippocampus. Base on these findings, POD may be beneficial for the treatment of AD.

• Journal of Life Science
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• v.29 no.10
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• pp.1164-1170
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• 2019

The present study was carried out to evaluate extracts of Ginko biloba's outer seed coat, their antioxidative effects, and their ability to protect against DNA damage due to hydrogen peroxide ($H_2O_2$) treatments in cultured human keratinocyte (HaCaT) cells. The bioassays applied for determining the antioxidant effects of a G. biloba outer seed coat water extract (GOSWE) and a G. biloba outer seed coat methanol extract (GOSME) included the DPPH and $H_2O_2$ radical scavenging assays. Our results revealed that GOSME had higher activity than GOSWE against $H_2O_2$ radical scavenging activity in in vitro and in vivo bioassays. Treatment with GOSME significantly increased the viability of $H_2O_2-treated$ HaCaT cells. GOSME's ability to protect against DNA damage was observed via the analysis of plasmids in vitro and genomic DNA in $H_2O_2-treated$ HaCaT cells. According to our data, GOSME is able to protect HaCaT cells from $H_2O_2-induced$ DNA damage and apoptosis by blocking cellular damage related to oxidative stress. In conclusion, our study indicated GOSME might serve as a novel agent for the treatment and prevention of skin disorders caused by oxidative stress.

• International Journal of Oral Biology
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• v.32 no.2
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• pp.51-57
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• 2007

Cyclosporin A (CsA) plays an important role in clinical medicine and basic biology as an immunosuppressant and a mitochondrial permeability blocker, respectively. It was reported that CsA has a protective role by preventing apoptosis and promoting the proliferation in severed neurons. However, the molecular mechanisms for CsA-induced neuronal cell proliferation are unclear. In this study, we examined the mechanisms underlying the CsA-induced proliferation of PC12 cells. CsA increased the viability of PC12 cells in a dose(over $0.1{\sim}10\;{\mu}M$)-and time-dependent manner. The level of ROS generation was decreased in the CsA-treated PC12 cells. Expression of Bcl-2, an antiapoptotic molecule that inhibits the release of cytochrome c from the mitochondria into the cytosol, was upregulated, whereas Bax, a proapototic molecule, was not changed in the CsA-treated PC12 cells. CsA downregulated the mRNA expression of VDAC 1 and VDAC 3, but VDAC 2 was not changed in the CsA-treated PC12 cells. The level of cytosolic cytochrome c released from the mitochondria and the caspase-3 activity were attenuated in the CsA-treated PC12 cells. These results suggest that the mitochondria-mediated apoptotic signal and Bcl-2 family may play an important role in CsA-induced proliferation in PC12 cells.

• BMB Reports
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• v.37 no.4
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• pp.454-459
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• 2004

Experimental hyperoxia represents a suitable in vitro model to study some pathogenic mechanisms related to oxidative stress. Moreover, it allows the investigation of the molecular pathophysiology underlying oxygen therapy and toxicity. In this study, a modified experimental set up was adopted to accomplish a model of moderate hyperoxia (50% $O_2$, 96 h culture) to induce oxidative stress in the human leukemia cell line, U-937. Spectrophotometric measurements of mitochondrial respiratory enzyme activities, NMR spectroscopy of culture media, determination of antioxidant enzyme activities, and cell proliferation and differentiation assays were performed. The data showed that moderate hyperoxia in this myeloid cell line causes: i) intriguing alterations in the mitochondrial activities at the levels of succinate dehydrogenase and succinate-cytochrome c reductase; ii) induction of metabolic compensatory adaptations, with significant shift to glycolysis; iii) induction of different antioxidant enzyme activities; iv) significant cell growth inhibition and v) no significant apoptosis. This work will permit better characterization the mitochondrial damage induced by hyperoxia. In particular, the data showed a large increase in the succinate cytochrome c reductase activity, which could be a fundamental pathogenic mechanism at the basis of oxygen toxicity.

• Food Science and Preservation
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• v.22 no.5
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• pp.751-757
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• 2015

The objective of this study was to investigate the protective effects of mulberry (Morus alba) sugar extracts (MSE) against $H_2O_2$-induced oxidative stress in HepG2 cells. The MSEs was mixed with matured mulberry and sugar at the same ratio (1:1, w/w) and stored at $18{\pm}3^{\circ}C$ for 40 days. In 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging test, MSE stored for 40 days showed high activity with a ratio above 66%. Therefore, we selected 40 days as the optimum storage period. After cell viability analysis using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we determined that the optimum concentration of MSE was 0.5%. Our results showed that MSE increased the cell viability and antioxidant enzyme activities of superoxide dismutase (SOD) and catalase in $H_2O_2$-treated HepG2 cells. Moreover, the treatment with MSE inhibited malondialdehyde (MDA) levels in $H_2O_2$-treated HepG2 cells. We also observed a reduction in apoptotic bodies in the Hoechst staining. These data show that MSE treatment significantly suppressed caspase-3 activity in HepG2 cells expored to $H_2O_2$-induced oxidative stress, thereby indicationg the protective effects of MSE in $H_2O_2$-induced oxidative stress.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.6
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• pp.659-670
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• 2017

Oxidative stress and inflammation are key factors responsible for progression of liver injury. A variety of functions of oyster hydrolysate (OH) are affected by their antioxidant and anti-inflammatory activities. However, little is known regarding the effects of OH on a liver injury model. This study was performed to evaluate the effects of OH on acute liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN) in mice. Experimental groups were divided into six groups as follows (each group, n=10): control (saline), LPS/D-GalN, LPS/D-GalN+OH (100 mg/kg), LPS/D-GalN+OH (200 mg/kg), LPS/D-GalN+OH (400 mg/kg), and LPS/D-GalN+silymarin (25 mg/kg, positive control). The experimental acute liver injury model was induced with LPS ($1{\mu}g/kg$) and D-GalN (400 mg/kg). We first analyzed antioxidant and anti-inflammatory activities in OH. OH showed high DPPH and ABTS radical scavenging activities and reduced ROS generation in Chang cells in a dose-dependent manner. In addition, OH showed anti-inflammatory activities, such as inhibition of cyclooxygenase-2 and 5-lipooxygenase. Treatment with OH down-regulated tumor necrosis factor $(TNF)-{\alpha}$, interleukin (IL)-6, and $IL-1{\alpha}$ expression levels in LPS-stimulated RAW264.7 cells. OH significantly reduced LPS/D-GalN-induced increases in the concentrations of alanine transaminase and aspartate aminotransferase in serum. In the LPS/D-GalN group, liver tissues exhibited apoptosis of hepatocytes with hemorrhages. These pathological alterations were ameliorated by OH treatment. Consistently, hepatic catalase activity was low in the LPS/D-GalN group compared to the control group, and catalase activity was significantly restored by OH treatment (P<0.05). Furthermore, OH markedly reduced the LPS/D-GalN-induced increase in $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 levels in liver tissue. Taken together, these results show that OH has hepatoprotective effects on LPS/D-GalN-induced acute liver injury via inhibition of oxidative stress and inflammation, suggesting that OH could be used as a health functional food and potential therapeutic agent for acute liver injury.

• Korean Journal of Food Science and Technology
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• v.49 no.4
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• pp.430-437
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• 2017

The protective effect of Pteridium aquilinum on high glucose-induced cytotoxicity was examined in vitro to investigate the relationship between diabetic condition and neuronal dysfunction. The ethyl acetate fraction of P. aquilinum (EFPA), with total phenolic content of 265.08 mg gallic acid equivalent/g, showed higher 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)/2,2-diphenyl-1-picrylhydrazyl radical scavenging activities and lipid peroxidation inhibitory effect than any other fraction. In addition, EFPA showed a significant reduction in the inhibitory effect on ${\alpha}$-glucosidase activity ($IC_{50}$ value=$205.26{\mu}g/mL$) compared to the acarbose positive control. The anti-oxidative effect in PC12 cells, protective effects on high glucose-induced oxidative stress in neuronal cells, and neurotoxicity were measured using 2',7'-dichlorofluorescin diacetate, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide, and lactate dehydrogenase assays, respectively. EFPA showed conspicuous inhibitory effect on cellular reactive oxygen species production and neuronal cell apoptosis. Finally, kaempferol-3-glucoside was identified as the main phenolic compound of EFPA using high performance liquid chromatography.