• Journal of Ginseng Research
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• v.47 no.3
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• pp.376-384
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• 2023

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

• Journal of Life Science
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• v.27 no.9
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• pp.1070-1077
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• 2017

Chondrocyte apoptosis induced by reactive oxygen species (ROS) plays an important role in the pathogenesis of osteoarthritis. Schisandrin A, a bioactive compound found in fruits of the Schisandra genus, has been reported to possess multiple pharmacological and therapeutic properties. Although several studies have described the antioxidant effects of analogues of schisandrin A, the underlying molecular mechanisms of this bioactive compound remain largely unresolved. The present study investigated the cytoprotective effect of schisandrin A against oxidative stress (hydrogen peroxide [$H_2O_2$]) in SW1353 human chondrocyte cells. The results showed that schisandrin A preconditioning significantly inhibited $H_2O_2-induced$ growth inhibition and apoptotic cell death by blocking the degradation of poly (ADP-ribose) polymerase proteins and down-regulating pro-caspase-3. These antiapoptotic effects of schisandrin A were associated with attenuation of mitochondrial dysfunction and normalization of expression changes of proapoptotic Bax and antiapoptotic Bcl-2 in $H_2O_2-stimulated$ SW1353 chondrocytes. Furthermore, schisandrin A effectively abrogated $H_2O_2-induced$ intracellular ROS accumulation and phosphorylation of histone H2AX at serine 139, a widely used marker of DNA damage. Thus, the present study demonstrates that schisandrin A provides protection against $H_2O_2-induced$ apoptosis and DNA damage in SW1353 chondrocytes, possibly by prevention of ROS generation. Collectively, our data indicate that schisandrin A has therapeutic potential in the treatment of oxidative disorders caused by overproduction of ROS.

• Journal of Life Science
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• v.32 no.4
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• pp.310-317
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• 2022

Recently, interest in the harmful factors of particulate matter (PM), a major component of air pollution, has been increasing. In particular, PM_2.5 with a diameter of less than 2.5 ㎛ is well known to induce oxidative stress accompanied by autophagy in human lung epithelial cells. However, studies on whether PM_2.5 increases autophagy under oxidative stress and whether this process is reactive oxygen species (ROS)-dependent are insufficient. Therefore, in this study, we investigated whether PM_2.5 promotes autophagy through the generation of ROS in human alveolar epithelial A594 cells. According to our results, cells co-treated with PM_2.5 and hydrogen peroxide (H₂O₂) showed a lower cell viability than cells treated with each alone, which was associated with increased total and mitochondrial ROS production. The co-treatment of PM_2.5 and H₂O₂ also increased autophagy induction, which was confirmed through Cyto-ID staining, and the expression of autophagy biomarker proteins increased. However, when ROS generation was artificially blocked by N-acetyl-L-cysteine pretreatment, the reduction in cell viability and induction of autophagy by PM_2.5 and H₂O₂ co-treatment were markedly attenuated. Therefore, the present results suggest that PM_2.5-induced ROS generation may play a critical role in autophagy induction in A549 cells.

• Journal of Animal Science and Technology
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• v.55 no.4
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• pp.237-247
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• 2013

This study was to examine single or combined in vitro effects of environmental endocrine disruptors on boar sperm characteristics, oxidative stress damage in sperm and development of porcine IVF embryos. Addition of various concentration of NP (10, 20, $30{\mu}M$), DBP (10, 50, $100{\mu}M$) and BPA (1, 5 or $10{\mu}g/ml$) on boar sperm characteristics such as percentages of sperm motility, viability, membrane integrity and mitochondrial activity were dose-dependently decreased within 3, 6 or 9 hr incubation period (p<0.05). The overall detrimental effects increased with incubation time increasement. NP, DBP and BPA showed the detrimental effects on sperm membrane and mitochondria of energy production organelles affecting cell viability with the dependancy of dose and incubation time. In combination effects, NP ($10{\mu}M$) + DBP ($10{\mu}M$) significantly decreased boar general sperm characteristics for 3 or 6 hr incubation period compared with control (p<0.05). When both of NP and DBP concentrations (NP; $30{\mu}M$, DBP; $100{\mu}M$) increase, the detrimental effects on sperm characteristics were larger than those of low concentration combination (p<0.05). The inhibitory effects of NP ($30{\mu}M$) + BPA ($10{\mu}g/ml$) on sperm characteristics were larger than those of NP ($10{\mu}M$) + BPA ($1{\mu}g/ml$) (p<0.05). DBP ($100{\mu}M$) + BPA ($10{\mu}g/ml$) decreased sperm characteristics compared with the low concentration combination (DBP $10{\mu}M$ + BPA $1{\mu}g/ml$, p<0.05). This result indicates the detrimental effects of both chemicals on sperm characteristics were dose dependent. Addition of NP ($30{\mu}M$) + DBP ($100{\mu}M$), NP ($30{\mu}M$) + BPA ($10{\mu}g/ml$), DBP ($10{\mu}M$) + BPA ($1{\mu}g/ml$) or DBP ($100{\mu}M$) + BPA ($10{\mu}g/ml$) significantly increased lipid peroxidation for 3 or 6 hr incubation period (p<0.05) compared with no addition control. NP (${\geq}20{\mu}M$) decreased the percentages of IVF embryo development from morulae and blastocyst stages (p<0.05) and its detrimental effects were dose-dependant. BPA 0, 1, 5 or $10{\mu}g/ml$ decreased significantly and dose-dependently the percentage of morulae plus and blastocysts (p<0.05). Combinations of DBP ($100{\mu}M$) plus NP ($30{\mu}M$) and DBP ($100{\mu}M$) plus BPA ($10{\mu}g/ml$) did not affect on morulae and blastocyst development, but NP ($30{\mu}M$) plus BPA ($10{\mu}g/ml$) has significant detrimental effect on embryo development at these stages (p<0.05). These overall results indicate that the partial detrimental effects on boar sperm characteristics and embryo development by NP, DBP, BPA or the combination of these chemicals might be due to the increasement of lipid peroxidation and free radical formation in the cell and there were no specific interaction effects on boar sperm and embryo degeneration among the combined treatments.

• Biomedical Science Letters
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• v.2 no.1
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• pp.71-90
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• 1996

There is considerable current interest in the effect of regular vigorous exercise and in particular endurance-running as a possible measure in improving myocardial function. Some data indicate that the aging heart may actually suffer from vigorous endurance exercise. On the contrary appropriate exercise in aged animals improves myocardial function and aerobic energy metabolism. So far there is relatively little data to indicate that endurance exercise is in fact beneficial in improving myocardial function or damaging to heart of aged animals. The present investigation aimed to study the possible effect of a long range treadmill training program on the heart in aging rats. Male rats aged 3, 10, and 20 months were divided at random into a control (sedentary) and an exercise group. The training group was exercised for 5 days a week on an automated treadmill for 20minutes at 18m/min over a period of 5 months. The exercise regimen of our experiments did not cause any significant changes in the tissues and ultrastructural as com-pared with sedentary age-matched control. Tissues and ultrastructures of myocardial cells in trained group aged 8 months are intact and well organized as well as sedentary control group. Age associated tissue and ultrastructural changes of trained group aged 15 months included : an increase in transformed mitochondria, vacuoles, lysosomes, lipid droplets and early lipofuscin. But the trained heart did not show significant difference in tissue and ultrastructural properties from those of sedentary controls. Endurance-trained group aged 25 months showed significant qualitative tissue and ultrastructural difference as compared with age-matched controls. In addition to those found in 25 months control group, focal necrosis, myofibril fraying, hypercontraction band, seperation of intercalated discs, degenerating nucleus and infiltration of collagenous fiber into myocyte were noted in trained 25 months group. The stereological examination of the mi-crographs disclosed no significant difference in the myoflbril, mitochondrion, sarcotubule and in-terstitium volume density and surface density of mitochondrial cristae and numerical density of mitochondria between trained and control group aged 8 and 15 months. In the trained 25 months group, significant increase in volume density of interstitium, lipofucsin granule were shown as compared to untrained age-matched control. On the other hand, significant decrease in mitochondrion volume density was shown. The myofibril volume density did not differ between trained and control group although trained group showed slight increase. From the data obtained a reduced mitochondria/myofibrils ratio was found in trained rat heart aged 25 months and there was no difference between trained and control rat aged 15 months. But a slight but not significant increase was found in the trained group aged 8 months as compared with same age control group. Such increase in the ratio in young animals is considered to be of great importance to cardiac pumping and adaptability. Whereas such adaptations don't seem to occur in aged heart muscle. This study proposed that repeated endurance exercise do not cause any significant qualitative and quantitative ultrastructural change of heart muscle in young(3months) and adult (10months) suggesting that the heart is able to adapt to the exercise. On the contrary, the repeated endurance exercise stress may actually induce degenerative changes in the aged heart muscle(20months).

• Applied Microscopy
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• v.35 no.3
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• pp.165-176
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• 2005

Studies on molecular plasticity of Bermann glia (BG) after harmaline-induced Purkinje cell (PC) degeneration in the rat cerebellum. The intimate structural relationship between BG and PC, evidenced by the sheathing of the PC dendrites by veil-like process from the BG has been suggestive of the close functional relationship between these two cell types. However, little is known about metabolic couplings between these cells. This study designed to investigate molecular plasticity of BG in the rat cerebellum in which PCs were chemically ablated by harmaline treatment. Immunohistochemical examination reveals that harmaline induced PC degeneration causes a marked glial reaction in the cerebellum with activated BG and microglia aligned in parasagittal stripes within the vermis. In these strips, activated BG were associated with upregulaion of metallotheionein, while GLAST and was down regulated, as compared with nearby intact area where both BG are in contact with PCs. The data from this study demonstrate that BG can change their phenotypic expression when BG loose their contact with PCs. It is conceivable that activated BG may upregulate structural proteins, metallothionein expression to use for their proliferation and hypertrophy; metallothionein expression to cope with oxidative stress induced by PC degeneration and microglial activation. On the contrary, BG may down regulated expression of GLAST because sustained loss of contact with PCs would eliminate the necessity for the cellular machinery involved glutamate metabolism. In conclusion, BG might respond man to death of PCs by undergoing a change in metabolic state. It seems possible that signaling molecules released from PCs regulates the phenotype expression of BG. Also ultrastructures in the organelles of normal PC and BG are distinguished by mitochondrial appearance, and distributed vesicles at the synaptic area in the cytoplasm.

• Journal of Life Science
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• v.21 no.3
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• pp.435-443
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• 2011

The purpose of this study is to identify the effects of exercise training [ET, 10~18 m/min (speed), 20~30 min (exercise duration)/a day for 5 day/wk, 6 wk) on PGC-$1{\alpha}$, GLUT-1, Tfam, Cu,Zn-SOD and Mn-SOD proteins in brain of STZ-induced diabetic rats. The male Sprague-Dawley (SD) rats were single-injected intraperitoneally with 50mg/kg of streptozotocin (STZ) to produce STZ-induced diabetic rats. Rats were divided into 3 experimental groups with 8 rats in each group, as follows: (1) non-STZ group (n=8), (2) STZ-CON group (n=8), (3) STZ-EXE group (n=8). The results of this study suggest that i) serum glucose level was significantly reduced in STZ-EXE group compared with STZ-CON group (p<0.05), ii) PGC-$1{\alpha}$ (p<0.001), mtPGC-$1{\alpha}$ (p<0.001), GLUT-1 (p<0.001), and mtTfam (p<0.001) proteins in brain of STZ-induced diabetic rats were significantly increased in STZ-EXE group compared with STZ-CON group, iii) Cu,Zn-SOD (p<0.001) and Mn-SOD (p<0.01) proteins in the STZ-induced diabetic rats were significantly increased in STZ-EXE group compared with STZ-CON group. In conclusion, the findings of the present study reveal that treadmill exercise training increases brain GLUT-1 protein level possibly through up-regulation of PGC-$1{\alpha}$ and Tfam proteins which represent key regulatory components of stimulation of brain mitochondrial biogenesis. In addition, treadmill exercise training may prevent oxidative stress by up-regulation of Cu,Zn-SOD and Mn-SOD proteins in the STZ-induced diabetic rats.

• Journal of Nutrition and Health
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• v.54 no.6
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• pp.618-630
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• 2021

Purpose: The ginger rhizome (Zingiber officinale) is widely cultivated as a spice for its aromatic and pungent components. One of its constituents, 6-hydroxydopamine (6-OHDA) is usually thought to cross the cell membrane through dopamine uptake transporters, and induce inhibition of mitochondrial respiration and the generation of intracellular reactive oxygen species (ROS). This study examines the neuroprotective effect and acetylcholinesterase (AChE) inhibitory activity of fermented ginger extracts (FGEs) on 6-OHDA induced toxicity in SH-SY5Y human neuroblastoma cells. Methods: Ginger was fermented using 2 species of Bacillus subtilis, with or without enzyme pretreatment. Each sample was extracted with 70% ethanol. Neurotoxicity was assessed by applying the EZ-Cytox cell viability assay and by measuring lactic dehydrogenase (LDH) release. Morphological changes of apoptotic cell nuclei were observed by Hoechst staining. Cell growth and apoptosis of SH-SY5Y cells were determined by Western blotting and enzyme activity analysis of caspase-3, and AChE enzymatic activity was determined by the colorimetric assay. Results: In terms of cell viability and LDH release, exposure to FGE showed neuroprotective activities against 6-OHDA stimulated stress in SH-SY5Y cells. Furthermore, FGE reduced the 6-OHDA-induced apoptosis, as determined by Hoechst staining. The occurrence of apoptosis in 6-OHDA treated cells was confirmed by determining the caspase-3 activity. Exposure to 6-OHDA resulted in increased caspase-3 activity of SH-SY5Y cells, as compared to the unexposed group. However, pre-treatment with FGE inhibited the activity of caspase-3. The neuroprotective effects of FGE were also found to be caspase-dependent, based on reduction of caspase-3 activity. Exposure to FGE also inhibited the activity of AChE induced by 6-OHDA, in a dose-dependent manner. Conclusion: Taken together, our results show that FGE exhibits a neuroprotective effect in 6-OHDA treated SH-SY5Y cells, thereby making it a potential novel agent for the prevention or treatment of neurodegenerative disease.