• Nutrition Research and Practice
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• v.14 no.4
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• pp.334-351
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• 2020

BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson's trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS: These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

• Journal of Dental Anesthesia and Pain Medicine
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• v.17 no.1
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• pp.37-46
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• 2017

Background: In oxidative stress, reactive oxygen species (ROS) production contributes to cellular dysfunction and initiates the apoptotic cascade. Autophagy is considered the mechanism that decreases ROS concentration and oxidative damage. Propofol shows antioxidant properties, but the mechanisms underlying the effect of propofol preconditioning (PPC) on oxidative injury remain unclear. Therefore, we investigated whether PPC protects against cell damage from hydrogen peroxide ($H_2O_2$)-induced oxidative stress and influences cellular autophagy. Method: COS-7 cells were randomly divided into the following groups: control, cells were incubated in normoxia (5% $CO_2$, 21% $O_2$, and 74% $N_2$) for 24 h without propofol; $H_2O_2$, cells were exposed to $H_2O_2$ ($400{\mu}M$) for 2 h; $PPC+H_2O_2$, cells pretreated with propofol were exposed to $H_2O_2$; and 3-methyladenine $(3-MA)+PPC+H_2O_2$, cells pretreated with 3-MA (1 mM) for 1 h and propofol were exposed to $H_2O_2$. Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide thiazolyl blue (MTT) reduction. Apoptosis was determined using Hoechst 33342 staining and fluorescence microscopy. The relationship between PPC and autophagy was detected using western blot analysis. Results: Cell viability decreased more significantly in the $H_2O_2$ group than in the control group, but it was improved by PPC ($100{\mu}M$). Pretreatment with propofol effectively decreased $H_2O_2$-induced COS-7 cell apoptosis. However, pretreatment with 3-MA inhibited the protective effect of propofol during apoptosis. Western blot analysis showed that the level of autophagy-related proteins was higher in the $PPC+H_2O_2$ group than that in the $H_2O_2$ group. Conclusion: PPC has a protective effect on $H_2O_2$-induced COS-7 cell apoptosis, which is mediated by autophagy activation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.2
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• pp.161-168
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• 2017

In this study, we examined the effect of Perilla frutescens extract (PFE) on oxidative stress-induced cell death in RGC-5 cell lines. Staurosporine-differentiated RGC-5 (ssdRGC-5) cells obtained by treating RGC-5 cells with $1{\mu}M$ staurosporine were incubated with PFE for 30 min and then exposed to buthionine sulfoximine plus glutamate (B/G) for 20 h. Cell death was detected using lactate dehydrogenase release assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. To investigate the mechanism underlying cell death, we determined caspase-3 activity, level of reactive oxygen species (ROS) formation, and expression levels of cytoplasmic cytochrome c and mitochondrial Bax. Treatment of ssdRGC-5 cells with B/G increased intracellular ROS and induced apoptosis with increasing caspase-3 activity. PFE rescued ssdRGC-5 cells from oxidative stress-induced cell death by inhibiting intracellular ROS production and caspase-3 activation and regulating apoptosis-related proteins such as cytochrome c and Bax. These findings suggest that PFE may have a beneficial neuroprotective effect against oxidative stress-induced apoptotic death in ssdRGC-5 cells.

• BMB Reports
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• v.47 no.10
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• pp.569-574
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• 2014

Heme oxygenase-1 (HO-1) degrades heme to carbon dioxide, biliverdin, and $Fe^{2+}$, which play important roles in various biochemical processes. In this study, we examined the protective function of HO-1 against oxidative stress in SH-SY5Y cells and in a Parkinson's disease mouse model. Western blot and fluorescence microscopy analysis demonstrated that PEP-1-HO-1, fused with a PEP-1 peptide can cross the cellular membranes of human neuroblastoma SH-SY5Y cells. In addition, the transduced PEP-1-HO-1 inhibited generation of reactive oxygen species (ROS) and cell death caused by 1-methyl-4-phenylpyridinium ion ($MPP^+$). In contrast, HO-1, which has no ability to transduce into SH-SY5Y cells, failed to reduce $MPP^+$-induced cellular toxicity and ROS production. Furthermore, intraperitoneal injected PEP-1-HO-1 crossed the blood-brain barrier in mouse brains. In a PD mouse model, PEP-1-HO-1 significantly protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity and dopaminergic neuronal death. Therefore, PEP-1-HO-1 could be a useful agent in treating oxidative stress induced ailments including PD.

• BMB Reports
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• v.48 no.11
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• pp.618-623
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• 2015

FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI). In the cornea, there was a significant decrease in the number of cells expressing pro-inflammation, apoptotic, and angiogenic factors such as TNF-α, COX-2, and VEGF. Both corneal opacity and corneal neovascularization (CNV) were significantly decreased in the PEP-1-FK506BP treated group. Our results showed that PEP-1-FK506BP can significantly inhibit alkali burn-induced corneal inflammation in rats, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors and inflammatory cytokines. These results suggest that PEP-1-FK506BP may be a potential therapeutic agent for CAI.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6651-6661
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• 2015

Breast cancer is a global health concern and is a major cause of death among women. In Oman, it is the most common cancer in women, with an incidence rate of 15.6 per 100,000 Omani females. Various anticancer remedies have been discovered from natural products in the past and the search is continuing for additional examples. Cytotoxic natural compounds may have a major role in cancer therapy either in potentiating the effect of chemotherapy or reducing its harmful effects. Recently, a few studies have reported advantages of using crude camel milk in treating some forms of cancer. However, no adequate data are available on the lyophilised camel's milk responsibility for triggering apoptosis and oxidative stress associated with human breast cancer. The present study aimed to address the role of the lyophilised camel's milk in inducing proliferation repression of BT-474 and HEp-2 cells compared with the non-cancer HCC1937 BL cell line. Lyophilized camel's milk fundamentally repressed BT-474 cells growth and proliferation through the initiation of either the intrinsic and extrinsic apoptotic pathways as indicated by both caspase-3 mRNA and its action level, and induction of death receptors in BT-474 but not the HEp-2 cell line. In addition, lyophilised camel's milk enhanced the expression of oxidative stress markers, heme-oxygenase-1 and reactive oxygen species production in BT-474 cells. Increase in caspase-3 mRNA levels by the lyophilised camel's milk was completely prevented by the actinomycin D, a transcriptional inhibitor. This suggests that lyophilized camel's milk increased newly synthesized RNA. Interestingly,it significantly (p<0.003) repressed the growth of HEp-2 cells and BT-474 cells after treatment for 72 hours while 24 hours treatment repressed BT-474 cells alone. This finding suggests that the lyophilised camel's milk might instigate apoptosis through initiation of an alternative apoptotic pathway.

• The Journal of Internal Korean Medicine
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• v.41 no.1
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• pp.1-13
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• 2020

Objectives: Osteoarthritis (OA) is a chronic and degenerative joint disease characterized by progressive degeneration of articular cartilage. Inflammation is a recognized and important factor of OA progression. The present study was designed to investigate the protective effect of Corni Fructus water extract (CFW) on a monosodium iodoacetate (MIA)-induced rat model of OA. Methods: Osteoarthritis was induced by injection of MIA (50 µL; 80 mg/mL) into the knee joint cavity of rats. After an adaptation period for seven days, the rats were divided into 4 groups (n=8/group): normal, control, indomethacin-treated (5 mg/kg), and CFW-treated (200 mg/kg) groups. The rats were treated orally for 14 days. Pain was evaluated by determining hind paw weight distribution. For biochemical analyses, we measured the changes in reactive oxygen species (ROS) and peroxynitrite (ONOO^-) in the knee joint. The presence of anti-oxidant proteins and inflammatory proteins was determined by western blotting. Results: The administration of CFW significantly improved the hind paw weight distribution. The ROS and ONOO^- levels of knee joint were significantly decreased in the CFW group. CFW inhibited the production of inflammatory mediators, such as COX-2, and inflammatory cytokines, including IL-6 and IL-1β, via the NF-κB signaling pathway. The expression of anti-oxidant enzymes, such as catalase and GPx-1/2 also increased significantly. Conclusions: The findings indicate that CFW has a therapeutic and protective effect on OA by suppression of inflammation. Therefore, CFW could represent a potential and effective candidate for OA treatment.

• Toxicological Research
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• v.22 no.1
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• pp.23-30
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• 2006

Among poly aromatic hydrocarbons, dioxin and PCBs are the most controversial environmental pollutants in our modern life. These pollutants are known as human carcinogens, and liver is the most sensitive target in animal cancer models. Specific aims of the study were focused on the mechanism of carcinogenesis in hepatocytes and the structure-activity relation among these diverse environmental chemicals. Because key mechanisms of dioxin-induced carcinogenesis in human epithelial cell model are the alteration of signal transduction pathway and PKC isoforms, the alteration of the signal transduction pathways and other factors associated with carcinogenesis were studied. Rat hepatocytes cultured under the sandwich protocols were exposed with the various concentration of dioxins and PCBs, and signal transduction pathway, protein kinase C isoforms, oxidant stress, and apoptotic nuclei were evaluated. Since it is important to understand the structure-activity relation among these chemicals to properly assess the carcinogenic potentials, the study analyzed the parameters associated with carcinogenic processes, based on their structural characteristics. In addition, signal transduction pathways and PKC isoforms involved in inhibition of UV-induced apoptosis were also analyzed to elaborate the tumor promotion mechanism of these chemicals. Induction of apoptosis by UV irradiation was optimal at $60\;J/m^2$ in primary hepatocyte in culture. Compared to non coplanar PCBs such as PCB 114 and PCB 153, coplanar PCBs such as PCB 77 and PCB126 showed a stronger inhibition of apoptosis induced by UV irradiation. Production of reactive oxygen species (ROS) was more stimulated by non-coplanar PCBs than coplanar PCBs with the most potent induction of ROS by chlorinated non-coplanar PCB. As compared to the level of induction by PCB126, non-coplanar PCB153 showed a higher increase of intracellular concentrations. Besides the alteration of intracellular calcium concentration, translocation of PKC from cytosolic fraction to membrane fraction was clearly observed upon the exposure of non-coplanar PCB. Taken together, the present study demonstrated that there is a potent structure-activity relationship among PCB congeners and the mechanism of PAH-induced carcinogenesis is structure-specific. The study suggested that more diverse pathways of PAH-induced carcinogenesis should be taken into account beyond the boundary of Ah receptor dogma to assess the health impact of PAH with more accuracy.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.9
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• pp.1247-1255
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• 2016

Heparin binding proteins (HBPs) are produced by accessory glands. These are secreted into the seminal fluid, bind to the spermatozoa at the time of ejaculation, favour capacitation, acrosome reaction, and alter the immune system response toward the sperm. The present study was conducted with an objective to assess the effect of purified seminal plasma-HBPs (SP-HBPs) on cross bred cattle bull sperm attributes during two phases of cryopreservation: Pre freezing and freezing-thawing. SP-HBPs were purified from pooled seminal plasma by heparin affinity chromatography. Three doses of SP-HBPs i.e. 10, 20, $40{\mu}g/mLs$ semen were standardized to find out the optimum dose and $20{\mu}g/mLs$ was found to be an optimum dose. Semen as such and treated with SP-HBPs was diluted with sodium citrate-egg yolk diluter and cryopreserved as per the standard protocol. Sperm parameters i.e. motility, viability, Hypo-osmotic swelling test (HOST), acrosome damage, in vitro capacitation and lipid peroxidation were evaluated in SP-HBP treated and untreated (control) semen at both phases of cryopreservation. A considerable variation in percent sperm motility, viability, membrane integrity (HOST), acrosome damage, acrosome reaction and lipid peroxidation was observed at both phases among the bulls irrespective of the treatment. Incubation of neat semen with $20{\mu}g/mL$ SP-HBP before processing for cryopreservation enhanced the average motility, viability, membrane integrity by 7.2%, 1.5%, 7.9%, and 5.6%, 6.6%, 7.4% in pre-frozen and frozen-thawed semen in comparison to control. There was also an average increase of 4.1%/3.9% in in vitro capacitation and acrosome reaction in SP-HBPs-treated frozen-thawed semen as compared to control. However, binding of SP-HBPs to the sperm declined acrosome damage and lipid peroxidation by 1.3%/4.1% and 22.1/$32.7{\mu}M$/$10^9$ spermatozoa in SP-HBP treated pre-frozen/frozen-thawed semen as compared to control, respectively. Significant (p<0.05) effects were observed only in motility, HOST and in vitro acrosome reaction. It can be concluded that treatment of neat semen with SP-HBPs before cryopreservation minimized the cryoinjury by decreasing the generation of reactive oxygen species.

• Journal of Mushroom
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• v.16 no.3
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• pp.213-217
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• 2018

This study was carried out to identify medicinal mushrooms with protective effects against oxidative stress in PC12 neuronal cell line, followed by evaluation of their antioxidant property. Extracts of medicinal mushrooms, including Ganoderma lucidum extract (GLE), antler-shaped Ganoderma lingzhi extract (AGLE), Hericium erinaceus extract (HEE), and Sanghuangporus baumii extract (SBE), were screened for cytotoxicity using MTT assay. None of the extracts up to $10{\mu}g/ml$ concentration affected cell viability. These extracts were further checked for their protective effect against oxidative stress-induced reactive oxygen species (ROS) production. Exposure to $50{\mu}M$ $H_2O_2$ induced ROS generation in PC12 cells, which was inhibited only by treatment with AGLE. In addition, inhibition of $H_2O_2-induced$ ROS generation by AGLE was found to be in a dose-dependent manner (2.5, 5, and $10{\mu}g/ml$). Microscopic examination of DCF fluorescence for detection of ROS showed a similar pattern. Further, antioxidant activity of AGLE was determined by ABTS radical cation assay, and its $IC_{50}$ was found to be $46.90{\pm}0.31{\mu}g/ml$. Taken together, these results suggest that AGLE may help to alleviate oxidative stress in PC12 neuronal cells.