• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.92-100
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• 2019

Ginger, one of worldwide consumed dietary spice, is not only famous as food supplements, but also believed to exert a variety of remarkable pharmacological activity as herbal remedies. In this study, a ginger constituent, 12-dehydrogingerdione (DHGD) was proven that has comparable anti-inflammatory activity with positive control 6-shogaol in inhibiting LPS-induced interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, prostaglandin (PG) $E_2$, nitric oxide (NO), inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, without interfering with COX-1 in cultured microglial cells. Subsequent mechanistic studies indicate that 12-DHGD may inhibit neuro-inflammation through suppressing the LPS-activated $Akt/IKK/NF-{\kappa}B$ pathway. Furthermore, 12-DHGD markedly promoted the activation of NF-E2-related factor (Nrf)-2 and heme oxygenase (HO)-1, and we demonstrated that the involvement of HO-1 on the production of pro-inflammatory mediators such as NO and $TNF-{\alpha}$ by using a HO-1 inhibitor, Zinc protoporphyrin (Znpp). These results indicate that 12-DHGD may protect against neuro-inflammation by inhibiting $Akt/IKK/I{\kappa}B/NF-{\kappa}B$ pathway and promoting Nrf-2/HO-1 pathway.

• BMB Reports
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• v.52 no.5
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• pp.342-347
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• 2019

Methylation is a primary epigenetic mechanism regulating gene expression. 5-aza-2'-deoxycytidine is an FDA-approved drug prescribed for treatment of cancer by inhibiting DNA-Methyl-Transferase 1 (DNMT1). Results of this study suggest that prolonged treatment with 5-aza-2'-deoxycytidine could induce centrosome abnormalities in cancer cells and that CEP131, a centrosome protein, is regulated by DNMT1. Interestingly, cancer cell growth was attenuated in vitro and in vivo by inhibiting the expression of Cep131. Finally, Cep131-deficient cells were more sensitive to treatment with DNMT1 inhibitors. These findings suggest that Cep131 is a potential novel anti-cancer target. Agents that can inhibit this protein may be useful alone or in combination with DNMT1 inhibitors to treat cancer.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.420-428
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• 2023

Background: Ginsenoside F2 (GF2), a minor component of Panax ginseng, has been reported to possess a wide variety of pharmacological activities. However, its effects on glucose metabolism have not yet been reported. Here, we investigated the underlying signaling pathways involved in its effects on hepatic glucose. Methods: HepG2 cells were used to establish insulin-resistant (IR) model and treated with GF2. Cell viability and glucose uptake-related genes were also examined by real-time PCR and immunoblots. Results: Cell viability assays showed that GF2 up to 50 μM did not affect normal and IR-HepG2 cell viability. GF2 reduced oxidative stress by inhibiting phosphorylation of the mitogen-activated protein kinases (MAPK) signaling components such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK, and reducing the nuclear translocation of NF-κB. Furthermore, GF2 activated PI3K/AKT signaling, upregulated the levels of glucose transporter 2 (GLUT-2) and GLUT-4 in IR-HepG2 cells, and promoted glucose absorption. At the same time, GF2 reduced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression as well as inhibiting gluconeogenesis. Conclusion: Overall, GF2 improved glucose metabolism disorders by reducing cellular oxidative stress in IR-HepG2 cells via MAPK signaling, participating in the PI3K/AKT/GSK-3β signaling pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.345-356
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• 2023

This study aimed to assess the effects of exogenous hydrogen sulfide (H₂S) on abdominal aorta coarctation (AAC) induced myocardial fibrosis (MF) and autophagy in rats. Forty-four Sprague-Dawley rats were randomly divided into control group, AAC group, AAC + H₂S group, and H₂S control group. After a model of rats with AAC was built surgically, AAC + H₂S group and H₂S group were injected intraperitoneally with H₂S (100 µmol/kg) daily. The rats in the control group and the AAC group were injected with the same amount of PBS. We observed that H₂S can improve left ventricular function and the deposition of myocardial collagen fibers, inhibit pyroptosis, down-regulate the expression of P-eif2α in myocardial tissue, and inhibit cell autophagy by activating the phosphatidylinositol 3-kinase (PI3K)/AKT1 signaling pathway (p < 0.05). In addition, angiotensin II (1 µM) H9c2 cardiomyocytes were injured in vitro experiments, and it was also observed that pyroptosis was inhibited after H₂S (400 µmol/kg) intervention, the expression of P-eif2α in cardiomyocytes was significantly down-regulated, and the PI3K/AKT1 signaling pathway was activated at the same time. Therefore, increasing the expression of P-eif2α reverses the activation of the PI3K/AKT1 signaling pathway by H₂S. In conclusion, these findings suggest that exogenous H₂S can ameliorate MF in rats with AAC by inhibiting pyroptosis, and the mechanism may be associated with inhibiting the phosphorylation of eif2α and activating the PI3K/AKT1 signaling pathway to inhibit excessive cell autophagy.

• Animal cells and systems
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• v.3 no.2
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• pp.103-113
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• 1999

Many in-depth reviews related to regulations of prolactin secretion are available. We will, therefore, focus on controversial aspects using personal opinion in this review. The neuroendocrine control of prolactin secretion from the anterior pituitary gland involves multiple factors including prolactin-release inhibiting factor (PIF) and prolactin releasing factor (PRF). The PIF exerts a tonic inhibitory control in the physiological conditions. The PIF should be able to effectively inhibit prolactin release or a lifetime, but the inhibitory action of dopamine cannot be sustained for a long period of time. Perifusion of a high concentration of dopamine (l ,000 nM) could not sustain inhibitory action on prolactin release but when a small amount of ascorbic acid (0.1 mM) is added in a low concentration of dopamine (3 nM) solution, prolactin release was inhibited for a long period. Ascorbate is essential for dopamine action to inhibit prolactin release. We have, therefore, concluded that the PIF is dopamine plus ascorbate. The major transduction system for dopamine to inhibit prolactin release is the adenylyl cyclase system. Dopamine decreases cyclic AMP concentration by inhibiting adenylyl cyclase, and cyclic AMP stimulates prolactin release. However, the inhibitory mechanism of dopamine on prolactin release is much more complex than simple inhibition of CAMP production. The dopamine not only inhibits cyclic AMP synthesis but also inhibits prolactin release by acting on a link(s) after the CAMP event in a chain reaction for inhibiting prolactin release. Low concentrations of dopamine stimulate prolactin release. Lactotropes are made of several different subtypes of cells and several different dopamine receptors are found in pituitary. The inhibitory and stimulatory actions induced by dopamine can be generated by different subtype of receptors. The GH$_4$ZR$_7$ cells express only the short isoform (D$_{2s}$) of the dopamine receptor, as a result of transfecting the D$_{2s}$ receptors into GH$_4$C$_1$ cells which do not express any dopamine receptors. When dopamine stimulates or inhibits prolactin release in GH$_4$ZR$_7$ cells, it is clear that the dopamine should act on dopamine D$_{2s}$ receptors since there is no other dopamine receptor in the GH$_4$ZR$_7$. Dopamine is able to stimulate prolactin release in a relatively low concentration while it inhibits in a high concentration in GH$_4$ZR$_7$. These observations indicate that the dopamine D$_2$ receptor can activate stimulatory and/or inhibitory transduction system depending upon dopamine concentrations.

• Journal of the korean academy of Pediatric Dentistry
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• v.26 no.3
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• pp.459-465
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• 1999

The inhibition degree of the isolated bacteria on plaque formation of Streptococcus mutans, and the effect of these bacterial genus on the concentration of total bacteria in saliva were assessed with the following. The effectiveness of the isolated bacteria on the inhibition of plaque formation was assessed culturing Streptococcus mutans in the beaker with orthodontic wires. The mean weight of plaque produced on a wire was 152mg in the culture of Streptococcus mutans only, whereas being reduced to 4mg, 78mg, or 72mg in the combined culture of Streptococcus mutans and Enterococcus durans, Lactobacillus acidophilus, or Streptococcus oralis. The colony forming units (CFU) of Streptococcus mutans were $3.6{\times}10^8$ per ml in the culture of Streptococcus mutans, only, wheras being $1.4{\times}10^6,\;5.6{\times}10^6,\;or\;3.8{\times}10^6$ per ml in the combined culture of Streptococcus mutans and Enterococcus durans, Lactobacillus acidophilus, or Streptococcus oralis. When saliva from children was inoculated on brain heart infusion agar, the colony forming units of bacteria were $4.8{\times}10^6\;to\;1.3{\times}10^9$ per ml of saliva. The concentration of Enterococcus, Lactobacillus, or Streptococcus inhibiting Streptococcus mutans in saliva was not proportioned to that of total bacteria replicated on brain heart infusion agar. These results indicate that the isolated bacteria inhibited the replication of Streptococcus mutans, resulting into inhibiting the formation of plaque, but the concentration of Enterococcus, Lactobacillus, or Streptococcus inhibiting Streptococcus mutans, in saliva might not affect the total bacterial concentration of saliva.

• Korean Journal of Weed Science
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• v.17 no.3
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• pp.325-333
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• 1997

Selection of pepper (Capsicum sp.) cultivars tolerant to acetolactate synthase (ALS)-inhibiting herbicides {imazethapyr, 2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-5-ethyl-3=pyridine-carboxylic acid, and primisulfuron methyl 2-[[[[[4,6-bis(difluoromethoxy)-2-pyrimidinyl]amino] carbonyl]amino]sulfonyl]benzoate} was investigated. Pepper cultivars such as Red Top, Happy Dry, Golden Tower, and Hagyeorae showed relatively tolerant response to imazethapyr, while cultivars; Korea, Cheongyang, Oriental Glory, and Hanam were susceptible. Red Horn, Jopoong, Kwangbok, and Wangcho cultivars were tolerant to primisulfuron whereas Korea, Dahhong, Chamjoah, and Poongchon cultivars were susceptible. Determination of growth inhibition by ALS-inhibiting herbicides showed that the $I_{50}$ estimates of growth from the susceptible- and tolerant-cultivars were 0.075 and 0.20kg ai/ha for imazethapyr; 0.06 and 0.16kg ai/ha for primisulfuron, respectively. Furthermore, the $GR_{50}$ estimates of growth from the susceptible and tolerant cultivars were 0.05 and 0.20kg ai/ha for imazethapyr; 0.07 and 0.16kg ai/ha for primisulfuron, respectively. This result, based on the $GR_{50}$ and $I_{50}$ values, indicates that responses of pepper to ALS-inhibiting herbicides between tolerant- and susceptible-cultivars were different about 3- to 4-fold to imazethapyr, and 2- to 3-fold to primisulfuron.

• Herbal Formula Science
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• v.25 no.3
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• pp.391-412
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• 2017

Objective : In this study, we searched the experimental research about combined treatment of anticancer drug and herbal medicine for killing or inhibiting proliferation of Cancer cells searched in OASIS and KISS. This study aimed to analyze the experimental research paper about anticancer drug combined treatment with herbal medicine. Methods : We collected the research paper including killing or inhibiting proliferation of Cancer cells in OASIS and KISS using keyword anticancer drug with herbal medicine, tumor suppressor with herbal medicine, inhibition of Cancer with herbal medicine and combined treatment with herbal medicine. Assorting by cancer cells, we analyzed experimental results cancer cell viability, anticancer drug dosage, tumor weight and survival rate. Also, we checked the effects of herbal medicine on cancer and additive effect reducing side effect of anticancer drug. Results : Total 45 studies were selected. 38 studies reported combined treatment of anticancer drug and herbal medicine was more effective than only anticancer drug. The death of cancer cells was synergistically induced by the cotreatment of anticancer drug and herb extracts. The studies suggest that the cotreatment of anticancer drug and herb extracts could reduce side effect of anticancer drug. In addition, some studies reported cotreatment mechanism like apoptotic death signal processes. In combined treatment of anticancer drug and herb extracts, The expression of Fas/Fas L, Bax, Bcl2, Caspase-3 etc.. was markedly increased in cancer cells. Conclusions : Our results suggest that anticancer drug combined treatment with herbal medicine could be efficient for killing or inhibiting proliferation of cancer cells. However, this paper had some limitation as follows: First, collected studies have been published only for korean journal. Second, results of research and effects of combined treatment are not collected objectively. To solve these problems, more objective and balanced studies should be performed.

• Research in Plant Disease
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• v.8 no.4
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• pp.239-244
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• 2002

Among 34 isolates of Colletotrichum spp., 20 from red pepper and 14 from apple, only one isolate 2001-45 was identified as the isolate resistant to sterol biosynthesis inhibiting fungicides. EC$_{50}$ values of the isolate 2001-45 were 153.5, 42.7, 34.0, and 17.1 $\mu\textrm{g}$/ml for myclobutanil, tebuconazole, hexaconazole and nuarimol, respectively, The resistance factor of the isolate 2001-45 against the other isolate 2001-44 to 4 above fungicides was ranged from 17 to 57. However, EC$_{50}$ value of the 2001-45 for prochloraz was 0.07 $\mu\textrm{g}$/ml, which was lower than those of the 2001-44 and the isolate JC24. For the fitness test of the 2001-45, mycelial growth, sporulation on PDA and pathogenicity on fruits were investigated. No difference in mycelial growth was found between 2001-45 and 2001-44, but great difference in sporulation. No symptom was developed by 2001-45 even by wound inoculation of pepper fruit. Therefore, this study indicated that the isolate 2001-45 was inferior to the other isolates in the fitness, although the isolate 2001-45 was highly resistant to sterol biosynthesis inhibiting fungicides.

• Journal of Nutrition and Health
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• v.34 no.5
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• pp.513-524
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• 2001

This study was performed to investigate the effects of dry powders, ethanol extracts and juices of radish and onion on lipid metabolism, lipid peroxidation and antioxidative enzyme activity in rats. Forty-nine male Sprague-Dawley rats weighing 157$\pm$6g were blocked into seven groups according to body weight and raised for four weeks with diets containing 5%(w/w) dry powders of two different vegetables consumed frequently by Korean-radish(Raphanus sativus L.) and onion(Allium cepa L.), ethanol extracts and juices from equal amount of each dry powder. All the powders, ethanol extracts and juices of radish and onion decreased total lipids, triglycerides and total cholesterol concentrations in plasma and liver. Above all, onion ethanol extract decreased them most remarkably. It was thought that organosulfur compounds and flavonoids extracted from onion by ethanol inhibited biosynthesis and absorption of lipid and promoted degradation of lipid. Radish powder also decreased them by increasing fecal excretions of total lipids, triglycerides and total cholesterol most effectively. Catalase and glutathine peroxidase(GSH-px) activities in red blood cell(RBC) were most remarkably increased by radish powder and onion powder respectively. Superoxide dismutase(SOD), catalase and GSH-px activities in liver were most remarkably increased by onion ethanol extract, radish powder and onion ethanol extract respectively. Xanthine oxidase(XOD) activities in liver were most effectively decreased by ethanol extracts of radish and onion. Thiobarbituric acid reactive substance (TBARS) levels in plasma and liver of experimental groups were significantly lower than those of controls. Above all, onion powder decreased them most effectively. It was thought that vitamin E and high flavonoids in onion powder inhibited lipid peroxidation, promoting liver and RBC SOD, catalase and GSH-px activities and inhibiting XOD activities effectively. Flavonoids in onion ethanol extract inhibited lipid peroxidation, promoting three antioxident enzyme activities and inhibiting XOD activities most remarkably. Also flavonoids and high vitamin C in radish powder inhibited lipid peroxidation, promoting liver and RBC catalase most remarkably and inhibiting XOD activities. In conclusion, radish and onion were effective in lowering lipid levels and inhibiting of lipid peroxidation in animal tissue. From these data, radish and onion can be recommended in the treatment and prevention of diseases such as cardiovascular disease and cancer and in delaying aging. As ethanol from onion were most effective in lowering lipid level and promoting three antioxident enzymes, and inhibited lipid peroxidation as did we should try to utilize onion skin which is discarded though reported to have abundant flavonoids. (Korean J Nutrition 34(5) : 513~524, 2001)