• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.167-181
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• 1991

The present study was an attempt to investigate the effect of forskolin on secretion of catecholamines (CA) evoked by Ach, excess $K^+$, DMPP, McN-A-343 and caffeine from the isolated perfused rat adrenal glands and to elucidate its mechanism of action. The perfusion with forskolin (1.0 uM) for 1 min into the adrenal vein enhanced markedly the secreation of CA evoked by Ach (50 ug), excess $K^+$ (56 mM) DMPP (100 uM) and by caffeine (0.3 mM) but did not that by McN-A-343. Forskolin alone did not potentiate the CA secretion. Moreover, forskolin augmented the CA release evoked by the above same stimulation even in the absence of extracellular calcium. The 1 min perfusion of 300 uM-dibutyryl cyclic AMP (DBcAMP), which is known to increase cyclic AMP levels, led to enhancement of Ca secretion evoked by Ach, excess $K^+$ and DMPP but did not that by McN-A-343 and caffeine. DBcAMP by itself also did not augment the CA secretion. In the calcium-free medium DBcAMP significantly enhanced the CA secretion by the same stimulation, except for the case of McN-A-343. These experimental results suggest that forskolin activates adenylate cyclase, resulting the elevation of cyclic AMP which may potentiate cholinergic nicotinic receptor-mediated and also depolarization-dependent CA secretion and that it may alter the intracellular calcium homeostasis in the rat adrenal glands.

• Animal cells and systems
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• v.2 no.4
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• pp.483-488
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• 1998

We previously found that a potent gonadotropin-releasing hormone (GnRH) agonist, buserelin, decreases GnRH promoter activity together with GnRH mRNA level, providing evidence for an autoregulatory mechanism operating at the level of GnRH gene transcription in immortalized GT1-1 neuronal cells. To examine whether agonist-induced decrease in GnRH mRNA level requires the continuous presence of buserelin, we performed a pulse-chase experiment of buserelin treatment. Short-term exposure (15 min) of GT1-1 neuronal cells to buserelin ($10{\mu}M$) was able to decrease GnRH mRNA levels when determined 24 h later. When GT1-1 cells were treated with buserelin ( $10{\mu}M$) for 30 min and then incubated for 1, 3, 6, 12, 24, and 48 h after buserelin removal, a significant decrease in GnRH mRNA levels was observed after the 12 h incubation period. These data indicate that inhibitory signaling upon buserelin treatment may occur rapidly, but requires a long time (at least 12 h) to significantly decrease the GnRH mRNA level. To examine the possible involvement of de novo synthesis and/or mRNA stability in buserelin-induced decrease in GnRH gene expression, actinomycin D ($5{\mu}m/ml$), a potent RNA synthesis blocker, was co-treated with buserelin. Actinomycin D alone failed to alter basal GnRH mRNA Revel, but blocked the buserelin-induced decrease in GnRH mRNA level at 12 h of post-treatment. These data suggest that buserelin may exert its inhibitory action by altering the stability of GnRH mRNA. Moreover, a polvsomal RNA separation by sucrose gradient centrifugation demonstrated that buserelin decreased the translational efficiency of the transcribed GnRH mRNA. Taken together, these results clearly indicate that GnRH agonist buserelin acts as an inhibitory signal at multiple levels such as transcription mRNA stability, and translation.

• Korean Journal of Plant Resources
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• v.27 no.1
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• pp.22-28
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• 2014

In this study, we conducted the anti-HIV-1 enzymes assay in vitro and its active components were predicted by QSAR in silico for the elucidation of action mechanism on anti-HIV of natural resources. The extracts of Gardenia jasminoides var. radicans Makino were tested for their inhibitory effects on the reverse transcriptase (RT), protease and ${\alpha}$-glucosidase. In the enzyme inhibition assay, the methanol extracts of Gardenia jasminoides var. radicans Makino stem showed a strong activity of 32.5% on the enzyme activity to cleave an oligopeptide, resembling one of the cleavage sites in the viral polyprotein which can only be processed by HIV-1 protease. Moreover the methanol extracts of stem exhibited alpha-glucosidase inhibitory activities of 26.1%. The methanol extracts ($100{\mu}g/ml$) of stem showed a weak activity of 13.4% on anti-HIV-1 RT using Enzyme Linked Oligonucleotide Sorbent Assay (ELOSA) method. However, all extracts of leaf and stem didn't exhibit the HIV-1-induced cytopathic effects with IC (inhibitory concentration) of $100{\mu}g/ml$ in HIV-1-infected human T-cell line. From these results, it is suggested that Gardenia jasminoides var. radicans Makino extracts may possibly be involved in the inhibition of reverse transcriptase, protease and alpha-glucosidase but can't vitally concerned with the viral replication in vitro.

• Korean Journal of Medicinal Crop Science
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• v.25 no.4
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• pp.231-237
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• 2017

Background: Cisplatin is one of the most extensively used chemotherapeutic agents for the treatment of cancer, including bladder, and ovarian cancers. However, it has been shown to induce nephrotoxicity, despite being an outstanding anti-cancer drug. In this study, we investigated the protective effect of dopaol ${\beta}$-D-glucoside (dopaol) on cisplatin-induced nephrotoxicity. Methods and Results: To confirm the protective effect of dopaol on cisplatin-induced nephrotoxicity, HK-2 cells were treated with $20{\mu}M$ cisplatin and $80{\mu}M$ dopaol. Cisplatin increased apoptosis, caspase-3 activity and mitochondrial dysfunction; however pretreatment with $80{\mu}M$ dopaol successfully attenuated apoptosis, caspase-3 activity and mitochondrial dysfunction. To evaluate the protective effect dopaol on cisplatin-induced nephrotoxicity in vivo, we used an animal model (balb/c mice, 20 mg/kg, i.p. once/day for 3 day). The results were similar to those obtained using HK-2 cells; renal tubular damage and neutrophilia induced by cisplatin reduced following dopaol injection (10 mg/kg, i.p. once/day for 3 day). Conclusions: These results indicate that dopaol treatment reduced cisplatin-induced nephrotoxicity in vitro and in vivo, and can be used to treat cisplatin-induced nephrotoxicity. However, further studies are required to determine the toxicity high dose dopaol and the signal pathways involved in its mechanism of action in animal models.

• Journal of Life Science
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• v.26 no.7
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• pp.847-854
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• 2016

Cordycepin, a derivative of the nucleoside adenosine, is one of the active components extracted from fungi of genus Cordyceps, and has been shown to have many pharmacological activities. In this study, we investigated the effects of cordycepin on proliferation and apoptosis of human gastric cancer AGS cells, and its possible mechanism of action. Treatment of cordycepin resulted in significant decrease in cell viability of AGS cells in a concentration-dependent manner. A concentration-dependent apoptotic cell death was also measured by agarose gel electrophoresis and flow cytometery analysis. Molecular mechanistic studies of apoptosis unraveled cordycepin treatment resulted in an enhanced expression of tumor necrosis factor-related apoptosis-inducing ligand, death receptor 5 and Fas ligand. Furthermore, up-regulation of pro-apoptotic Bax, and down-regulation of anti-apoptotic Bcl-2 and Bcl-xL expression were also observed in cordycepin-treated AGS cells. These were followed by activation of caspases (caspase-9, -8 and -3), subsequently leading to poly (ADP-ribose) polymerase cleavage. Taken together, these findings indicate that cordycepin induces apoptosis in AGS cells through regulation of multiple apoptotic pathways, including death receptor and mitochondria. Although further mechanical studies are needed, our results revealed that cordycepin can be regarded as a new effective and chemopreventive compound for human gastric cancer treatment.

• Journal of Life Science
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• v.31 no.1
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• pp.1-9
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• 2021

Brown seaweeds have been shown to decrease blood glucose levels and improve insulin sensitivity previously. In this study, we investigated the effect of fucoidan, a complex polysaccharide derived from brown seaweeds, on glucose uptake to improve insulin resistance, and examined its mechanism of action in 3T3-L1 adipocytes. We observed that fucoidan significantly increased glucose uptake and it was related to an increased expression of plasma membrane-glucose transporter 4 (PM-GLUT4) in 3T3-L1 adipocytes. Fucoidan treatment increased the activation of phosphatidylinositol-3-kinase (PI3K) and the phosphorylation of insulin receptor substrate 1 (IRS1tyr) compared with that of the control cells. Fucoidan also promoted the phosphorylation of Akt and protein kinase C (PKC)-λ/ζ compared to that of the control cells. Moreover, fucoidan significantly upregulated acetyl-CoA-carboxylase (ACC) and adenosine monophosphate - activated protein kinase (AMPK) phosphorylation. As a result, translocation of GLUT4 was significantly enhanced in 3T3-L1 adipocytes, which significantly promoted glucose uptake via the PI3K/AMPK pathways. The elevation of glucose uptake by fucoidan was blocked by inhibitor of PI3K and inhibitor of AMPK in 3T3-L1 adipocytes. These findings indicate that fucoidan might ameliorate glucose uptake through GLUT4 translocation to the plasma membrane by activating the PI3K/Akt and AMPK pathways in 3T3-L1 adipocytes. Fucoidan is thought to be of high material value to diabetes treatments and functional foods.

• Journal of Applied Biological Chemistry
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• v.65 no.4
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• pp.239-245
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• 2022

Although normal activation of platelets is important in the process of hemostasis, excessive or abnormal activation of platelets can lead to cardiovascular diseases. Therefore, the discovery of novel substances capable of regulating or inhibiting platelet activation may be helpful in the prevention and treatment of cardiovascular diseases. Artemether is a derivative of artemisinin, known as an active ingredient of Artemisia annua, which has been reported to be effective in treating malaria, and is known to function through antioxidant and metabolic enzyme inhibition. However, the role of artemether in platelet activation and aggregation and the mechanism of action of artemether in collagen-induced human platelets are not known until now. This study investigated the effects of artemether on platelet activation and thrombus formation induced by collagen. As a result, cAMP level was significantly increased by artemether, and VASP and IP3R, substrates of cAMP-dependent kinase, were phosphorylated. IP3R phosphorylation by Artemether inhibited Ca²⁺ recruitment into the cytoplasm, and phosphorylated VASP inhibited fibrinogen binding by inactivating αIIb/β3 located on the platelet membrane. Consequently, artemether inhibited thrombin-induced fibrin clot formation. Therefore, we propose that artemether can act as an effective prophylactic and therapeutic agent for cardiovascular diseases caused by excessive platelet activation and thrombus formation.

• Journal of Life Science
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• v.34 no.4
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• pp.227-235
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• 2024

Hepatocyte damage caused by medications or herbal products is one of the important problem when these compounds are chronically administrated. Thus, improving hepatocyte survival during treatment offers a wide range of opportunities. Valproic acid (VPA), a branched short-chain fatty acid derived from naturally occurring valeric acid, is commonly used to treat epilepsy and seizures. Although VPA exerts numerous effects in cancer, HIV therapy, and neurodegenerative disease, its effects on the liver and its mechanism of action have not been fully elucidated. Here, we demonstrated that VPA caused moderate liver cell toxicity and apoptosis. Interestingly, VPA treatment increased transcription levels of PPAR alpha (PPAR-α) and fibroblast growth factor 21 (FGF21) in murine (Hepa1c1c7) hepatoma cells in a time and concentration dependent manner. VPA-induced FGF21 expression was significantly weaker under PPAR-α silencing condition than in cells transfected with non-targeting control siRNA. Subsequent experiments showed that cell viability was significantly lowered when the FGF21 signaling pathway was blocked by FGF receptor antagonist. Finally, we further determined that AMPK phosphorylation was not responsible for VPA-induced FGF21 expression and PPAR-a increments. These results indicate that increases of FGF21 expression alleviate VPA-induced hepatic toxicity, thereby making FGF21 a potential biomarker for predicting liver damage during VPA treatments.

• Journal of Dental Rehabilitation and Applied Science
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• v.29 no.1
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• pp.1-9
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• 2013

This study examined the effects of the occlusal stability and a partial coverage mouthguard on physical fitness and motor capacity to determine the importance of the occlusal stability as a possible action mechanism of mouthguards on physical performance. Twenty physical education students were included for measurements of their handgrip strength, back strength, whole body reaction time, flexibility, sidestep test, stork stand test and jumping test according to the following 5 different occlusal conditions: mouth closed position without a mouthguard, with a full coverage mouthguard, with a right partial coverage mouthguard, with a left partial coverage mouthguard and with anterior partial mouthguard. The results revealed no significant difference in any of the measured physical factors between the occlusal conditions with and without a full-coverage mouthguard. On the other hand, a significant difference was observed in whole body reaction between the occlusal conditions with and without the partial coverage mouthguards. Therefore, isokinetic muscle tests on both knee joints and the Wingate anaerobic power test should be performed under the following five occlusal conditions: with or without full-coverage maxillary custom-made mouthguard, with a unilateral right or left partial-coverage maxillary mouthguard and with an anterior partial-coverage maxillary mouthguard. These results suggest that the partial coverage mouthguard had a short-term beneficial effect on agility rather than full coverage mouthguard.

• Journal of Life Science
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• v.25 no.9
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• pp.1000-1006
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• 2015

α-Asarone is the main component of Acorus gramineus, which is a widely used oriental traditional medicine. A. gramineus is known to have a variety of medicinal effects, such as anti-gastric ulcer, antiallergy and antioxidant activity. It is also known to inhibit the release of histamine. However, the mechanism of its action remains unclear in humans. In this study, the effects of α-asarone on matrix metalloproteinase (MMP) and its antioxidant effect in a cell-free system were examined in HT1080 cells. In an MTT assay, the effect of α-asarone on cell viability showed no cytotoxicity below 16 μM. In an antioxidant assay, α-asarone increased reducing power in a dose-dependent manner but not the scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. In addition, α-asarone exhibited the protective effect against DNA oxidation induced by hydroxyl radicals produced by the Fenton reaction. Furthermore, in a gelatin disk assay, α-asarone enhanced collagenase activity. It also increased the activities of MMP-2 and MMP-9 stimulated by phorbol 12-myristate 13-acetate (PMA) in a gelatin zymography. On the other hand, the activity of MMP-9 stimulated by phenazine methosulfate (PMS) but not that of MMP-2 was increased in the presence of α-asarone. These findings suggest that α-asarone could be a candidate for the prevention and treatment of pathological diseases related to oxidative stress and MMPs.