• Toxicological Research
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• v.31 no.1
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• pp.1-9
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• 2015

Environmental toxicants such as toxic metals can alter epigenetic regulatory features such as DNA methylation, histone modification, and non-coding RNA expression. Heavy metals influence gene expression by epigenetic mechanisms and by directly binding to various metal response elements in the target gene promoters. Given the role of epigenetic alterations in regulating genes, there is potential for the integration of toxic metal-induced epigenetic alterations as informative factors in the risk assessment process. Here, we focus on recent advances in understanding epigenetic changes, gene expression, and biological effects induced by toxic metals.

• YAKHAK HOEJI
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• v.18 no.4
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• pp.236-242
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• 1974

Extrusion-spheronization processing combination was used to produce spherical granules with experimental formulations which contain microcrystalline cellulose as a diluent. The produced granules were compared on the basis of the following physical properties ; (a) bulk density, (e) porosity, (f) friabillity and (g) dissolution rate. With the specific experimental formulations used in this study, the increased plate rotational speeds of Marumerizer (400-1200rpm) produced continually more spherical material and also the obtained data indicated that the particle size distribution and dissolution rate depend upon the amount of microcrystalline cellulose used. As a result, the spherical granule preparation with microcrystalline cellulose has good properties in flow rate, packing propertyu and friability and offers a suitable method of granule preparation in pharmaceutical industry.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.249.2-250
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• 2002

Tolerance and pharmacolinetics after single-dose administration of DA-8159, a new selective PDE5 inhibitor under phase 1 study, were examined in 42 healthy male volunteers in a six-period, double-blinded placebo-controlled study. Participants received single oral tablet of DA-8159 (12.5 to 300mg) or placebo. Adverse effects and pharmacokinetic parameters were monitored during experiments. DA-8159 was well tolerated and the frequency of adverse events was dose-related. (omitted)

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.176-183
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• 2014

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta ($A{\beta}$) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Ab-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in $A{\beta}$-induced neurotoxicity. In mice with $A{\beta}$-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Ab-induced neurotoxicity. Moreover, HCW, which had an $IC_{50}$ value of $79.7{\mu}g/ml$ for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.

• Natural Product Sciences
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• v.14 no.4
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• pp.260-264
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• 2008

To find the antidiabetic activity of the tripterpenoid-rich fractions of Rubus coreanus (TRF-cor) and R. crataegifolius (TRF-cra) leaves or its main component niga-ichigoside $F_1$ (Niga-$F_1$), anti-hyperglycemic and antihyperlipidemic effects were investigated in the diabetic rat model induced by streptozotocin (STZ). Treatments of rats with 200 mg/kg of the TRF-cor, TRF-cra (each, p.o.) or 20 mg/kg of Niga-$F_1$ significantly inhibited the increase of blood glucose concentration about 44.8%, 28.7% or 20.6%, respectively, in the diabetic rats. In addition, treatments with those fractions inhibited the increase of serum concentrations of triglyceride, total cholesterol or LDL-cholesterol caused by STZ. The inhibitory rate on atherogenic index (AI) values of the TRFcor (200 mg/kg), TRF-cra (200 mg/kg) or Niga-$F_1$ (20 mg/kg)-treated groups were decreased about 55.7%, 36.3% or 22.6%, respectively, comparable to STZ-treated group. In the oral glucose tolerance test, treatment of TRF-cor or TRF-cra inhibited the increase of blood glucose concentration in the STZ-induced rats. Administration of 20 mg/kg of Niga-$F_1$ (p.o.) also exhibited similar effects with the effects of both TRFs at 200 mg/kg dose (p.o.). These results support that the triterpenoids, in particular Niga-$F_1$, are contributed to the antidiabetic effects of R. coreanus or R. crataegifolius.

• Journal of Ginseng Research
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• v.46 no.1
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• pp.39-53
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• 2022

Ginsenoside Rb₁ (Rb₁), one of the most important ingredients in Panax ginseng Meyer, has been confirmed to have favorable activities, including reducing antioxidative stress, inhibiting inflammation, regulating cell autophagy and apoptosis, affecting sugar and lipid metabolism, and regulating various cytokines. This study reviewed the recent progress on the pharmacological effects and mechanisms of Rb₁ against cardiovascular and nervous system diseases, diabetes, and their complications, especially those related to neurodegenerative diseases, myocardial ischemia, hypoxia injury, and traumatic brain injury. This review retrieved articles from PubMed and Web of Science that were published from 2015 to 2020. The molecular targets or pathways of the effects of Rb₁ on these diseases are referring to HMGB1, GLUT4, 11β-HSD1, ERK, Akt, Notch, NF-κB, MAPK, PPAR-γ, TGF-β1/Smad pathway, PI3K/mTOR pathway, Nrf2/HO-1 pathway, Nrf2/ARE pathway, and MAPK/NF-κB pathway. The potential effects of Rb₁ and its possible mechanisms against diseases were further predicted via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and disease ontology semantic and enrichment (DOSE) analyses with the reported targets. This study provides insights into the therapeutic effects of Rb₁ and its mechanisms against diseases, which is expected to help in promoting the drug development of Rb₁ and its clinical applications.

• The Korean Journal of Pain
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• v.37 no.1
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• pp.26-33
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• 2024

Background: Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of sitagliptin in formalin and carrageenan tests and determine the possible mechanism(s) of its antinociceptive activity. Methods: Male Swiss mice (25-30 g) and male Wistar rats (180-220 g) were used for formalin and carrageenan tests, respectively. In the formalin test, paw licking time and in the carrageenan test, paw thickness were considered as indexes of pain behavior and inflammation respectively. Three doses of sitagliptin (2.5, 5, and 10 mg/kg) were used in these tests. Also, several antagonists and enzyme inhibitors were used to evaluate the role of adrenergic, serotonergic, dopaminergic, and opioid receptors as well as the NO/cGMP/K_ATP pathway in the antinociceptive effect of sitagliptin (5 mg/kg). Results: Sitagliptin showed significant antinociceptive and anti-inflammatory effects in the formalin and carrageenan tests respectively. In the carrageenan test, all three doses of sitagliptin significantly (P < 0.001) reduced paw thickness. Pretreatment with yohimbine, prazosin, propranolol, naloxone, and cyproheptadine could not reverse the antinociceptive effect of sitagliptin (5 mg/Kg), which indicates that adrenergic, opioid, and serotonin receptors (5HT₂) are not involved in the antinociceptive effects. L-NAME, methylene blue, glibenclamide, ondansetron, and sulpiride were able to reverse this effect. Conclusions: NO/cGMP/K_ATP, 5HT₃ and D₂ pathways play an important role in the antinociceptive effect of sitagliptin. Additionally significant anti-inflammatory effects observed in the carrageenan test might contribute in reduction of pain response in the second phase of the formalin test.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3293-3297
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• 2014

Background: Pine needle oil from crude extract of pine needles has anti-tumor effects, but the effective component is not known. Methods: In the present study, compounds from a steam distillation extract of pine needles were isolated and characterized. Alpha-pinene was identified as an active anti-proliferative compound on hepatoma carcinoma BEL-7402 cells using the MTT assay. Results: Further experiments showed that ${\alpha}$-pinene inhibited BEL-7402 cells by arresting cell growth in the G2/M phase of the cell cycle, downregulating Cdc25C mRNA and protein expression, and reducing cycle dependence on kinase 1(CDK1) activity. Conclusion: Taken together, these findings indicate that ${\alpha}$-pinene may be useful as a potential anti-tumor drug.

• Biomolecules & Therapeutics
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• v.15 no.3
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• pp.169-174
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• 2007

In the present study, we investigated the neuroprotective effects of standardized Ginkgo biloba extract (GBB) (total terpene trilactones, 13 ${\pm}$ 3%; biflavone, 4.5 ${\pm}$ 1.5%; flavonol glycoside, < 8%; proanthocyanidine, under detection limit) on ischemia-reperfusion-induced brain injury in the rats. Ischemia was induced by the intraluminal occlusion of the right middle cerebral artery for 2 h and reperfusion was continued for 22 h. GBB was orally administered, promptly prior to reperfusion and 2 h after. Total infarction volume in the ipsilateral hemispheres of ischemia-reperfusion rats were significantly reduced by treatment with GBB in a dose-dependent manner (P<0.05). The therapeutic time window of GBB was 3 h in this ischemia-reperfusion rat model. Furthermore, GBB also significantly inhibited increased neutrophil infiltration of ischemic brain tissue, as estimated by myeloperoxidase activity. These findings suggest that GBB plays a crucial protective role in ischemia-induced brain injury, in part, via inhibition of neutrophil infiltration, and suggest that this GBB could serve as a neuroprotective agent following transient focal ischemic brain injury.

• Korean Journal of Pharmacognosy
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• v.48 no.2
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• pp.108-112
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• 2017

To isolate and identify the constituents of the fruit galls of Actinidium polygama as well as evaluate the anti-inflammatory effects of the isolated compounds, a total of five triterpenes were isolated including $2{\alpha},3{\alpha},24$-trihydroxy-12-ursene-23-al-28-oic acid (1), corosolic acid (2), $2{\alpha},3{\alpha},24$-trihydroxyurs-12,20(30)-dien-28-oic acid (3), $2{\alpha},3{\alpha},24$-trihydroxyolean-12-en-28-oic acid (4), and $2{\alpha},3{\alpha},24$-trihydroxyurs-12-en-28-oic acid (pygenic acid B) (5). Compounds 1, 3, and 4 were isolated from the fruit galls of A. polygama for the first time. Compound 3 decreased NO production in LPS-stimulated RAW264.7 macrophages and mouse microglia BV2 cells in a concentration-dependent manner.