• YAKHAK HOEJI
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• v.47 no.2
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• pp.104-109
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• 2003

The present paper reviews the notion and comparison of the Korea Food and Drug Administration(KFDA) general pharmacology and the International Conference on Harmonisation (ICH) safety pharmacology. General pharmacology or safety pharmacology is termed the study to determine the potential of a compound to induce adverse pharmacological effects. KFDA general pharmacology studies have been considered an important component in drug safety assessment and these were originally referred to those designed to examine effects other than the primary therapeutics effect of a drug candidate. The KFDA notified the Guideline for General Pharmacology in 1997. Safety pharmacology studies were focused on identifying adverse effects on physiological functions. In the ICH came into place S7A Safety Pharmacology Studies for Human Pharmaceuticals in 2001. A new chemical entity should be assessed for its side effects, initially in those physiological systems which are generally agreed to be the key systems that are essential for life; these "core system" include the central nervous system, cardiovascular system and respiratory system in safety pharmacology studies. These studies should be performed in compliance with Good Laboratory Practice (GLP).

• Journal of Ginseng Research
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• v.48 no.3
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• pp.298-309
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• 2024

Background: 20(S)-ginsenoside Rh2(GRh2), an effective natural histone deacetylase inhibitor, can inhibit acute myeloid leukemia (AML) cell proliferation. Lactate regulated histone lactylation, which has different temporal dynamics from acetylation. However, whether the high level of lactylation modification that we first detected in acute promyelocytic leukemia (APL) is associated with all-trans retinoic acid (ATRA) resistance has not been reported. Furthermore, Whether GRh2 can regulate lactylation modification in ATRA-resistant APL remains unknown. Methods: Lactylation and METTL3 expression levels in ATRA-sensitive and ATRA-resistant APL cells were detected by Western blot analysis, qRT-PCR and CO-IP. Flow cytometry (FCM) and APL xenograft mouse models were used to determine the effect of METTL3 and GRh2 on ATRA-resistance. Results: Histone lactylation and METTL3 expression levels were considerably upregulated in ATRA-resistant APL cells. METTL3 was regulated by histone lactylation and direct lactylation modification. Overexpression of METTL3 promoted ATRA-resistance. GRh2 ameliorated ATRA-resistance by downregulated lactylation level and directly inhibiting METTL3. Conclusions: This study suggests that lactylation-modified METTL3 could provide a promising strategy for ameliorating ATRA-resistance in APL, and GRh2 could act as a potential lactylation-modified METTL3 inhibitor to ameliorate ATRA-resistance in APL.

• Toxicological Research
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• v.22 no.2
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• pp.109-116
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• 2006

Safety pharmacology studies are conducted to investigated the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above. In the International Conference on Harmonisation (ICH), the guideline 'S7A: Safety Pharmacology Studies for Human Pharmaceuticals' has been developed and reached Step 5 of the ICH process in 2001. Now the Korea Food and Drug Administration (KFDA) are going to transfer 'The Guideline for General Pharmacology' into 'The Guideline for Safety Pharmacology'. Safety pharmacology studies should be performed in compliance with Good Laboratory Practice (GLP). Thus, the present paper reviews the Japanese GLP guidelines for pharmaceuticals to help the conduct and inspection of safety pharmacology studies in compliance with GLP. We also reviewed the ICH guidelines 'S7B revised : The Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals' and 'E14 : The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-antiarrhythmic Drugs' to apply our drug approval systems.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.160-165
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• 1993

The effects of Glycyrrhizae Radix (GR) on the metabolism of acetaminophen (AA) were examined in male Sprague-Dawley rats. The methanol extract of GR (500 mg/kg) was administered orally to rats for 6 days. AA and its metabolites excreted in bile, urine and blood within 120 min after dosing of AA (150 mg/kg, i.v.) were assayed by HPLC. Treatment of rats with the methanol extract of GR significantly increased the cumulative biliary excretion of AA-glucuronide (156% of the control) and decreased that of AA-sulfate (63% of the control). The cumulative urinary excretion of AA-glucuronide was also significantly increased to 132% of the control. GR treatment significantly increased total (biliary plus urinary) excretion of AA-glucuronide (172% of the control) without influencing thioether and sulfate conjugates of AA. The results clearly show that GR enhances UDP-glucuronosyl transferase-mediated detoxication of AA, but may not influence sulfotrans-ferase-mediated and cytochrome P-450-mediated metabolites formation.

• Journal of Ginseng Research
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• v.47 no.1
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• pp.9-22
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• 2023

As a famous herbal medicine in China and Asia, ginseng (Panax ginseng C. A. Meyer) is also known as the "King of All Herbs" and has long been used in medicine and healthcare. In addition to the obvious biological activities of ginsenosides, ginseng polysaccharides (GPs) exhibit excellent antitumor, antioxidant stress, and immunomodulatory effects. In particular, GPs can exert an antitumor effect and is a potential immunomodulator. However, due to the complexity and diversity in the structures and components of GPs, their specific physicochemical properties, and underlying mechanisms remain unclear. In this article, we have summarized the factors influencing the antitumor activity of GPs and their mechanism of action, including the stimulation of the immune system, regulation of the gut microbiota, and direct action on tumor cells

• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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• pp.38-46
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• 2007

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.178-178
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• 1996

Hepatitis B virus (HBV) infection is one of the serious problems in Southeast Asia including Korea because it causes chronic hepatitis, which can easily be transformed In fatal conditions such as cirrhosis and hepatoma. Even though lots of informations on structural characteristics and gene expression mechanisms have been accumulated, the mechanism for HBV-induced hepatocellular injury which is believed to be the consequences of the immunological response is not well understood. In order tn perform immunopathological studies for prevention and treatment of HBV infection, we designed transgenic mice as a disease model which can mimic HBV infection, In this study, a promoter-HBV DNA fragment for the preparation of HBV transgenic mice has been constructed. To add a proper enzyme site on 5' end of HBV gene, total HBV (subtype adr) gene was inserted into BamHI site of pBluescript SK vector and reextracted by PstI-SacI treatment A liver-specific promoter, rat ${\alpha}$ 2u globulin gene promoter, was insrted to pBluescript SK vector and reextracted by BamHI-PstI treatment, Promoter-HBV DNA was constructed by ligation of two fragments using identical PstI sites. For large scale production of promoter-HBV DNA, it was inserted to BamHI-SacI site of pBluescript SK vector.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.93-93
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• 1995

The three combined products were prepared as suspended solutions composed of various ratio of Sucralfate, Hydrotalcite and Neusilin, into which 30% ethanol extracts of Machili cortex, and of Atractylodis rhizoma were added. The efficacy for these products was examined in vivo using a pyrous ligation method in rats. The influence of these products on the intestinal motility was also examined in mice. In all experimental setting, the antisecretory effect of the combined treatment was more pronounced than that of each drug alone. The combined treatment consisted of Sucralfate, Hydrotalcite, Neusilin ratios of 2:2:1 produced the highest inhibitory effect for the gastric secretion. The intestinal motility was not influenced significantly by the treatment of all experimental setting. The above results revealed that the therapeutic dose of Sucralfate, Hydrotalcite, Neusilin given in combination showed a synergistic effect for the inhibition of gastric secretion and little side effect on the intestinal motility. Therefore, the combined product with Sucralfate, Hydrotalcite, Neusilin ratio of 2:2:1 is recommended for the useful drug to heal the gastrointestinal diseases with no side effect on the intestinal motility.

• Journal of Ginseng Research
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• v.44 no.4
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• pp.580-592
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• 2020

Background: Radix et Rhizoma Ginseng (thereafter called ginseng) has been used as a medicinal herb for thousands of years to maintain people's physical vitality and is also a non-organ-specific cancer preventive and therapeutic traditional medicine in several epidemiologic and preclinical studies. Owing to few toxic side effects and strong enhancement on body immunity, ginseng has admirable application potential and value in cancer chemoprevention. The study aims at investigating the chemopreventive effects of ginseng on cutaneous carcinoma and the underlying mechanisms. Methods: The mouse skin cancer model was induced by 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate. Ultraperformance liquid chromatography/mass spectrometry was used for identifying various ginsenosides, the main active ingredients of ginseng. Comprehensive approaches (including network pharmacology, bioinformatics, and experimental verification) were used to explore the potential targets of ginseng. Results: Ginseng treatment inhibited cutaneous carcinoma in terms of initiation and promotion. The content of Rb1, Rb2, Rc, and Rd ginsenosides was the highest in both mouse blood and skin tissues. Ginseng and its active components well maintained the redox homeostasis and modulated the immune response in the model. Specifically, ginseng treatment inhibited the initiation of skin cancer by enhancing T-cell-mediated immune response through upregulating HSP27 expression and inhibited the promotion of skin cancer by maintaining cellular redox homeostasis through promoting nuclear translocation of Nrf2. Conclusion: According to the study results, ginseng can be potentially used for cutaneous carcinoma as a chemopreventive agent by enhancing cell-mediated immunity and maintaining redox homeostasis with multiple components, targets, and links.

• Safety and Health at Work
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• v.5 no.2
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• pp.106-111
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• 2014

Background: The manufacture of paint involves a variety of processes that present with medical hazards. Safety initiatives are hence introduced to limit hazard exposures and promote workplace safety. This aim of this study is to assess the use of available control measures/initiatives in selected paint factories in Lagos West Senatorial District, Nigeria. Methods: A total of 400 randomly selected paint factory workers were involved in the study. A well-structured World Health Organization standard questionnaire was designed and distributed to the workers to elicit information on awareness to occupational hazards, use of personal protective devices, and commonly experienced adverse symptoms. Urine samples were obtained from 50 workers randomly selected from these 400 participants, and the concentrations of the heavy metals (lead, cadmium, arsenic, and chromium) were determined using atomic absorption spectroscopy. Results: The results show that 72.5% of the respondents are aware of the hazards associated with their jobs; 30% have had formal training on hazards and safety measures; 40% do not use personal protective devices, and 90% of the respondents reported symptoms relating to hazard exposure. There was a statistically significant (p < 0.05) increase in the mean heavy metal concentrations in the urine samples obtained from paint factory workers as compared with nonfactory workers. Conclusion: The need to develop effective frameworks that will initiate the integration and ensure implementation of safety regulations in paint factories is evident. Where these exist, there is a need to promote adherence to these practice guidelines.