• Title/Summary/Keyword: Safety pharmacology

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Effects of AIF on Knee Osteoarthritis Patients: Double-blind, Randomized Placebo-controlled Study

  • Park, Sung-Hoon;Kim, Seong-Kyu;Shin, Im-Hee;Kim, Hyung-Gun;Choe, Jung-Yoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.1
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    • pp.33-37
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    • 2009
  • Anti-inflammatory factor(AIF) is a water soluble extract of three herbs, Panax notoginseng(Burk.) F. H. Chen, Rehmannia glutinosa Libosch and Eleutherococcus senticosus. The present study aimed to investigate the safety and efficacy of herb extracts, AIF, on Korean knee osteoarthritis patients for six weeks. Fifty seven patients with knee osteoarthritis, ranging from 43 to 73 years of age, who fulfilled the "American College of Rheumatology"(ACR) classification of idiopathic osteoarthritis of knee and radiographic criteria were randomly selected and enrolled for the study. After initial screening and resting period, two capsules each of AIF(Each capsule contains; 400 mg) and similar identical placebo were administered twice a day to both groups. Pain intensity at second, fourth, and sixth weeks of study as well as one week after discontinuation of drugs was assessed by using 100 mm visual analogue scale(VAS). Changes in the Korean version of the Western Ontario and McMaster Universities(K-WOMAC) index score were compared at the initiation and completion of the study. VAS assessed by patients were significantly reduced(at visit 2; $54.64{\pm}14.72$, at visit 4, $37.32{\pm}16.58$, p<0.001) after AIF administration. Results showed an improvement in the physical function of K-WOMAC scale which was significantly higher(p=0.013) in AIF than placebo group, and decreases of total K-WOMAC score were also significantly higher(p=0.030) in AIF groups than placebo group. No serious adverse effect was observed, and there was no difference in incidence of adverse effect between AIF and placebo groups. In this population of Korean patients with knee osteoarthritis, AIF was found to be safe, tolerable and effective for symptomatic improvement of pain and physical function.

Anticancer Activity of Atractylodes lancea (Thunb.) DC in a Hamster Model and Application of PET-CT for Early Detection and Monitoring Progression of Cholangiocarcinoma

  • Plengsuriyakarn, Tullayakorn;Matsuda, Naoki;Karbwang, Juntra;Viyanant, Vithoon;Hirayama, Kenji;Na-Bangchang, Kesara
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6279-6284
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    • 2015
  • Opisthorchis viverrini (OV)-induced cholangiocarcinoma (CCA) is an important cancer in the Great Mekong region, particularly in Thailand. Limitations of treatment options and the lack of an effective diagnostic tool for early detection of CCA are major concerns for the control of this type of cancer. The aim of the study was to investigate anti-CCA activity of the ethanolic extract of Atractylodes lancea (Thunb.) DC., and the applicability of positron emission tomography-computed tomography (PET-CT) as a tool for detection and monitoring the progression of CCA in Opisthorchis viverrini (OV)/dimethylnitrosamine (DMN)-induced CCA hamsters. Male Syrian hamsters were used for toxicity tests and anti-CCA activity evaluation. Development of CCA was induced by initial feeding of 50 metacercariae of OV, followed by drinking water containing 12.5 ppm of DMN in hamsters. The ethanolic extract of A. lancea (Thunb.) DC. was administered orally for 30 days. PET-CT was performed every 4 weeks after initiation of CCA using 18F-fluorodeoxyglucose ($^{18}F-FDG$). Results from the present study suggest that the ethanolic extract of A. lancea (Thunb.) DC. rhizome exhibited promising anti-CCA activity and safety profile in the OV/DMN-induced hamster model. To successfully apply PET-CT as a tool for early detection of tumor development and progression, modification of radiolabeling approach is required to improve its specificity for CCA cells.

The Comparative Study of Anti-allergic Effect by Glycyrrhiza New Varieties and Official Compendia (감초 신품종 및 약전 수재감초의 항알러지 효과 비교 연구)

  • Kang, Yun-Mi;Kim, Wonnam;Jin, Jong-Sik;Lee, Jong-Hyun;Chang, Jae Ki;Lee, Jeonghoon;An, Hyo-Jin
    • The Korea Journal of Herbology
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    • v.35 no.5
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    • pp.13-21
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    • 2020
  • Objective : The genus Glycyrrhiza has been used in food and traditional herbal medicine. Many experimental studies reported that Glycyrrhiza species possess several pharmacological properties. Glycyrrhiza new varieties WONGAM and SINWONGAM have been developed by Korea Rural Development Administration doing research for registration on Ministry of Food and Drug Safety. During the evaluations about pharmacological effect of Glycyrrhiza new varieties WONGAM and SINWONGAM, we focused the anti-allergic effect in this study. Methods : We investigated the anti-allergic effect of WONGAM and SINWONGAM compared with Glycyrrhiza uralensis Fischer and G. glabra L. using anti-dinitrophenyl-immunoglobulin E (IgE)/human serum albumin-stimulated RBL-2H3 cells, phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 cells and compound 48/80-induced anaphylaxis mice model. We analyzed the effect on the expression of various cytokines, and IgE from mast cells and the underlying molecular mechanisms of WONGAM and SINWONGAM in presented models. Results : WONGAM and SINWONGAM showed the inhibitory effect on the histamine release from rat peritoneal mast cells or human mast cells without cytotoxicity. WONGAM and SINWONGAM blocked anaphylactic shock and decreased the IgE production. Furthermore, WONGAM and SINWONGAM inhibited the productions of TNF-α and IL-6 in compound 48/80-induced anaphylaxis mice model. Conclusion : These results indicated that WONGAM and SINWONGAM would have protect effect on allergic responses through the inhibition of allergic mediators and pro-inflammatory cytokines. This study may facilitate the development on Glycyrrhiza new varieties for allergy.

A literature study on dermatological efficacy and drug induced liver injury of Dictamnus dasycarpus Turcz (백선피(白鮮皮)의 피부과적 효능과 약인성 간손상에 대한 문헌 연구)

  • Lee, Youjung;Kim, Seoyoung;Kim, Hyungwoo
    • The Korea Journal of Herbology
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    • v.33 no.1
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    • pp.9-15
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    • 2018
  • Objectives : The root bark of Dictamnus dasycarpus has been frequently used to treat patients with skin diseases in Korea. Recently, wild root of D. dasycarpus are reported to induce liver injury. Methods : Traditional uses of D. dasycarpus for skin diseases were analysed bibliographically. In addition, reported cases were collected and analysed using pubmed and national digital library. Results : In taiwan, D. dasycarpus revealed to be one of major herbs for skin diseases and many researchers in worldwide had reported its dermatological efficacies. Reported cases related in liver injury described that hepatocellular or cholestatic liver injury were seen in patients eating wild root of D. dasycarpus. In addition, 6 cases in worldwide and 1 case in Korea showed that patients with drug induced liver injury (DILI) ingested not root bark of D. dasycarpus but prescriptions containing root bark of D. dasycarpus. These mean that wild root of D. dasycarpus (Bongsam or Bongwhangsam) was estimated to be closely related in DILI. Whereas, it was difficult to confirm direct correlation between root bark of D. dasycarpus used as herbal medicine by doctor of Korean medicine and DILI. Conclusions : these results imply that wild root of D. dasycarpus is closely related in DILI and strong recommendation not to take it without consultation by experts is needed. In addition, although there are no evidences of direct correlation between root bark of D. dasycarpus and DILI, doctor of Korean medicines should pay attention to use root bark of D. dasycarpus in their clinics.

Effects of Fragaria Orientalis Water Extract on Adipogenesis in Diet-induced Obese C57BL/6 Mice (Fragaria Orientalis 물 추출물이 고지방식이를 급여한 C57BL/6 Mice에서 비만 관련 인자에 미치는 영향)

  • Moon-Yeol Choi;Mi Hyung Kim;Mi Ryeo Kim
    • The Korea Journal of Herbology
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    • v.39 no.4
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    • pp.1-9
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    • 2024
  • Objective : In this study, the anti-obesity effect of Fragaria orientalis (FO) on high-fat diet-induced obese mice was investigated. Drug treatment methods are widely used as obesity treatment methods, but research using various natural products is being conducted due to safety concerns. This study aims to evaluate the anti-obesity effect of FO extract, a natural product derived from Mongolia. Methods : C57BL/6 mice were used and divided into three groups, normal diet group, high-fat diet group, and high-fat diet with FO oral treatment group at a dose of 300 mg/kg. Extract was orally provided everyday for 6 weeks. Body Weight and food intake were measured every 2 days and blood lipid profiles and liver function in the sacrificed mice were evaluated. In addition, protein expression in hepatic tissue and histomorphological changes in liver and adipose tissue were observed. Results : Body weight, adipose tissue weight and FER were significantly lower in a high-fat diet with FO treatment than fed only high-fat diet. There was a significant difference between the high-fat diet and the FO-treated high-fat diet mice. As a result of analyzing lipid metabolism-related genes in hepatic tissue, all of p-AMPK, p-ACC, PPAR-α, CPT-1, and UCP-1 showed significant increases, and PPAR-γ also decreased significantly compared to the high-fat diet group. Conclusion : Overall, these results indicate that FO is effectual in improving obesity, suggesting that it can be used as a possible material for anti-obesity agents or functional supplements for weight control.

A study on clinical efficacy of Abutilon indicum in treatment of bronchial asthma

  • Paranjhape, Archana N;Mehta, Anita A
    • Advances in Traditional Medicine
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    • v.6 no.4
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    • pp.330-335
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    • 2006
  • The present investigation was carried out to determine the efficacy and safety of Abutilon indicum (A. indicum) (Eng: Country Mallow, Fam: Malvaceae) in patients of bronchial asthma. Dried aerial parts of A. indicum were finely powdered and given in the dose of 1 gm tid to 30 patients of either sex in the range of 15 - 80 years with mild to moderate bronchial asthma with or without any concurrent medication. The respiratory functions (FVC, $FEV_{1}$, $FEF_{25-75%}$and MVV) were assessed using a spirometer prior to and after 4 weeks of treatment. Efficacy of the drug in improving clinical symptoms and severity of asthmatic attacks was evaluated by interviewing the patient and by physical and hematological examination at the end of the treatment. 4 weeks treatment with the drug showed statistically significant improvement in various parameters of pulmonary functions in asthmatic subjects. Also significant improvement was observed in clinical symptoms and severity of asthmatic attacks. None of the patient showed any adverse effect with A. indicum. The results of the present study suggest the usefulness of A. indicum in patients with mild to moderate bronchial asthma.

Characterization of the Heavy Metals Contaminating the River Nile at El-Giza Governorate, Egypt and Their Relative Bioaccumulations in Tilapia nilotica

  • Morgan, Ashraf M.; Shin, Ho-Chul;Aty, A.M. Abd El
    • Toxicological Research
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    • v.24 no.4
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    • pp.297-305
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    • 2008
  • This study was carried out to measure the concentration of heavy metals (Pb, Mn, Cr, Cd, Ni, Zn, and Cu) in water and Bolti fish (Tilapia nilotica) samples collected from Rasheed branch of River Nile, north of El-Giza Governorate, Egypt by atomic absorption spectrophotometry. The investigated districts through which the branch passes include El-Manashi, Gezzaya, El Katta, Abo Ghaleb and Wardan. Based on WHO and FAO safety reference standards, the results of the current study showed that water and fish tissues were found to contain heavy metals at significantly variable concentration levels among the investigated districts. They were polluted with respect to all the metals tested at Gezzaya district. However, the levels of analyzed metals in water and fish tissues were found lower than legal limits in other districts. The heavy metals showed differential bioaccumulation in fish tissues of the different districts as the accumulation pattern (as total heavy metal residues) was district dependant as follow: Gezzaya > Wardan > El Katta > Abo Ghaleb > El Manashi.

Antimicrobial Cyclic Peptides for Plant Disease Control

  • Lee, Dong Wan;Kim, Beom Seok
    • The Plant Pathology Journal
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    • v.31 no.1
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    • pp.1-11
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    • 2015
  • Antimicrobial cyclic peptides derived from microbes bind stably with target sites, have a tolerance to hydrolysis by proteases, and a favorable degradability under field conditions, which make them an attractive proposition for use as agricultural fungicides. Antimicrobial cyclic peptides are classified according to the types of bonds within the ring structure; homodetic, heterodetic, and complex cyclic peptides, which in turn reflect diverse physicochemical features. Most antimicrobial cyclic peptides affect the integrity of the cell envelope. This is achieved through direct interaction with the cell membrane or disturbance of the cell wall and membrane component biosynthesis such as chitin, glucan, and sphingolipid. These are specific and selective targets providing reliable activity and safety for non-target organisms. Synthetic cyclic peptides produced through combinatorial chemistry offer an alternative approach to develop antimicrobials for agricultural uses. Those synthesized so far have been studied for antibacterial activity, however, the recent advancements in powerful technologies now promise to provide novel antimicrobial cyclic peptides that are yet to be discovered from natural resources.

Screening of Genetic Polymorphisms of CYP3A4 and CYP3A5 Genes

  • Lee, Jin Sol;Cheong, Hyun Sub;Kim, Lyoung Hyo;Kim, Ji On;Seo, Doo Won;Kim, Young Hoon;Chung, Myeon Woo;Han, Soon Young;Shin, Hyoung Doo
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.6
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    • pp.479-484
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    • 2013
  • Given the CYP3A4 and CYP3A5's impact on the efficacy of drugs, the genetic backgrounds of individuals and populations are regarded as an important factor to be considered in the prescription of personalized medicine. However, genetic studies with Korean population are relatively scarce compared to those with other populations. In this study, we aimed to identify CYP3A4/5 polymorphisms and compare the genotype distributions among five ethnicities. To identify CYP3A4/5 SNPs, we first performed direct sequencing with 288 DNA samples which consisted of 96 Koreans, 48 European-Americans, 48 African-Americans, 48 Han Chinese, and 48 Japanese. The direct sequencing identified 15 novel SNPs, as well as 42 known polymorphisms. We defined the genotype distributions, and compared the allele frequencies among five ethnicities. The results showed that minor allele frequencies of Korean population were similar with those of the Japanese and Han Chinese populations, whereas there were distinct differences from European-Americans or African-Americans. Among the pharmacogenetic markers, frequencies of $CYP3A4^*1B$ (rs2740574) and $CYP3A5^*3C$ (rs776742) in Asian groups were different from those in other populations. In addition, minor allele frequency of $CYP3A4^*18$ (rs28371759) was the highest in Korean population. Additional in silico analysis predicted that two novel non-synonymous SNPs in CYP3A5 (+27256C>T, P389S and +31546T>G, I488S) could alter protein structure. The frequency distributions of the identified polymorphisms in the present study may contribute to the expansion of pharmacogenetic knowledge.

Bosentan and Rifampin Interactions Modulate Influx Transporter and Cytochrome P450 Expression and Activities in Primary Human Hepatocytes

  • Han, Kyoung-Moon;Ahn, Sun-Young;Seo, Hyewon;Yun, Jaesuk;Cha, Hye Jin;Shin, Ji-Soon;Kim, Young-Hoon;Kim, Hyungsoo;Park, Hye-kyung;Lee, Yong-Moon
    • Biomolecules & Therapeutics
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    • v.25 no.3
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    • pp.288-295
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    • 2017
  • The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with $20{\mu}M$ $bosentan+200{\mu}M$ rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.